At the end of every month, the International Myeloma Foundation Newsroom will feature a wrap-up of some of the most fascinating studies about multiple myeloma from medical journals. Here is the October 2024 edition.
The IMF team of medical editors has provided overviews of key studies. Yet, we encourage you to visit the actual articles in the journals for full details and to increase your understanding. Check the IMF Newsroom monthly for updates like this one.
In the Journals (Key Myeloma Research in October 2024)
"Minimally Invasive Assessment of Peripheral Residual Disease During Maintenance or Observation in Transplant-Eligible Patients With Multiple Myeloma"
Source
Marta Lasa et al., Minimally Invasive Assessment of Peripheral Residual Disease During Maintenance or Observation in Transplant-Eligible Patients With Multiple Myeloma. JCO 0, JCO.24.00635 DOI:10.1200/JCO.24.00635 October 1, 2024.
Overview
Clinical trials often report results based on the main goals of the study while other important analyses may take longer to finalize. This abstract focuses on a study involving multiple myeloma (MM), a type of blood cancer, where researchers looked at a less invasive method of monitoring cancer presence in patients after treatment. Instead of testing bone marrow (BM), they evaluated residual disease in the blood, known as peripheral residual disease (PRD), in 138 patients who were eligible for a transplant.
They used advanced techniques to assess PRD and found that 11.5% of patients had positive PRD, which greatly increased their risk of disease progression or death. Specifically, those with positive PRD had a median progression-free survival of just 2.5 months and an overall survival of 47 months. When comparing results, PRD testing proved very reliable in predicting outcomes.
Importantly, patients who showed no detectable PRD had excellent survival rates. The study suggests that monitoring PRD could be a valuable, less invasive tool for identifying patients at higher risk of disease progression during treatment.
"Alliance A061202: ixazomib, pomalidomide, and dexamethasone for patients with lenalidomide-refractory MM in first relapse"
Source
Peter Voorhees, Vera Suman, Yvonne Efebera, Noopur Raje, Sascha Tuchman, Cesar Rodriguez, Jacob Laubach, Misty Bova-Solem, Destin Carlisle, Saad Usmani, Philip McCarthy, Paul G. Richardson; Alliance A061202: ixazomib, pomalidomide, and dexamethasone for patients with lenalidomide-refractory MM in first relapse. Blood Adv 2024; 8 (19): 5039–5050. doi: https://doi.org/10.1182/bloodadvances.2024013623 October 8, 2024.
Overview
A recent study aimed to find the best treatment for patients with multiple myeloma who have not responded to lenalidomide (LEN) and are experiencing their first relapse. Researchers tested a combination of three medications: ixazomib (IXA), pomalidomide (POM), and dexamethasone (DEX). They compared this triplet therapy to a double therapy of POM and DEX alone.
Results showed that the triplet therapy was more effective, with a 63.2% overall response rate (ORR) compared to 43.6% for the double therapy. Patients receiving the triplet also had a significantly better progression-free survival (PFS), lasting an average of 20.3 months, while those on the double therapy averaged 7.5 months.
While more patients on the triplet therapy experienced blood-related side effects, other adverse events were similar between the two groups. The findings suggest that this all-oral triplet therapy should be tested further in larger studies for patients who haven't responded to LEN.
For more information, this trial is registered at www.clinicaltrials.gov (#NCT02004275).
"DNA vaccines against GPRC5D synergize with PD-1 blockade to treat multiple myeloma"
Source
Neeli, P., Maza, P.A.M.A., Chai, D. et al. DNA vaccines against GPRC5D synergize with PD-1 blockade to treat multiple myeloma. npj Vaccines 9, 180 (2024). https://doi.org/10.1038/s41541-024-00979-w October 1, 2024.
Overview
Researchers are exploring new treatment options for multiple myeloma (MM), and one promising target is a receptor called GPRC5D, which is found in high amounts in plasma cells and multiple myeloma. This study tested a combination of a DNA vaccine targeting mouse GPRC5D and PD-1 blockade to see how well it could prevent and treat MM in mice.
The results showed that the vaccine alone could prevent myeloma growth, but it needed PD-1 antibodies to effectively treat existing tumors. The researchers also tested a different version of the vaccine, using a nanoplasmid vector with human GPRC5D, in various mouse tumor models. They found that this approach also stimulated immune responses and inhibited tumor growth.
Overall, these findings suggest that GPRC5D-targeted DNA vaccines could be promising tools for both preventing and treating multiple myeloma.
"Class II ferroptosis inducers are a novel therapeutic approach for t(4;14)-positive multiple myeloma"
Source
Jiasi Zhang, Yuxi Liu, Liping Zuo, Fengjuan Fan, Han Yan, Fei Zhao, Junying Li, Chi Ma, Qun Li, Aoshuang Xu, Jian Xu, Bo Zhang, Yu Hu, Chunyan Sun; Class II ferroptosis inducers are a novel therapeutic approach for t(4;14)-positive multiple myeloma. Blood Adv 2024; 8 (19): 5022–5038. doi: https://doi.org/10.1182/bloodadvances.2023010335 October 8, 2024.
Overview
Multiple myeloma (MM) affects plasma cells, and certain genetic changes, like the t(4;14) abnormality, can lead to worse outcomes for patients. Researchers are exploring a new treatment method called ferroptosis, but how it interacts with these genetic changes in MM has not been well understood.
In this study, researchers found that MM cells with the t(4;14) abnormality are more sensitive to a specific type of ferroptosis-inducing drugs. This increased sensitivity is linked to a protein called MMSET, which helps boost levels of certain fatty acids in the cells. Interestingly, when fatty acids were added to t(4;14)-negative MM cells, they became more sensitive to ferroptosis as well.
Additionally, combining these ferroptosis inducers with bortezomib (a standard treatment for MM) showed stronger anti-cancer effects by reducing key protective molecules in the cells. This combination was effective in lab tests and in animal models.
Overall, these findings suggest that targeting ferroptosis in t(4;14)-positive MM patients could be a promising new treatment strategy to improve their outcomes.
"A.R.R.O.W.2: once- vs twice-weekly carfilzomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma"
Source
Meletios A. Dimopoulos, Daniel Coriu, Sosana Delimpasi, Ivan Špička, Terry Upchurch, Belle Fang, Rakhshandra Talpur, Edward Faber, Meral Beksac, Xavier Leleu; A.R.R.O.W.2: once- vs twice-weekly carfilzomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma. Blood Adv 2024; 8 (19): 5012–5021. doi: https://doi.org/10.1182/bloodadvances.2024013101 October 8, 2024.
Overview
A recent phase 3 study compared two treatment schedules for relapsed or refractory multiple myeloma (RRMM): once-weekly carfilzomib (56 mg/m²) combined with lenalidomide and dexamethasone (KRd56) versus the standard twice-weekly carfilzomib (27 mg/m²) (KRd27). The goal was to see if the once-weekly treatment was as effective as the twice-weekly regimen.
The study included 454 patients who were randomly assigned to either treatment group. Results showed that the overall response rate (ORR) was 82.5% for the once-weekly group and 86.3% for the twice-weekly group. Although the once-weekly treatment did not statistically prove to be as effective as the twice-weekly regimen, it still showed promising results, with a higher complete response (CR) rate of 46.9% compared to 36.3% in the twice-weekly group.
Both treatment options had similar safety profiles, and progression-free survival rates were comparable as well. While the once-weekly treatment didn't meet the statistical threshold for being noninferior, it offers a convenient option for patients with RRMM.
For more details, this trial is registered at www.ClinicalTrials.gov (#NCT03859427).
"Real-world treatment patterns and outcomes in relapsed/refractory multiple myeloma (1-3 prior lines): Flatiron database"
Source
Binod Dhakal, Hermann Einsele, Jordan M. Schecter, William Deraedt, Nikoletta Lendvai, Ana Slaughter, Carolina Lonardi, Sandhya Nair, Jianming He, Akshay Kharat, Patricia Cost, Satish Valluri, Kwee Yong; Real-world treatment patterns and outcomes in relapsed/refractory multiple myeloma (1-3 prior lines): Flatiron database. Blood Adv 2024; 8 (19): 5062–5071. doi: https://doi.org/10.1182/bloodadvances.2024012640 October 8, 2024.
Overview
A recent study looked at patients with multiple myeloma (MM) who have become resistant to lenalidomide after receiving one to three lines of treatment. Researchers analyzed data from 12,767 patients between January 2016 and April 2022, focusing on 1,455 who met the criteria.
The study found that the most common next treatments were combination therapies, with daratumumab, pomalidomide, and dexamethasone being the most frequently used. The median progression-free survival (RW-PFS) was 6.5 months, and overall survival (OS) was 44.4 months. The RW-PFS was similar regardless of how many previous treatments patients had received.
Certain factors, like having advanced disease, poor performance status, low hemoglobin levels, high-risk genetic changes, and being resistant to anti-CD38 antibody treatments, were linked to worse survival outcomes.
Importantly, the study revealed that a high attrition rate occurred among patients with just one prior treatment, with 85% moving from the second to the fifth line of treatment. This included 25% of patients who died and 60% who did not receive any further treatment.
Overall, the findings highlight that patients with lenalidomide-refractory MM face poor outcomes and quickly exhaust available therapies, underscoring the urgent need for more effective early treatments.
"Soluble SLAMF7 is generated by alternative splicing in multiple myeloma cell"
Source
Kikuchi J, Hori M, Osada N, Matsuoka S, Suzuki A, Kakugawa S, Yasui H, Harada T, Tenshin H, Abe M, Nakasone H, Furukawa Y. Soluble SLAMF7 is generated by alternative splicing in multiple myeloma cells. Haematologica 2024;109(10):3414-3418; https://doi.org/10.3324/haematol.2024.285368. October, 2024.
Overview
Multiple myeloma (MM) affects plasma cells, and while new treatments like the anti-CD38 antibody daratumumab have improved survival rates, many patients still face relapses. One factor contributing to this issue is the gain of chromosome 1q, which is found in a significant number of patients and is linked to drug resistance and poor outcomes.
A specific protein called SLAMF7, found on MM cells and located on chromosome 1q, may play a role in the disease's progression. This protein can exist in a soluble form (sSLAMF7) in the blood, and higher levels of sSLAMF7 are associated with worse prognosis. The study suggests that sSLAMF7 is produced from a special variant of the SLAMF7 gene that lacks a part needed to anchor it to the cell membrane.
Researchers found that sSLAMF7 might promote the growth of certain immune cells, which can lead to immune suppression in MM patients. This could explain why treatments like elotuzumab, which neutralizes sSLAMF7, might help improve immune function in these patients.
Overall, the findings indicate that monitoring sSLAMF7 levels could be valuable for predicting how patients will respond to treatments like elotuzumab. The study suggests further research is needed to explore the link between this protein and disease progression, as well as its potential as a biomarker for treatment response.
"Aberrant NSUN2-mediated m5C modification of exosomal LncRNA MALAT1 induced RANKL-mediated bone destruction in multiple myeloma"
Source
Yu, M., Cai, Z., Zhang, J. et al. Aberrant NSUN2-mediated m5C modification of exosomal LncRNA MALAT1 induced RANKL-mediated bone destruction in multiple myeloma. Commun Biol 7, 1249 (2024). https://doi.org/10.1038/s42003-024-06918-8 October 2, 2024.
Overview
Researchers have been exploring how communication between multiple myeloma (MM) cells and osteoclasts (OCs) affects bone damage in patients. This study focused on a long non-coding RNA called MALAT1, which is influenced by two proteins, NSUN2 and YBX1. These proteins help increase MALAT1 levels in MM cells, allowing it to be carried to osteoclasts through tiny vesicles called exosomes.
To understand this process, the researchers used various techniques, including RNA sequencing and staining to analyze bone changes. They found that MALAT1 was the most abundant long non-coding RNA in the exosomes of MM cells and could promote the development of osteoclasts by enhancing RANKL expression and activating specific signaling pathways.
Additionally, NSUN2 modifies MALAT1, helping to stabilize it with the help of YBX1. Clinical data showed that higher levels of MALAT1, NSUN2, and YBX1 were linked to greater bone destruction and increased RANKL expression.
Overall, this study highlights the role of MALAT1 in the communication between MM cells and osteoclasts, suggesting it may contribute to bone lesions in multiple myeloma.
"KDM6A regulates immune response genes in multiple myeloma"
Source
Daphné Dupéré-Richer, Alberto Riva, Benjamin G. Barwick, Sayantan Maji, Heidi Casellas Román, Jianping Li, Umasankar De, Amin Sobh, Gabrielle Quickstad, Crissandra Piper, Marta Kulis, Teresa Ezponda, José Ignacio Martín-Subero, Giovanni Tonon, Weizhou Zhang, Constantine S. Mitsiades, Lawrence H. Boise, Richard L. Bennett, Jonathan D. Licht; KDM6A regulates immune response genes in multiple myeloma. Blood 2024; 144 (14): 1508–1520. doi: https://doi.org/10.1182/blood.2024024518 October 3, 2024.
Overview
KDM6A, a tumor suppressor, plays a crucial role in multiple cancers, including multiple myeloma (MM). Researchers studied MM cells with disrupted KDM6A to understand its effects. They found that KDM6A helps activate genes important for immune response, particularly NLRC5 and CIITA, which regulate key immune system genes. In MM patients with low KDM6A levels, these genes are less active. When KDM6A is lost, certain markers on DNA change, leading to reduced gene activity. However, using an HDAC3 inhibitor can restore some immune functions. In a mouse model, losing KDM6A increased tumor growth and reduced T-cell activity, suggesting it may weaken the immune system’s ability to fight cancer.
"KDM6A controls immunogenicity in Multiple Myeloma"
Source
Jerome Moreaux; KDM6A controls immunogenicity in MM. Blood 2024; 144 (14): 1465–1467. doi: https://doi.org/10.1182/blood.2024026013 October 3, 2024.
Overview
Researchers found that the enzyme KDM6A plays a crucial role in regulating the immune response in multiple myeloma (MM). KDM6A helps activate genes involved in immune recognition and controls how MM cells interact with the immune system. When KDM6A is lost, the immune system is less able to recognize and attack cancer cells. This loss also leads to changes in gene expression, making it harder for immune cells to infiltrate the tumor.
Using gene-editing techniques, the scientists discovered that cells without KDM6A showed reduced expression of key immune markers, including major histocompatibility complex (MHC) genes, which help the immune system identify threats. However, treating these KDM6A-deficient cells with an HDAC3 inhibitor restored immune function by reactivating these important genes. This treatment also increased the activity of certain immune signaling pathways, suggesting a potential therapeutic approach.
In animal studies, tumors without KDM6A grew larger and attracted fewer immune cells. The research points to KDM6A as an important player in immune system suppression in MM and suggests that targeting it could enhance immune responses and improve treatment outcomes for patients with KDM6A deficiency.
"In vitro models of the crosstalk between multiple myeloma and stromal cells recapitulate the mild NF-κB activation observed in vivo"
Source
Colombo, F., Guzzeloni, V., Kizilirmak, C. et al. In vitro models of the crosstalk between multiple myeloma and stromal cells recapitulate the mild NF-κB activation observed in vivo. Cell Death Dis 15, 731 (2024). https://doi.org/10.1038/s41419-024-07038-1 October 6, 2024.
Overview
In multiple myeloma (MM), the NF-κB pathway is linked to cancer growth, but its activation is not uniform across all cancer cells. By studying bone marrow samples, researchers found that only a small number of MM cells show strong NF-κB activity. To better understand this, they used advanced imaging and 3D models to mimic how MM cells interact with the bone marrow environment and other cells, like mesenchymal stromal cells (MSCs).
Their findings showed that:
- Interactions between MM cells, MSCs, and the bone marrow structure influence inflammation.
- The cytokine IL-1β, which is common in MM patients, activates MSCs, leading to stronger NF-κB activity in some MM cells
- Inhibiting IL-1β with the drug Anakinra can reduce NF-κB activation.
Overall, NF-κB activation in MM is limited to a small number of cells and is influenced by both the surrounding environment and signals from other cells in the bone marrow.
"Leukaemia, lymphoma, and multiple myeloma mortality after low-level exposure to ionising radiation in nuclear workers (INWORKS): updated findings from an international cohort study"
Source
Leuraud, Klervi et al. Leukaemia, lymphoma, and multiple myeloma mortality after low-level exposure to ionising radiation in nuclear workers (INWORKS): updated findings from an international cohort study. The Lancet Haematology, Volume 11, Issue 10, e761 - e769, October 2024.
Overview
This study, part of the International Nuclear Workers Study (INWORKS), looked at how exposure to low-dose ionizing radiation affects the risk of death from blood cancers in nuclear workers. The study involved over 309,000 workers from nuclear facilities in France, the UK, and the USA, who were monitored for radiation exposure between 1944 and 2016.
The researchers found a clear link between radiation exposure and deaths from certain types of leukemia, especially chronic myeloid leukemia and myelodysplastic syndromes. They also observed a positive association with multiple myeloma but found no significant link with other blood cancers like non-Hodgkin lymphoma or chronic lymphocytic leukemia (CLL).
Although the workers in the study had relatively low radiation exposure, the findings show that even small doses can slightly increase the risk of leukemia. These results are important for shaping radiation safety guidelines and protecting workers in radiation-related jobs.
"Discontinuation of maintenance therapy in multiple myeloma guided by multimodal measurable residual disease negativity (MRD2STOP)"
Source
Derman, B.A., Major, A., Cooperrider, J. et al. Discontinuation of maintenance therapy in multiple myeloma guided by multimodal measurable residual disease negativity (MRD2STOP). Blood Cancer J. 14, 170 (2024). https://doi.org/10.1038/s41408-024-01156-x October 7, 2024..
Overview
The MRD2STOP trial studied whether maintenance therapy in multiple myeloma (MM) can be safely stopped based on undetectable measurable residual disease (MRD). Patients in the trial had MRD levels below 10⁻⁵ and had been on maintenance therapy for at least a year. They were confirmed to have no detectable disease using PET scans, bone marrow tests, and a highly sensitive test called clonoSEQ, which can detect MRD at levels as low as 10⁻⁷.
The trial included 47 patients who stopped their maintenance therapy after a median of 36 months. Results showed that patients with MRD levels below 10⁻⁷ had a lower chance of the disease coming back. Over three years, only 20% of these patients experienced disease resurgence, compared to 75% for those with MRD levels at or above 10⁻⁷.
Overall, stopping maintenance therapy in patients with MRD below 10⁻⁶ led to low relapse rates, but the study suggests that using 10⁻⁷ as the threshold might be even better for deciding when to stop treatment. More research is needed to confirm these findings.
"Single-cell analysis of the multiple myeloma microenvironment after gamma-secretase inhibition and CAR T-cell therapy."
Source
David G Coffey, Pinar Ataca Atilla, Erden Atilla, Ola Landgren, Andrew J Cowan, Sylvain Simon, Margot Pont, Melissa L. Comstock, Geoffrey R Hill, Stanley R. Riddell, Damian J Green; Single-cell analysis of the multiple myeloma microenvironment after gamma-secretase inhibition and CAR T-cell therapy. Blood 2024; blood.2024025231. doi: https://doi.org/10.1182/blood.2024025231 October 7, 2024.
Overview
CAR T-cells and bispecific antibodies (BsAb) targeting BCMA have improved treatment for relapsed and refractory multiple myeloma (MM), but resistance to these therapies is still a big challenge. One known resistance mechanism is BCMA shedding by an enzyme called gamma-secretase. Blocking this enzyme might enhance the effectiveness of anti-BCMA therapies.
In a phase I trial, researchers tested a gamma-secretase inhibitor (GSI) called crenigacestat with anti-BCMA CAR T-cells (FCARH143). They used advanced techniques to study the effects of GSI on the tumor environment. The most noticeable changes occurred in monocytes, immune cells that can help tumors grow. The GSI reduced certain types of monocytes and caused changes in gene expression and how DNA is accessed, which affected how cells communicate.
Interestingly, some patients had a genetic change—a deletion in the BCMA gene—that was linked to shorter progression-free survival (57 days vs. 861 days). This deletion happened in patients previously treated with anti-BCMA therapies.
Overall, GSIs are being studied alongside other BCMA-targeting treatments, and this research provides valuable insights into how GSI affects both tumor and immune cells. These findings may help improve BCMA-directed therapies.
"When Chinese patients with plasma cell disorders encountered the nationwide Omicron outbreak (December 2022): a real-world multicenter and multiregional study"
Source
Jiang, X., Han, X., Jin, F., An, G., Hou, J., He, J., … cai, zhen. (2024). When Chinese patients with plasma cell disorders encountered the nationwide Omicron outbreak (December 2022): a real-world multicenter and multiregional study. Hematology, 29(1). https://doi.org/10.1080/16078454.2024.2411741 October 7, 2024.
Overview
This study looked at the impact of the Omicron outbreak in December 2022 on Chinese patients with plasma cell disorders (PCD). The researchers focused on how COVID-19 affected these patients and identified risk factors for severe illness and hospitalization.
They studied 404 PCD patients, 342 of whom had COVID-19. Among the infected, 16% had severe cases, and 2 patients (0.7%) died, while 83% recovered. Older age (over 65) and recent treatment with anti-CD38 monoclonal antibodies increased the risk of severe COVID-19. Patients who had CAR-T therapy within six months had a higher risk of being hospitalized and took longer to recover.
Interestingly, vaccination did not seem to protect against infection or severe cases. The study shows that PCD patients, especially those who recently had certain treatments, are more vulnerable to severe COVID-19 and need special protection during outbreaks.
"Redefining chimeric antigen receptor T-cell (CAR-T) regulation: China’s responses to address secondary cancer risks of CAR-T therapy"
Source
Tan, R., Li, R., Dai, MY. et al. Redefining chimeric antigen receptor T-cell (CAR-T) regulation: China’s responses to address secondary cancer risks of CAR-T therapy. J Hematol Oncol 17, 90 (2024). https://doi.org/10.1186/s13045-024-01602-0 October 8, 2024.
Overview
CAR-T therapy has revolutionized cancer treatment since its first FDA approval in 2017. China has made rapid strides in developing CAR-T therapies, thanks to major investments. However, these treatments are expensive and not covered by basic medical insurance.
In November 2023, the FDA raised concerns about the risk of secondary cancers linked to CAR-T therapy, prompting global attention. China's National Medical Products Administration (NMPA) had already addressed these concerns by requiring lifelong monitoring of patients and emphasizing safety. However, more regulations are needed to tackle emerging risks. The authors suggest stricter standards for drug approval and better reporting systems to ensure the safe growth of the CAR-T industry in China.
"Phase II study of novel CXCR2 agonist and Plerixafor for rapid stem cell mobilization in patients with multiple myeloma"
Source
Sidana, S., Bankova, A.K., Hosoya, H. et al. Phase II study of novel CXCR2 agonist and Plerixafor for rapid stem cell mobilization in patients with multiple myeloma. Blood Cancer J. 14, 173 (2024). https://doi.org/10.1038/s41408-024-01152-1 October 9, 2024.
Overview
A phase 2 trial tested the combination of MGTA-145 and plerixafor to mobilize hematopoietic stem cells (HSCs) in 25 multiple myeloma patients. Most patients had previously received lenalidomide (92%) and an anti-CD38 antibody (24%). After plerixafor and MGTA-145 were given, 88% of patients successfully collected enough HSCs in two days or less, and 68% did so in just one day.
Mild side effects, like grade 1 pain, occurred in 60% of patients. All 19 patients who received a transplant with these mobilized HSCs had successful and durable engraftment by day 100. Most transplants (74%) were minimal residual disease-negative, and the HSC and immune cell makeup was similar to that of patients using traditional methods.
"Deep hematologic response to RD treatment in patients with multiple myeloma is associated with overexpression of IL-17R in CD138+ plasma cells"
Source
Kulig, P., Łuczkowska, K., Machaliński, B. et al. Deep hematologic response to RD treatment in patients with multiple myeloma is associated with overexpression of IL-17R in CD138+ plasma cells. Sci Rep 14, 23559 (2024). https://doi.org/10.1038/s41598-024-74558-3 October 9, 2024.
Overview
Lenalidomide (LEN) is a widely used immunomodulatory drug for multiple myeloma (MM), but many patients eventually become resistant and relapse. This study aimed to identify molecular pathways linked to a good and lasting response to LEN. Researchers looked at newly diagnosed MM patients and those receiving LEN and dexamethasone (RD) as first-line treatment who achieved at least a very good partial remission (VGPR).
They isolated RNA from MM cells and performed advanced sequencing, validating their findings with additional tests. The results showed a significant increase in gene expression in the RD group compared to newly diagnosed patients, indicating the role of epigenetic mechanisms. They also found that genes involved in interactions within the MM environment and immune response were upregulated. Notably, the gene for the IL-17 receptor was overexpressed in the RD group, which could be targeted in future treatments.
Understanding the molecular factors behind strong responses to LEN could lead to improved treatment strategies and the development of additional therapies to enhance its effectiveness against MM.
"Radiotherapy for haematological malignancies"
Source
Dee, Edward Christopher et al. Radiotherapy for haematological malignancies. The Lancet Haematology, Volume 11, Issue 10, e721 - e722 October 2024.
Overview
Radiotherapy for blood cancers has changed significantly in recent years due to better imaging, advanced radiation technology, and improved understanding of these diseases. These advancements have made radiation treatments more effective and safer, allowing for more personalized care. In an overview in *The Lancet Haematology*, Lena Specht discusses these improvements and the challenges that remain, such as concerns about past side effects and how to integrate radiation with new systemic treatments.
Globally, the incidence of blood cancers is rising. In 2019, there were over 155,000 new cases of multiple myeloma and more than 640,000 cases of leukemia, a significant increase from 1990. This trend highlights the growing need for effective and affordable treatment, especially as populations age and more young people are at risk for rare blood cancers. Short-course radiation has proven to be less toxic and more cost-effective for treating indolent lymphomas, yet it is still underutilized, even in wealthy countries like the USA.
Interestingly, the lower doses of radiation needed for many blood cancers mean treatment can be effective even in areas lacking advanced technology. In regions where modern therapies like stem cell transplants are not available, radiation becomes essential for managing advanced disease. However, access to radiation therapy remains a major issue; globally, only 40-60% of patients who need it can receive it, with up to 90% of patients in low-income areas lacking access.
To address these challenges, there is a need for global collaboration to increase access to radiation therapy and reduce fears about its side effects. Existing radiation techniques can be effective and safe, even in resource-limited settings. By working together, radiation oncologists and medical oncologists can help patients make informed treatment decisions that balance effectiveness with safety.
Investment in radiation therapy infrastructure and training is crucial, as it can lead to significant economic benefits and improve outcomes for patients with potentially curable blood cancers. Furthermore, international collaboration, such as initiatives from the International Lymphoma Radiation Oncology Group, can help share knowledge and promote better access to radiation treatments worldwide.
"Exposure-response relationships of venetoclax in combination with carfilzomib and dexamethasone in relapsed/refractory t(11;14) multiple myeloma patients"
Source
Badawi, M.A., Engelhardt, B., Dobkowska, E. et al. Exposure-response relationships of venetoclax in combination with carfilzomib and dexamethasone in relapsed/refractory t(11;14) multiple myeloma patients. Invest New Drugs (2024). https://doi.org/10.1007/s10637-024-01471-x October 10, 2024.
Overview
Venetoclax is a new type of drug that blocks a protein called BCL-2 and is being studied for treating a specific type of multiple myeloma (MM) known as t(11;14). This study aimed to understand how effective and safe venetoclax is when used with carfilzomib and dexamethasone in patients whose MM has come back or did not respond to previous treatments.
Fifty-seven patients participated in the analysis, receiving either the combination treatment (VenKd) or a control treatment (Kd). The researchers looked at how long patients remained free from disease progression and their response rates, including overall response and higher levels of response.
The results showed that adding venetoclax to the treatment led to better response rates compared to the control group. Specifically, patients taking venetoclax had higher rates of overall response and very good partial responses. However, while higher doses of venetoclax were linked to better complete response rates, no clear connection was found between venetoclax exposure and overall or very good responses.
Both the 400 mg and 800 mg doses of venetoclax were generally well-tolerated, but there was a higher incidence of severe low white blood cell counts (neutropenia) with increased doses. Importantly, higher doses did not lead to more severe side effects or serious infections.
These findings confirm that adding venetoclax to carfilzomib and dexamethasone is beneficial for patients with t(11;14) positive relapsed or refractory multiple myeloma, supporting further studies of venetoclax at doses of 400 to 800 mg daily.
"Selection determines therapeutic effects: a retrospective analysis of the application of different frailty tools in elderly patients with multiple myeloma"
Source
Li, Y., Zhao, S., Xu, J. et al. Selection determines therapeutic effects: a retrospective analysis of the application of different frailty tools in elderly patients with multiple myeloma. Discov Onc 15, 546 (2024). https://doi.org/10.1007/s12672-024-01305-5 October 10, 2024
Overview
This study examined the effectiveness of four frailty assessment tools—the International Myeloma Working Group Frailty Index (IMWG-FI), Mayo Score, UK Myeloma Research Alliance Risk Profile (MRP), and Intergroupe Francophone du Myélome (IFM) simplified frailty scale—in classifying frailty in elderly patients with multiple myeloma (MM). Eighty-four newly diagnosed MM patients aged 60 and older from HeBei University Hospital were evaluated using these tools. The researchers found that 64 patients (76.2%) were identified as frail by at least one tool, but overall consistency among the assessments was low, although the IMWG-FI and MRP showed moderate agreement.
Survival analysis revealed that frail patients identified by the IMWG-FI, Mayo Score, and MRP had significantly lower overall survival and progression-free survival compared to non-frail patients. However, there was no significant difference in survival rates among frail patients identified by the different tools. The study concludes that combining the IMWG-FI and MRP may help reduce subjectivity and improve the identification of frail patients, providing a clearer understanding of frailty in elderly individuals with multiple myeloma.
"Kidney function in newly diagnosed myeloma patients: factors associated with kidney impairment and recovery"
Source
Cesar, B.N., Braga, W.M.T., Hamerschlak, N. et al. Kidney function in newly diagnosed myeloma patients: factors associated with kidney impairment and recovery. BMC Nephrol 25, 344 (2024). https://doi.org/10.1186/s12882-024-03717-5 October 11, 2024.
Overview
This study looked at the kidney function of 167 patients with multiple myeloma (MM) who developed kidney problems during their first year of treatment. The patients were treated at two hospitals between January 2009 and January 2019. Those with pre-existing kidney disease or on dialysis before their MM diagnosis were excluded. The average age of the patients was 66, and many had high blood pressure. A significant number were at higher risk according to the International Staging System, with nearly half having an estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m² at diagnosis.
After 12 months, only 4 patients (2.3%) required dialysis, and 18 patients (10.7%) passed away. The study found that factors like anemia, high uric acid levels, and high protein in urine were linked to worse kidney function. However, better kidney recovery at 12 months was significantly associated with having a higher eGFR at diagnosis and undergoing hematopoietic stem cell transplantation (HSCT). Overall, the findings highlight the importance of monitoring kidney health in multiple myeloma patients and the potential benefits of early treatment strategies.
"Construction and validation of a prognostic model of angiogenesis-related genes in multiple myeloma"
Source
Hu, R., Chen, F., Yu, X. et al. Construction and validation of a prognostic model of angiogenesis-related genes in multiple myeloma. BMC Cancer 24, 1269 (2024). https://doi.org/10.1186/s12885-024-13024-9 October 11, 2024.
Overview
This study explored the role of angiogenesis-related genes (ARGs) in multiple myeloma (MM) to create a new model for predicting patient outcomes. Researchers analyzed data from various public databases, including the MMRF-CoMMpass cohort and other gene expression datasets, to identify genes that are differentially expressed in tumors compared to healthy tissue. They used advanced statistical methods to find and analyze these genes, ultimately identifying 898 differentially expressed genes (DEGs) and narrowing this down to 24 ARGs that showed significant changes related to MM.
From these ARGs, the team selected three key prognostic genes—AKAP12, C11orf80, and EMP1—to construct a risk model that categorizes patients into high- and low-risk groups based on their median risk score. This model was validated using additional patient data and linked to various clinical factors. The study found that certain immune cells, like memory B cells, were more common in high-risk patients, while immature B cells were more prevalent in low-risk patients. The researchers also identified specific microRNAs associated with the prognostic genes. Overall, the study developed and validated a new prognostic model that enhances the understanding of how angiogenesis is connected to multiple myeloma, potentially guiding future treatment strategies.
"Deciphering MARCH5’s Impact on Multiple Myeloma: Insights into Autophagy Regulation and AKT-FOXO3 Signaling"
Source
Hamed Bashiri, Ahad Khalilnezhad, Haruhito Totani, Joe Yeong, Tae-Hoon Chung, Felicia Wee, Yuezhen Xue, Zhen Wei Neo, Li Yen Chong, Wee Joo Chng, Atsushi Watanabe, Siok-Bian Ng, The Phyu, Toshio Suda; Deciphering MARCH5’s Impact on Multiple Myeloma: Insights into Autophagy Regulation and AKT-FOXO3 Signaling. Blood Neoplasia 2024; 100046. doi: https://doi.org/10.1016/j.bneo.2024.100046 October 12, 2024
Overview
In this study, researchers focused on how myeloma cells survive by producing excess immunoglobulins (Ig), which create toxic protein buildups. They found that autophagy, a process that helps cells break down and remove these toxic proteins, is essential for the survival of myeloma cells. The study particularly examined a protein called membrane-associated RING finger protein 5 (MARCH5), which is involved in regulating autophagy and is located on the outer membrane of mitochondria.
The researchers used various datasets, including the Cancer Dependency Map and clinical data from the CoMMpass and HOVON studies, to investigate MARCH5's role in multiple myeloma (MM). They discovered that high levels of MARCH5 were linked to better patient outcomes. When MARCH5 was "knocked down" or reduced in myeloma cells, those cells showed significantly decreased viability and autophagic activity. They also uncovered a new pathway involving MARCH5, AKT, and FOXO3, where MARCH5 helps regulate autophagy through the AKT-mediated degradation of FOXO3. Reducing FOXO3 levels had similar effects on cell viability, confirming FOXO3’s important role in this process. Overall, this research highlights the critical role of MARCH5 in multiple myeloma and lays the groundwork for developing targeted therapies that could improve treatment outcomes.
"Functional variant rs9344 at 11q13.3 regulates CCND1 expression in multiple myeloma with t(11;14)"
Source
Werly, A., Hampel, M., Hielscher, T. et al. Patterns of progression in a contemporary cohort of 447 patients with smoldering multiple myeloma. Blood Cancer J. 14, 176 (2024). https://doi.org/10.1038/s41408-024-01159-8 October 14, 2024.
Overview
Smoldering multiple myeloma (SMM) is an early form of multiple myeloma (MM), where patients usually don’t show symptoms. However, SMM can progress to MM, and understanding this progression is essential for determining when to start treatment. Monitoring SMM involves looking at factors like the number of abnormal plasma cells in the bone marrow, levels of a specific protein in the blood, and any genetic abnormalities.
Current research shows that treating high-risk SMM early can lead to better outcomes, but this approach is not yet the standard care. Recent updates to MM diagnostic criteria allow doctors to treat patients based on specific disease markers before serious organ damage occurs, which could help prevent complications.
A study from the Mayo Clinic investigated the progression of SMM in 406 patients, revealing that bone damage and anemia were the most common problems in those at high risk. In a new study from Heidelberg University Hospital involving 447 SMM patients, researchers found similar trends, with most patients progressing to MM due to disease markers rather than significant organ damage. The results showed that a large number of patients progressed with only disease markers and no major health issues.
This research emphasizes the need for ongoing monitoring, particularly using imaging techniques like MRI to catch bone damage early. Many patients with SMM only show biomarkers of progression, which highlights the importance of identifying the right time to start treatment to avoid overtreatment and prevent further complications.
While this study supports earlier findings about SMM progression, it underscores the need for improved diagnostic methods to catch more cases before patients experience serious health issues. Frequent imaging, especially for high-risk patients, could play a vital role in managing SMM effectively.
"Inhibition of MICA and MICB shedding enhances memory-like NK-cell–mediated cytotoxicity against multiple myeloma"
Source
Sabrin Tahri, Sara Piccinelli, Nang Kham Su, Luisa Lampe, Han Dong, Juliana Vergara Cadavid, Rebecca Boiarsky, Natalie Papazian, Elizabeth D. Lightbody, Amanda Cao, Jean-Baptiste Alberge, Lucas Ferrari de Andrade, Mahshid Rahmat, Yujia Shen, Laura Blanco Fernández, Aintzane Zabaleta, Andreas Günther, Gad Getz, Pieter Sonneveld, Tom Cupedo, Kai W. Wucherpfennig, Irene M. Ghobrial, Rizwan Romee; Inhibition of MICA and MICB shedding enhances memory-like NK-cell–mediated cytotoxicity against multiple myeloma. Blood Adv 2024; 8 (20): 5365–5370. doi: https://doi.org/10.1182/bloodadvances.2023010869 October 22, 2024
Overview
One of the key challenges in treating multiple myeloma (MM) is how it interacts with the bone marrow environment, making immunotherapies less effective over time as patients develop resistance or do not respond at all.
Natural killer (NK) cells, part of the immune system, are crucial in attacking tumor cells, but in MM, these cells often become dysfunctional, losing their ability to fight the cancer. Scientists are exploring ways to boost NK cell activity by using a type of NK cell called “memory-like” NK cells. These cells have shown promise in fighting other cancers, but have not yet been studied in MM.
Researchers are focusing on a protein called MICA/B, which is found on the surface of MM cells and helps NK cells recognize and attack them. However, MM cells can shed this protein, making it harder for NK cells to detect them. A new antibody called 7C6 has been developed to prevent MICA/B from being shed, allowing NK cells to better recognize and kill MM cells.
In lab studies, the 7C6 antibody increased NK cell activity against MM cells. When memory-like NK cells were combined with the 7C6 antibody, they became even more effective at destroying MM cells. Early tests in mice also showed that this combination helped control the growth of MM tumors, although more research is needed to improve overall survival outcomes.
This approach could lead to new immunotherapies for MM, using a combination of memory-like NK cells and the 7C6 antibody to enhance the immune system's ability to fight the disease.
"Patient preferences for intervention in the setting of precursor multiple myeloma"
Source
Marinac, C.R., Downey, K., Perry, J. et al. Patient preferences for intervention in the setting of precursor multiple myeloma. Blood Cancer J. 14, 175 (2024). https://doi.org/10.1038/s41408-024-01161-0 October 14, 2024.
Overview
Multiple myeloma (MM) typically develops from earlier conditions like monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). These precursor conditions increase the risk of progressing to MM, which can be between 1% and 10% each year. In some cases, this risk is even higher. Currently, the main approach for managing MGUS and SMM is "watchful waiting," where patients are monitored until their condition worsens, making it difficult to treat effectively. This can lead to significant anxiety and reduced quality of life, even for those with mild symptoms.
Researchers are exploring whether treatments can help prevent the progression from these precursor conditions to full-blown MM. While early treatments show promise, they also come with risks, such as fatigue and potential long-term side effects, leading many doctors to hesitate in recommending them. Alternative approaches, like dietary changes, are being studied, but they may not be as effective as direct cancer treatments.
To better understand what patients want in terms of treatment, a survey was developed to assess their preferences regarding interventions for MGUS and SMM. Participants were presented with different scenarios involving factors such as the likelihood of preventing MM, costs, personal inconvenience, and risk of side effects. The study involved 272 participants, mostly well-educated and aged around 64.
The results indicated that patients strongly preferred treatments that offered a higher chance of preventing MM and minimizing side effects, although a significant number also valued low costs and personal convenience. Interestingly, there were distinct groups of patients based on their preferences: some prioritized preventing MM, while others focused on avoiding side effects or minimizing costs.
The findings highlight that patient preferences are varied, emphasizing the need for diverse treatment options. However, the study does have limitations, including a sample that may not fully represent the broader population of patients with MGUS and SMM. Future research should further explore how various risks influence patient choices and the balance between active monitoring and intervention strategies.
While there have been advancements in treatments for MM precursor diseases, no curative options exist yet. Understanding patient preferences is crucial to developing effective treatment strategies that meet the needs of this unique group.
"Predictors of Response to Venetoclax and Therapeutic Potential of CDK7 Inhibition in Multiple Myeloma"
Source
Rudra P. Dutta, Santiago Thibaud, Violetta Leshchenko, Meghana Ram, David T. Melnekoff, Sherry Bhalla, Paula Restrepo, Vikas A. Gupta, Benjamin G. Barwick, Scott Newman, Jonathan McCafferty, Feras Hantash, Ajay K. Nooka, Hearn J. Cho, Shambavi Richard, Cesar Rodriguez, Adriana Rossi, Larysa Sanchez, Ajai Chari, Lawrence H. Boise, Sundar Jagannath, Joshua Richter, Samir Parekh, Alessandro Laganà; Predictors of Response to Venetoclax and Therapeutic Potential of CDK7 Inhibition in Multiple Myeloma. Blood Neoplasia 2024; 100049. doi: https://doi.org/10.1016/j.bneo.2024.100049 October 14, 2024
Overview
Venetoclax is a drug that targets the BCL2 protein and has shown promise in treating multiple myeloma (MM), especially in patients with the t(11;14) gene change. In this study, researchers aimed to find markers that predict how well patients respond to venetoclax. By analyzing data from patients with relapsed or hard-to-treat MM who were treated with venetoclax (alone or with other drugs), they discovered a six-gene signature that could group patients by their risk of relapse.
The study also found that patients with a gain in chromosome 1q, which includes the MCL1 gene, had worse progression-free survival, even if they had the t(11;14) gene change. Since MCL1 is known to cause resistance to venetoclax, the researchers tested whether blocking a protein called CDK7 could help. Lab experiments showed that reducing CDK7 lowered MCL1 levels and made MM cells more sensitive to venetoclax. Combining a CDK7 inhibitor (THZ1) with venetoclax also increased cell death in MM cells that were resistant to venetoclax due to 1q gain.
These findings suggest that using venetoclax with CDK7 inhibitors could be a better treatment strategy for patients with MM, especially those with the 1q gain.
"Genomic instability and genetic heterogeneity in aging: insights from clonal hematopoiesis (CHIP), monoclonal gammopathy (MGUS), and monoclonal B-cell lymphocytosis (MBL)"
Source
Kallai, A., Ungvari, Z., Fekete, M. et al. Genomic instability and genetic heterogeneity in aging: insights from clonal hematopoiesis (CHIP), monoclonal gammopathy (MGUS), and monoclonal B-cell lymphocytosis (MBL). GeroScience (2024). https://doi.org/10.1007/s11357-024-01374-y October 15, 2024.
Overview
Aging is a complex process that leads to a decline in body functions and a higher risk of chronic diseases. One of the key factors behind aging is genomic instability, which causes genetic changes and mutations in cells. This review looks at how genomic instability affects the blood system, focusing on three conditions common in older adults: clonal hematopoiesis of indeterminate potential (CHIP), monoclonal gammopathy of undetermined significance (MGUS), and monoclonal B-cell lymphocytosis (MBL).
- CHIP: This happens when stem cells in the blood start multiplying due to mutations.
- MGUS: Involves abnormal plasma cells that produce a type of protein called monoclonal immunoglobulins.
- MBL: Refers to the growth of clonal B cells.
These conditions are markers of genomic instability and help us understand how mutations build up and impact aging. Researching these conditions offers insights into how aging affects cell health and the body's balance. Studying them, along with other biomarkers like epigenetic clocks, can improve our understanding of aging and help develop personalized healthcare strategies to detect and manage age-related diseases early.
"A Pilot Study of UM171-Expanded Cord Blood Grafts for Tandem Auto/Allogeneic Hematopoietic Cell Transplant in High and Ultra-High-Risk Myeloma Patients"
Source
Roy, Jean et al. A Pilot Study of UM171-Expanded Cord Blood Grafts for Tandem Auto/Allogeneic Hematopoietic Cell Transplant in High and Ultra-High-Risk Myeloma Patients. Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy, Volume 0, Issue 0 October 15, 2024.
Overview
This study looked at using a new type of cord blood transplant, called UM171-expanded cord blood, in patients with high-risk multiple myeloma (MM). MM is hard to treat, especially for patients with advanced or high-risk genetic features. Allogeneic (allo) stem cell transplants are the only potential cure, but they have many risks, including disease relapse and complications like graft-versus-host disease (GVHD). Cord blood transplants have shown lower relapse rates and chronic GVHD, but they also have issues like infections and high mortality rates.
The study aimed to see if using UM171-expanded cord blood in a transplant for high-risk MM patients would be safe and effective. This new method improves outcomes in other blood cancers, so researchers wanted to see if it worked for MM.
Researchers enrolled 20 patients with high-risk MM who didn’t have a sibling donor. After an initial treatment, patients received a cord blood transplant with UM171-expanded cells. Researchers monitored safety, how well the transplant worked, and complications like GVHD. They also measured the amount of cancer left (measurable residual disease or MRD) and the patients' quality of life (QoL).
19 patients successfully received the transplant, and most recovered their immune cells quickly. GVHD was seen in 68% of patients, but severe cases were rare. After 3 years, nearly half the patients had no disease progression, and about 68% were still alive. The treatment was well-tolerated, with no unexpected side effects, and patients who didn't relapse had a similar quality of life to the general population.
Researchers found that UM171-expanded cord blood transplants are a promising option for high-risk MM patients. Patients with no detectable cancer before the transplant seemed to benefit the most. This approach could provide a safer transplant option with lower risks of complications.
"Bortezomib in cancer therapy: Mechanisms, side effects, and future proteasome inhibitors"
Source
Olusola Sogbein, Pradipta Paul, Meenakshi Umar, Ali Chaari, Vecihi Batuman, Rohit Upadhyay, Bortezomib in cancer therapy: Mechanisms, side effects, and future proteasome inhibitors, Life Sciences, 2024, 123125, ISSN 0024-3205, https://doi.org/10.1016/j.lfs.2024.123125. October 15, 2024.
Overview
The ubiquitin-proteasome pathway (UPP) controls how proteins break down and helps cells function properly. When this pathway malfunctions, it can lead to cancer. Proteasome inhibitors are drugs that block this process and are especially helpful in treating cancers like multiple myeloma and mantle cell lymphoma.
Bortezomib was the first proteasome inhibitor approved by the FDA for treating multiple myeloma. It works by stopping cancer cells from using the 26S proteasome, which affects several important cellular processes, such as blocking the breakdown of the p53 protein, increasing cell death (apoptosis), and reducing the growth of new blood vessels (angiogenesis). However, Bortezomib can cause serious side effects like nerve damage (peripheral neuropathy), blood vessel problems (thrombotic microangiopathy), and kidney issues (acute interstitial nephritis). These side effects limit how long the drug can be used.
Researchers are working on new proteasome inhibitors to improve treatment and reduce side effects. Carfilzomib, a second-generation drug, is effective for relapsed and refractory multiple myeloma (RRMM) and has a better safety profile. Other next-generation drugs, like Ixazomib, Oprozomib, and Marizomib, are also being tested. Ixazomib works well when combined with other drugs, while Oprozomib and Marizomib show promise in early clinical trials for patients with hard-to-treat multiple myeloma.
These newer drugs have different side effects depending on how they're given, their dosage, and their chemical makeup.
"Immune effector cell-associated enterocolitis following chimeric antigen receptor T-cell therapy in multiple myeloma"
Source
Fortuna, G.G., Banerjee, R., Savid-Frontera, C. et al. Immune effector cell-associated enterocolitis following chimeric antigen receptor T-cell therapy in multiple myeloma. Blood Cancer J. 14, 180 (2024). https://doi.org/10.1038/s41408-024-01167-8 October 16, 2024
Overview
This study reports 14 cases of immune effector cell (IEC)-associated enterocolitis after CAR-T cell therapy in multiple myeloma patients. The condition occurred in 1.2% of patients overall, with higher rates for those receiving ciltacabtagene autoleucel (2.2%) compared to idecabtagene vicleucel (0.2%). Patients experienced severe diarrhea, usually not bloody, around 92.5 days after CAR-T therapy. Gut biopsies showed signs of inflammation, and CAR T-cells were found in the gut in one case. Most patients (71%) were treated with corticosteroids, with 40% seeing improvement. For those who didn't respond to steroids, additional treatments with infliximab or vedolizumab helped some patients. Unfortunately, five patients (36%) died from complications like bowel perforation or infection. The study suggests that early treatment with infliximab or vedolizumab may help reduce the need for high-dose steroids and improve outcomes in managing this rare but serious side effect of CAR-T therapy.
"Impact of age on treatment utilization for newly diagnosed multiple myeloma: a nationwide retrospective cohort study"
Source
Mohyuddin, G.R., Mian, H., Gayowsky, A. et al. Impact of age on treatment utilization for newly diagnosed multiple myeloma: a nationwide retrospective cohort study. Blood Cancer J. 14, 181 (2024). https://doi.org/10.1038/s41408-024-01164-x October 16, 2024.
Overview
This study looked at how age affects treatment decisions for multiple myeloma (MM) patients, specifically the use of autologous stem cell transplants (ASCT) in Ontario, Canada. Researchers wanted to see if "left-digit bias," a tendency to make decisions based on the first digit of a number (like thinking 69 is much younger than 70), influenced these decisions. However, they did not find clear evidence of this bias.
The study analyzed data from 2007 to 2022, focusing on MM patients aged 65 to 75. Even though there is no official age cutoff for ASCT, they found that fewer patients received transplants as they got older, especially between ages 69 and 71. This decline happened even when taking other health factors into account, showing that chronological age still plays a big role in decision-making.
The researchers emphasize that decisions about treatments like ASCT should be based on a patient's overall health and preferences, not just their age. They suggest future studies should explore other treatments and look at how doctors and patients make these decisions.
"Comparative analysis of single versus tandem autologous stem cell transplantation in patients with multiple myeloma in Korea: the KMM2102 study"
Source
Jung, J., Jung, SH., Lee, JJ. et al. Comparative analysis of single versus tandem autologous stem cell transplantation in patients with multiple myeloma in Korea: the KMM2102 study. Sci Rep 14, 24325 (2024). https://doi.org/10.1038/s41598-024-74625-9 October 17, 2024.
Overview
Tandem autologous stem cell transplantation (ASCT) may improve outcomes for patients with multiple myeloma, especially those with advanced disease. In this study, 655 patients were evaluated, with 117 undergoing tandem transplantation (two transplants) and the rest receiving just one. After the first transplant, 24.8% of the tandem group achieved complete remission (CR), which increased to 46.2% after the second transplant.
Patients with advanced multiple myeloma (ISS stage III) or high-risk genetic factors had significantly longer progression-free survival (PFS) after tandem transplantation compared to those who had just one transplant (23.1 vs. 14.7 months for ISS III; 21.7 vs. 13.2 months for high-risk cytogenetics). Tandem transplants were also more effective for patients who didn't reach CR after a single transplant. After adjusting for maintenance therapy, tandem transplantation continued to show benefits in these high-risk patients.
In conclusion, tandem transplantation should be considered for high-risk multiple myeloma patients, as it significantly improves PFS.
"An unbiased lncRNA dropout CRISPR-Cas9 screen reveals RP11-350G8.5 as a novel therapeutic target for multiple myeloma"
Source
Katia Grillone, Serena Ascrizzi, Paolo Cremaschi, Jussara Amato, Nicoletta Polerà, Ottavio Croci, Roberta Rocca, Caterina Riillo, Francesco Conforti, Raffaele Graziano, Diego Brancaccio, Daniele Caracciolo, Stefano Alcaro, Bruno Pagano, Antonio Randazzo, Pierosandro Tagliaferri, Francesco Iorio, Pierfrancesco Tassone; An unbiased lncRNA dropout CRISPR-Cas9 screen reveals RP11-350G8.5 as a novel therapeutic target for multiple myeloma. Blood 2024; 144 (16): 1705–1721. doi: https://doi.org/10.1182/blood.2023021991 October 17, 2024.
Overview
Multiple myeloma (MM) is a cancer that's hard to cure, partly because of changes in both coding and noncoding genes that drive tumor growth and make the cancer resistant to drugs. While long noncoding RNAs (lncRNAs) are known to play an important role in MM, their full potential as therapeutic targets hasn't been explored much.
In this study, researchers conducted a CRISPR-Cas9 screen to investigate 671 lncRNAs in MM cells, including cells resistant to the drug bortezomib (BZB). They used a special data analysis method to find the most important lncRNAs that affect MM survival and are linked to poor patient outcomes. They identified eight key lncRNAs, with one called RP11-350G8.5 standing out as the top target, regardless of BZB resistance.
The study showed that blocking RP11-350G8.5 reduced tumor growth both in the lab and in animal models. This lncRNA was also found to influence the unfolded protein response and trigger immune cell death. Researchers further studied its structure and function, identifying specific regions that could be targeted for new therapies.
The findings suggest that RP11-350G8.5 is a promising therapeutic target for MM, including in patients who don't respond to BZB. This research could lead to the development of new treatments focused on lncRNAs.
"Smoldering Multiple Myeloma: Integrating Biology and Risk into Management, Seminars in Hematology"
Source
Roshani Patel, Elizabeth Hill, Madhav Dhodapkar, Smoldering Multiple Myeloma: Integrating Biology and Risk into Management, Seminars in Hematology, 2024, ISSN 0037-1963, https://doi.org/10.1053/j.seminhematol.2024.10.002. October 18, 2024.
Overview
Smoldering multiple myeloma (SMM) is a condition first identified over 40 years ago, but there’s still much to learn about it, including which patients will progress to symptomatic multiple myeloma (MM). Research shows that both genetic factors and the immune system around the abnormal cells contribute to disease progression. However, current clinical risk models mostly focus on the amount of disease present, not the biology behind it.
Accurately diagnosing SMM is crucial to avoid overtreatment or undertreatment. Ongoing research is exploring whether early treatment might benefit certain high-risk patients. This article reviews the history and biology of SMM, evaluates the usefulness of current risk models, and looks at recent efforts that question standard treatment approaches.
"Results from Arm A of Phase 1/2 DREAMM-6 trial: belantamab mafodotin with lenalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma"
Source
Popat, R., Augustson, B., Gironella, M. et al. Results from Arm A of Phase 1/2 DREAMM-6 trial: belantamab mafodotin with lenalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma. Blood Cancer J. 14, 184 (2024). https://doi.org/10.1038/s41408-024-01155-y October 21, 2024
Overview
Belantamab mafodotin is a new treatment for multiple myeloma (MM). This therapy combines a monoclonal antibody that targets B-cell maturation antigen (BCMA) with a drug that disrupts cell growth. Research has shown that belantamab mafodotin works well with other standard treatments for MM, like bortezomib and lenalidomide, to enhance anti-cancer effects.
Several clinical trials are underway to test how well belantamab mafodotin works in combination with these therapies. The Phase 3 DREAMM-7 trial showed that patients with relapsed or refractory MM (those whose cancer came back or didn’t respond to previous treatments) had a longer time without cancer progression when they received belantamab mafodotin along with bortezomib and dexamethasone, compared to another treatment that included daratumumab.
This study reports results from Arm A of the Phase 1/2 DREAMM-6 trial, which evaluated belantamab mafodotin in combination with lenalidomide and dexamethasone for patients with relapsed or refractory MM who had received at least one prior treatment. The study looked at various doses and how well the treatments worked, tracking side effects and response rates.
A total of 45 patients were included, with most being men and around 68 years old on average. The study found that:
- Safety: No dose-limiting toxicities were reported, meaning patients could tolerate the treatment well. Common side effects included eye problems, low blood cell counts, and infections, but these were generally manageable. Ocular events were seen in 80% of patients, with many having keratopathy (a type of eye damage).
- Efficacy: The overall response rate (ORR), which measures how many patients showed improvement, was 67%. The complete response rate (CRR), where patients had no detectable cancer, was 29%. The median progression-free survival (PFS), or the time until the disease worsens, was 18.4 months.
Belantamab mafodotin combined with lenalidomide and dexamethasone showed promising results in treating MM, with a safety profile similar to previous studies. While more research is needed to determine the best dosing strategies and further assess its effectiveness, early results suggest that this combination treatment could be beneficial for patients with relapsed or refractory MM, particularly those who have been previously treated with lenalidomide.
"Body mass index and risk of over 100 cancer forms and subtypes in 4.1 million individuals in Sweden: the Obesity and Disease Development Sweden (ODDS) pooled cohort study,"
Source
Ming Sun, Marisa da Silva, Tone Bjørge, Josef Fritz, Innocent B. Mboya, Mats Jerkeman, Pär Stattin, Jens Wahlström, Karl Michaëlsson, Bethany van Guelpen, Patrik K.E. Magnusson, Sven Sandin, Weiyao Yin, Ylva Trolle Lagerros, Weimin Ye, Bright Nwaru, Hannu Kankaanranta, Lena Lönnberg, Abbas Chabok, Karolin Isaksson, Nancy L. Pedersen, Sölve Elmståhl, Lars Lind, Linnea Hedman, Christel Häggström, Tanja Stocks, Body mass index and risk of over 100 cancer forms and subtypes in 4.1 million individuals in Sweden: the Obesity and Disease Development Sweden (ODDS) pooled cohort study, The Lancet Regional Health - Europe, Volume 45,2024, 101034, ISSN 2666-7762, https://doi.org/10.1016/j.lanepe.2024.101034. October 2024.
Overview
Obesity, often measured by body mass index (BMI), is known to increase the risk of several cancers. This study aimed to explore whether other cancers might also be linked to obesity and to compare their risk with already established obesity-related cancers.
Researchers analyzed data from over 4 million people in Sweden, tracking their health over many years. They looked for connections between BMI and the risk of developing 122 different types of cancers. They specifically focused on cancers associated with high BMI (≥30 kg/m²) compared to those with normal weight (BMI 18.5–24.9 kg/m²) or those with a higher BMI by 5 kg/m².
After monitoring participants for a total of 100.2 million years, they found:
- Newly Identified Cancers: The study identified 15 cancers in men and 16 in women that could potentially be related to obesity. These included cancers affecting the head and neck, gastrointestinal tract, skin (malignant melanoma), genital organs, endocrine organs, connective tissue, and blood-related cancers.
- Risk Assessment: The analysis revealed that for every 5 kg/m² increase in BMI, the risk of developing these potential obesity-related cancers increased by 17% in men and 13% in women. For established obesity-related cancers, the risk increase was 24% in men and 12% in women.
The findings suggest that many more cancers may be linked to obesity than previously thought, with risk levels similar to those of established obesity-related cancers. The study also highlighted that specific cancer subtypes could be more strongly associated with changes in BMI. However, further research is needed to confirm these associations and account for other factors that might influence cancer risk.
This study underscores the importance of maintaining a healthy weight to potentially reduce the risk of various cancers and highlights the need for more focused research in this area.
"A Systematic Review on the Epidemiology and Treatment Options of Multiple Myeloma in Asia"
Source
Wee-Joo Chng, Chandramouli Nagarajan, Shang-Yi Huang, Pankaj Malhotra, Yu-Yan Hwang, Vivian Blunk, Manmohan Singh, Lin Wang, A Systematic Review on the Epidemiology and Treatment Options of Multiple Myeloma in Asia, Heliyon, 2024, e39698, ISSN 2405-8440, https://doi.org/10.1016/j.heliyon.2024.e39698. October 22, 2024.
Overview
Multiple myeloma (MM) makes up about 15% of all cancer cases worldwide. This systematic review looks at how MM is treated and managed in select Asian countries, aiming to identify important areas for improvement.
Researchers reviewed studies published from 2005 to 2022, focusing on data from countries like China, India, Taiwan, Hong Kong, and Singapore. They followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included 98 studies that analyzed both newly diagnosed MM and relapsed/refractory MM cases. The review examined trends in treatment approaches, including the use of autologous stem cell transplants and advanced therapies like CAR T-cell therapy.
The following are key findings of this study:
- Quality of Evidence: Most studies showed poor quality overall, indicating a need for more robust research in the region.
- Changing Treatments: There is a shift in treatment strategies from using two drugs (doublets) to three drugs (triplets), which may improve patient outcomes.
- Patient Demographics: The majority of participants were adult men aged between 39 to 75 years, with many studies focusing on newly diagnosed cases.
- Epidemiological Data: Limited information was available regarding the incidence and mortality rates of MM in the studied regions, but incidence rates ranged from 1.03 to 1.83 per 100,000 people.
To enhance the management of MM in Asia, several key recommendations were made:
- Develop Affordable Therapies: Collaboration between governments and industry can help provide innovative treatments that improve patient survival and quality of life.
- Encourage Collaborative Research: Forming partnerships among hospitals and research institutions can enhance data quality and resource sharing.
- Increase Patient Education: Raising awareness among healthcare professionals and the public can lead to earlier diagnoses and better treatment adherence.
- Conduct Epidemiological Studies: More research is needed on MM's incidence and risk factors to inform treatment strategies.
- Create National Myeloma Registries: Establishing registries can help track patient outcomes and identify treatment gaps.
- Promote Clinical Trial Participation: Encouraging more patients to join clinical trials can improve treatment recommendations across diverse populations.
- Integrate Palliative Care: Establishing palliative care units can significantly enhance the quality of life for patients, especially those with advanced disease.
While there have been advancements in the treatment of MM, significant challenges remain in Asia. The review highlights the urgent need for improved research, policies, and resources to better address the unique challenges faced by MM patients in the region. By implementing these recommendations, stakeholders can work together to enhance patient outcomes and care for those affected by this cancer.
"Comparison of progression risk of monoclonal gammopathy of undetermined significance by method of detection"
Source
Alissa Visram, Dirk Larson, Aaron D Norman, Angela Dispenzieri, David L Murray, Robert A Kyle, S. Vincent Rajkumar, Susan L. Slager, Shaji K Kumar, Celine M. Vachon; Comparison of progression risk of monoclonal gammopathy of undetermined significance by method of detection. Blood 2024; blood.2024025415. doi: https://doi.org/10.1182/blood.2024025415 October 22, 2024
Overview
Monoclonal gammopathy of undetermined significance (MGUS) is a condition that doesn't show symptoms but can develop into more serious diseases. Usually, MGUS is discovered by chance during other medical tests, as routine screening isn’t recommended. This study looked at whether finding MGUS through screening versus routine clinical exams affects a person’s risk of disease progression.
Researchers reviewed records from 379 screened MGUS cases and 1,384 cases found through clinical exams. They tracked patients for 26.6 years (screened) and 40.1 years (clinical). The 25-year risk of MGUS progressing to a more serious condition was almost the same in both groups: 11.1% for screened and 10.1% for clinically detected cases. Age, sex, and baseline risk scores did not change these results.
For every 100 years of patient follow-up, about 1 in 100 patients experienced disease progression, regardless of how MGUS was detected. The method of detection also didn’t change how other risk factors affected progression. Researchers concluded that the risk of MGUS progression is similar whether it’s detected by screening or incidentally and suggested more studies to see if tailored follow-up care for screened MGUS patients can improve outcomes.
A recent study aimed to find the best treatment for patients with multiple myeloma who have not responded to lenalidomide (LEN) and are experiencing their first relapse. Researchers tested a combination of three medications: ixazomib (IXA), pomalidomide (POM), and dexamethasone (DEX). They compared this triplet therapy to a double therapy of POM and DEX alone.
Results showed that the triplet therapy was more effective, with a 63.2% overall response rate (ORR) compared to 43.6% for the double therapy. Patients receiving the triplet also had a significantly better progression-free survival (PFS), lasting an average of 20.3 months, while those on the double therapy averaged 7.5 months.
While more patients on the triplet therapy experienced blood-related side effects, other adverse events were similar between the two groups. The findings suggest that this all-oral triplet therapy should be tested further in larger studies for patients who haven't responded to LEN.
For more information, this trial is registered at www.clinicaltrials.gov (#NCT02004275).
"Siltuximab for Chimeric Antigen Receptor T-Cell Therapy Related CRS and ICANS - A Multicenter Retrospective Analysis"
Source
Amneet Bajwa, Qiuhong Zhao, Marcus J Geer, Chenyu Lin, James Westholder, Joeseph Maakaron, Monalisa Ghosh, David G Frame, Ahmed Galal, Justin Tossey, Nausheen Ahmed, Evandro D Bezerra, Nathan Denlinger, Marcos J de Lima, Narendranath Epperla, Paolo F. Caimi, Timothy J Voorhees; Siltuximab for Chimeric Antigen Receptor T-Cell Therapy Related CRS and ICANS - A Multicenter Retrospective Analysis. Blood Adv 2024; bloodadvances.2024013688. doi: https://doi.org/10.1182/bloodadvances.2024013688 October 22, 2024.
Overview
CAR T-cell therapies have shown great success in treating blood cancers, but they can cause serious side effects like cytokine release syndrome (CRS) and neurotoxicity (ICANS), which can be hard to treat when they don’t respond to initial therapies. Siltuximab, a medication that blocks IL-6 (a protein involved in immune response), may help manage these effects.
In a study across six medical centers, researchers reviewed the effects of siltuximab on 54 patients who had CRS or ICANS after CAR T-cell therapy. Among patients with CRS who had already received other treatments, 75% showed improvement with siltuximab. For patients with ICANS who had been previously treated with steroids, 60% improved.
This study, the largest so far on siltuximab for CRS and ICANS, suggests that siltuximab could be effective in reducing these side effects, even when prior treatments haven’t worked. The findings support further research to confirm siltuximab’s potential benefits.
"Real-World Outcomes of Upfront Autologous Hematopoietic Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma with Deletion 17p, Transplantation and Cellular Therapy"
Source
Curtis Marcoux, Oren Pasvolsky, Denái R. Milton, Mark R. Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Hans C. Lee, Krina K. Patel, Partow Kebriaei, Amna Ahmed, Yosra Aljawai, Sheeba K. Thomas, Robert Z. Orlowski, Elizabeth J. Shpall, Richard E. Champlin, Muzaffar H. Qazilbash, Real-World Outcomes of Upfront Autologous Hematopoietic Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma with Deletion 17p, Transplantation and Cellular Therapy, 2024, ISSN 2666-6367, https://doi.org/10.1016/j.jtct.2024.10.011. October 22, 2024.
Overview
Multiple myeloma (MM) outcomes vary widely, and certain genetic factors can predict a poor prognosis. One key factor is deletion of the short arm of chromosome 17, known as del(17p). This study focused on real-world outcomes for newly diagnosed MM patients with del(17p) who received an early autologous stem cell transplant (auto-HCT) at MD Anderson Cancer Center.
Researchers reviewed data from 115 patients treated between 2008 and 2018. Most patients were male, with a median age of 62. After transplant, 42% achieved a complete response (CR), and 55% had no detectable disease (MRD-negative). Median progression-free survival (PFS) was about 20 months, while overall survival (OS) was roughly 72 months, with a 5-year survival rate of 53%.
Patients with both del(17p) and a t(4;14) abnormality had worse outcomes, with median PFS and OS of 11.5 and 22.4 months, respectively. In addition, female sex was linked to shorter PFS and OS, while achieving MRD-negative status and using maintenance therapy were associated with better outcomes.
The study underscores del(17p) as a high-risk marker in MM and suggests that patients with del(17p) plus t(4;14) may benefit from new, more effective treatments.
"Disparities in electronic health record patient portal activation and use among people with hematological malignancies"
Source
Angela M. Trammel, Bryan A. Sisk, Mark A. Fiala, Disparities in electronic health record patient portal activation and use among people with hematological malignancies, Journal of Geriatric Oncology,2024, 102135, ISSN 1879-4068, https://doi.org/10.1016/j.jgo.2024.102135. October 23, 2024.
Overview
Electronic health record (EHR) portals help patients access health information, communicate with providers, and manage appointments, which can improve patient engagement and treatment adherence. However, not all patients use these portals equally. This study looked at how people with blood cancers, like leukemia, myeloma, and lymphoma, use EHR portals, as their treatment often involves frequent appointments and complex care.
The study examined 2023 patient data from Washington University School of Medicine, which serves a diverse population, including many underserved groups. Of the patients included, 86% activated their portal, and of these, 84% logged in after a visit. However, age, race, and socioeconomic status (SES) influenced who activated and used the portal. African American and lower-SES patients were less likely to log in after a visit, indicating disparities in EHR usage.
Barriers to using these portals could include technology access, usability, and cultural attitudes, with some patients feeling uneasy about digital health systems or suspecting that portals are more about payment than care. Additionally, costs associated with portal-based provider messaging may deter engagement, which could further impact health equity.
The study’s findings suggest that healthcare reliance on portals may unintentionally worsen disparities, as certain groups miss out on critical information and care management tools. Expanding EHR research and reducing barriers could improve health outcomes across diverse patient populations.
"First Line Treatment of Newly Diagnosed Transplant Eligible Multiple Myeloma Recommendations from a Canadian Consensus Guideline Consortium, Clinical Lymphoma Myeloma and Leukemia"
Source
Sahar Khan, Debra J. Bergstrom, Julie Côté, Rami Kotb, Richard LeBlanc, Martha L. Louzada, Hira S. Mian, Ibraheem Othman, Gabriele Colasurdo, Alissa Visram, First Line Treatment of Newly Diagnosed Transplant Eligible Multiple Myeloma Recommendations from a Canadian Consensus Guideline Consortium, Clinical Lymphoma Myeloma and Leukemia, 2024, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2024.10.012. October 23, 2024.
Overview
With new, effective therapies available for multiple myeloma (MM), the role of autologous stem cell transplantation (ASCT) as a first-line treatment is under review, especially for standard-risk patients. However, for high-risk patients, outcomes remain less favorable, even with newer treatments. Today, the leading approach for transplant-eligible MM (TEMM) combines a quadruplet induction therapy—using an anti-CD38 monoclonal antibody with a proteasome inhibitor and immunomodulatory drug—followed by ASCT and maintenance therapy. This method aims for deep, long-lasting responses.
To guide physicians and patients, the Canadian Consensus Guideline Consortium (CGC) has developed recommendations for initial TEMM treatment. These guidelines cover eligibility for ASCT, treatment stages (induction, mobilization, collection, conditioning, consolidation, and maintenance), care for high-risk patients, side effect management, response evaluation, and monitoring for relapse. The CGC will review and update these recommendations periodically to reflect advancements in MM care.
"Soluble B-cell maturation antigen levels for disease monitoring in oligosecretory and nonsecretory relapsed multiple myeloma"
Source
Daisuke Ikeda, Shuichi Aikawa, Chiho Misono, Mitsuaki Oura, Fuminari Fujii, Hajime Sakuma, Masanori Toho, Atsushi Uehara, Rikako Tabata, Kentaro Narita, Masami Takeuchi, Tomohisa Watari, Yoshihito Otsuka, Kosei Matsue; Soluble B-cell maturation antigen levels for disease monitoring in oligosecretory and nonsecretory relapsed multiple myeloma. Blood 2024; blood.2024026028. doi: https://doi.org/10.1182/blood.2024026028 October 23, 2024.
Overview
Soluble B-cell maturation antigen (sBCMA) is a marker found at high levels on multiple myeloma (MM) cells. This study explored if sBCMA levels reflect myeloma tumor size and whether it could help monitor patients with oligo-secretory or non-secretory (O-S/Non-S) MM, where traditional markers are less reliable.
In 115 newly diagnosed MM patients, sBCMA levels were compared with other tumor indicators: M-protein levels, bone marrow plasma cells (BMPCs), circulating tumor cells (CTCs), and tumor volume as shown by whole-body MRI. Higher sBCMA levels were linked with advanced disease stage, chromosome 1q21 abnormalities, and higher CTC counts. Strong correlations were found between sBCMA and BMPC percentage, moderate ones with total tumor volume, and paraprotein levels in specific MM subtypes.
In both O-S/Non-S and other MM cases, sBCMA changes matched disease progression. Notably, in O-S/Non-S patients, sBCMA levels often rose six months before relapse, suggesting it could be an early warning sign. These findings indicate that sBCMA is useful for tracking treatment response and predicting relapse in MM, especially in patients with harder-to-monitor disease types.
"Enitociclib, a selective CDK9 inhibitor: in vitro and in vivo preclinical studies in multiple myeloma"
Source
Son Tran, Patrick Sipila, Melanie M. Frigault, Beatrix Stelte-Ludwig, Amy J. Johnson, Joseph Birkett, Raquel Izumi, Ahmed Hamdy, Ranjan Maity, Nizar J. Bahlis, Paola Neri, Aru Narendran; Enitociclib, a selective CDK9 inhibitor: in vitro and in vivo preclinical studies in multiple myeloma. Blood Neoplasia 2024; 100050. doi: https://doi.org/10.1016/j.bneo.2024.100050 October 24, 2024.
Overview
This study screened 216 small-molecule inhibitors to find options that specifically block multiple myeloma (MM) cell growth. Enitociclib, a CDK9 inhibitor, showed strong effects in reducing MM cell survival and triggering cell death in four MM cell lines. It worked by stopping certain signals (phosphorylation of RNA Pol II) that MM cells need for survival and by lowering levels of key cancer-related proteins, like c-Myc and Mcl-1. Enitociclib also worked well with other MM drugs, such as bortezomib and lenalidomide. These findings suggest enitociclib could be a valuable new treatment for MM, alone or combined with other MM therapies.
"Low platelet counts and low CD4/CD8 ratios at apheresis increase the risk of CAR-T cell manufacturing failure in myeloma"
Source
Tomoyasu Jo, Kyoko Yoshihara, Masaki Ri, Nobuhiro Tsukada, Naoya Mimura, Keiko Fujii, Kentaro Fukushima, Shin-ichiro Fujiwara, Yuji Shimura, Kyoko Haraguchi, Koji Kato, Atsushi Satake, Akiyo Yoshida, Rikio Suzuki, Junko Ikemoto, Keita Iwaki, Wataru Takeda, Noboru Yonetani, Ryuji Tanosaki, Minami Yamada-Fujiwara, Kaoru Kahata, Tokiko Nagamura-Inoue, Satoshi Yoshihara, Yasuyuki Arai; Low platelet counts and low CD4/CD8 ratios at apheresis increase the risk of CAR-T cell manufacturing failure in myeloma. Blood Neoplasia 2024; 100051. doi: https://doi.org/10.1016/j.bneo.2024.100051 October 24, 2024.
Overview
CAR T-cell therapy is an important treatment for relapsed or refractory multiple myeloma, but manufacturing issues can prevent some patients from receiving it. In a study from Japan, researchers looked at 154 myeloma patients who underwent apheresis for the CAR T-cell therapy idecabtagene vicleucel. Manufacturing failed in 13 patients (8.4%). Those with manufacturing failure often had specific risk factors, such as deletion 17p at diagnosis, recent use of alkylating agents (within 6 months), and more previous rounds of chemotherapy. Patients in the failed group also had lower hemoglobin, platelet counts, and CD4/CD8 ratios. Multivariate analysis showed that low platelet counts and low CD4/CD8 ratios significantly increased the risk of manufacturing failure. Alkylating agents were linked to reduced platelet counts and CD4/CD8 ratios. To improve CAR T-cell therapy outcomes, avoiding these risk factors and using tailored strategies could help myeloma patients succeed with this treatment.
"Modernizing Multiple Myeloma Clinical Trial Eligibility to Improve Equity and Inclusivity by Hematological Parameter"
Source
Lauren Merz, Monique Hartley-Brown, Maureen Achebe, Craig Cole, Bindu Kanapuru, Ola Banjo, George Mulligan, Katie Wozniak, Anne Quinn Young, Hearn Jay Cho, Modernizing Multiple Myeloma Clinical Trial Eligibility to Improve Equity and Inclusivity by Hematological Parameters, Seminars in Hematology,2024, ISSN 0037-1963, https://doi.org/10.1053/j.seminhematol.2024.10.008. October 25, 2024.
Overview
CAR T-cell therapy is an important treatment for relapsed or refractory multiple myeloma, but manufacturing issues can prevent some patients from receiving it. In a study from Japan, researchers looked at 154 myeloma patients who underwent apheresis for the CAR T-cell therapy idecabtagene vicleucel. Manufacturing failed in 13 patients (8.4%). Those with manufacturing failure often had specific risk factors, such as deletion 17p at diagnosis, recent use of alkylating agents (within 6 months), and more previous rounds of chemotherapy. Patients in the failed group also had lower hemoglobin, platelet counts, and CD4/CD8 ratios. Multivariate analysis showed that low platelet counts and low CD4/CD8 ratios significantly increased the risk of manufacturing failure. Alkylating agents were linked to reduced platelet counts and CD4/CD8 ratios. To improve CAR T-cell therapy outcomes, avoiding these risk factors and using tailored strategies could help myeloma patients succeed with this treatment.
"In vitro testing of drug response in primary multiple myeloma cells using a microwell-based technology"
Source
Josefine Krüger, Igor Wolfgang Blau, Olga Blau, Alice Bettelli, Laura Rocchi, Massimo Bocchi, Jan Krönke, Lars Bullinger, Ulrich Keller, Axel Nogai, In vitro testing of drug response in primary multiple myeloma cells using a microwell-based technology, Leukemia Research, 2024, 107599, ISSN 0145-2126, https://doi.org/10.1016/j.leukres.2024.107599. October 26, 2024.
Overview
Despite many drugs available to treat multiple myeoma, predicting which ones will work best for each patient remains difficult. This study tested a new technology called the Cellply CC-Array®, which uses small microwells and fluorescent markers to measure how myeloma cells respond to drugs in the lab. Researchers collected bone marrow cells from 22 patients and tested how their myeloma cells reacted to drugs like melphalan, bortezomib, and dexamethasone. The responses in the lab matched how patients responded to these drugs in real life. However, it was harder to measure reactions to drugs like lenalidomide, daratumumab, and elotuzumab because myeloma cells didn’t survive long enough in the lab. This technology also helped evaluate how immune cells, like NK and T cells, could attack myeloma cells. While these early results are promising, more testing with larger patient groups is needed to confirm its effectiveness.
"Divergence of variant antibodies following SARS-CoV-2 booster vaccines in myeloma and impact of hybrid immunity"
Source
Moreno, A., Manning, K., Azeem, M.I. et al. Divergence of variant antibodies following SARS-CoV-2 booster vaccines in myeloma and impact of hybrid immunity. npj Vaccines 9, 201 (2024). https://doi.org/10.1038/s41541-024-00999-6 October 27, 2024.
Overview
People with blood cancers, like multiple myeloma, face higher risks of complications from COVID-19. Vaccines, including primary series and monovalent boosters, have been shown to reduce severe illness, hospital stays, and deaths in these patients. This study looked at antibody responses in multiple myeloma patients after receiving either a monovalent (WA1) or bivalent (WA1/BA.5) COVID-19 booster. The bivalent booster improved the range of antibodies that could bind to the virus, but it didn’t significantly boost the ability to neutralize current COVID-19 variants. Researchers also noted that factors like hybrid immunity and immune imprinting influence how well these vaccines work.
"Multiple myeloma: What is the most cost-effective imaging strategy for initial detection of bone lesions?"
Source
Gyftopoulos, S., Hanly, A., Subhas, N. et al. Multiple myeloma: What is the most cost-effective imaging strategy for initial detection of bone lesions?. Skeletal Radiol (2024). https://doi.org/10.1007/s00256-024-04810-4 October 28, 2024.
Overview
This study looked at the cost-effectiveness of different imaging methods to detect bone damage in patients at risk for multiple myeloma. Using a 20-year model, researchers compared five imaging techniques: skeletal survey (SS), low-dose CT (LDCT), PET/CT, and whole-body MRI (WBMRI) with and without diffusion (DIFF). The study estimated costs in 2024 U.S. dollars and used quality-adjusted life years (QALYs) to measure effectiveness, setting a cost-effectiveness threshold of $100,000 per QALY.
The results showed that the most cost-effective imaging method depends on the patient’s risk of progressing from MGUS (a precursor condition) to multiple myeloma. For patients with no risk factors, LDCT was the most cost-effective, offering high benefits at lower costs. For patients with one or two risk factors, WBMRI with diffusion provided the most value. PET/CT and WBMRI without diffusion were not cost-effective in any scenario.
Overall, LDCT and WBMRI with diffusion are recommended as cost-effective options for diagnosing multiple myeloma in at-risk patients, depending on individual risk levels.
"Patient-reported outcomes of chimeric antigen receptor T-cell therapy in hematologic malignancies: a systematic review and meta-analysis"
Source
Park, H.J., Jeong, H., Yim, H.W. et al. Patient-reported outcomes of chimeric antigen receptor T-cell therapy in hematologic malignancies: a systematic review and meta-analysis. Sci Rep 14, 25752 (2024). https://doi.org/10.1038/s41598-024-77210-2 October 28, 2024.
Overview
This study reviewed patient-reported outcomes (PROs) for people with blood cancers who received CAR-T cell therapy. By analyzing data from 15 studies, researchers looked at how CAR-T therapy impacted six areas: overall health, pain, fatigue, depression, social function, and cognitive function. Results showed that CAR-T therapy led to improvements across all these areas, with the most significant boost in general health and smaller yet meaningful gains in cognitive function. The study highlights that both medical expertise and patient preferences should be carefully considered when deciding on CAR-T cell therapy for blood cancers.
"The mediating effect of stigma on the relationship between fear of disease progression and social alienation in patients with haematological malignancies"
Source
Shi, D., Li, R., Chen, P., Zhong, J., Wang, K., Wang, D., & Zhu, H. (2024). The mediating effect of stigma on the relationship between fear of disease progression and social alienation in patients with haematological malignancies. Hematology, 29(1). https://doi.org/10.1080/16078454.2024.2416723 October 28, 2024.
Overview
This study looked at how shame, fear of disease progression, and social isolation are linked in patients with blood cancers, such as leukemia and multiple myeloma. Researchers found that patients with more fear about their disease progressing felt more shame, which led to a higher sense of social isolation. This effect was strongest in patients who felt self-conscious or stigmatized due to their illness, symptoms, or treatment side effects.
The study suggests that healthcare providers should focus on reducing patients' fear and shame to help them feel less isolated. Psychological support, mindfulness exercises, and social activities may be beneficial in improving social connections and mental well-being for patients with blood cancers.
"Advances in adoptive cellular immunotherapy and therapeutic breakthroughs in multiple myeloma"
Source
Pu, J., Liu, T., Sharma, A. et al. Advances in adoptive cellular immunotherapy and therapeutic breakthroughs in multiple myeloma. Exp Hematol Oncol 13, 105 (2024). https://doi.org/10.1186/s40164-024-00576-6 October 28, 2024.
Overview
This study highlights how adoptive cellular immunotherapy (ACT) has transformed treatment options for multiple myeloma (MM). ACT works by using modified versions of a patient’s own immune cells to target and kill cancer cells. These therapies, like CAR-T cell therapy, have progressed significantly from experimental use to more routine applications in MM treatment. New types of ACTs, including CAR-natural killer (CAR-NK) cells and cytokine-induced killer (CIK) cells, are also showing promise for MM patients, especially those who don’t respond to standard therapies.
CAR-T therapy, which often targets BCMA, has been the most successful so far, offering strong, durable responses. However, ACTs can cause side effects, like cytokine release syndrome (CRS) and neurotoxicity, and may not work if cancer cells adapt to escape detection. Researchers are working on ways to improve safety and effectiveness, such as creating “off-the-shelf” CAR-T cells that are pre-made and more readily available.
To enhance ACT outcomes, scientists are combining it with other MM drugs, like immunomodulators and monoclonal antibodies, to boost effectiveness and reduce resistance. Future research is focused on refining ACT designs, expanding cell types for treatment, and developing ways to select the right patients for these therapies. Collaboration across clinical and research fields will be key in advancing these therapies from research to widespread use, providing MM patients with more durable and accessible treatment options.
"Melanoma Antigen Genes (MAGE); novel functional targets in Multiple Myeloma"
Source
Anna Huo-Chang Mei, Alessandro Laganà, Roman Osman, Hearn Jay Cho, Melanoma Antigen Genes (MAGE); novel functional targets in Multiple Myeloma, Seminars in Hematology, 2024, ISSN 0037-1963, https://doi.org/10.1053/j.seminhematol.2024.10.007. October 28, 2024.
Overview
This study explores the role of Melanoma Antigen Genes (MAGE), particularly MAGE-A3 and MAGE-C1, in multiple myeloma (MM). MAGE genes are linked to various cancers, with MAGE-A3 expression rising significantly after relapse in MM, often signaling chemotherapy resistance and poor outcomes.
MAGE proteins help cancer cells survive by impacting cell division and preventing programmed cell death (apoptosis). MAGE-A3 and Kap1 join to form a complex that tags proteins like p53, a tumor suppressor, for degradation. This allows cancer cells to grow and resist chemotherapy. Importantly, blocking MAGE-A3's function in MM cells triggers cell death, making it a potential therapeutic target.
Researchers have identified new strategies to block MAGE-A3. One approach includes small molecules to block protein interactions, while another targets MAGE-A3 for destruction, leaving healthy tissues unaffected. This research highlights MAGE-A3 as a promising drug target for MM and possibly other cancers that express MAGE genes.
"Soluble B-cell maturation antigen levels for disease monitoring in oligo- and non-secretory relapsed multiple myeloma"
Source
Daisuke Ikeda, Shuichi Aikawa, Chiho Misono, Mitsuaki Oura, Fuminari Fujii, Hajime Sakuma, Masanori Toho, Atsushi Uehara, Rikako Tabata, Kentaro Narita, Masami Takeuchi, Tomohisa Watari, Yoshihito Otsuka, Kosei Matsue, Soluble B-cell maturation antigen levels for disease monitoring in oligo- and non-secretory relapsed multiple myeloma, Blood, 2024, ISSN 0006-4971, https://doi.org/10.1182/blood.2024026028. October 28, 2024.
Overview
This study looked at soluble B-cell maturation antigen (sBCMA), a protein found in higher levels on multiple myeloma (MM) cells. Researchers studied sBCMA in 115 newly diagnosed MM patients to see if it was linked to tumor volume and whether it could be a marker for patients with oligo-secretory or non-secretory (O-S/Non-S) MM, who don't produce high levels of typical myeloma markers.
The study found that sBCMA levels were linked with several indicators of tumor burden, like the percentage of cancerous plasma cells in the bone marrow, circulating tumor cells (CTCs), and tumor volume detected through MRI. Higher sBCMA levels were also tied to later stages of MM and certain genetic changes associated with aggressive disease. Changes in sBCMA levels matched disease progression, and it could even detect relapses up to six months before they happened in many O-S/Non-S patients.
These findings suggest that sBCMA could be an effective tool for tracking disease in MM patients, especially those with O-S/Non-S MM, and for predicting early relapse.
"Irradiated Bone Marrow Volume is Associated with Hematologic Toxicity in Patients with Multiple Myeloma"
Source
Samuel C. Zhang, Sungjin Kim, Jennifer Steers, Bradley Stiehl, Katrina D. Silos, Giana Grigsby, Maria Oorloff, Taman Upadhaya, Robert A. Vescio, David R. Oveisi, Behrooz Hakimian, Katelyn M. Atkins, Leslie K. Ballas, Irradiated Bone Marrow Volume is Associated with Hematologic Toxicity in Patients with Multiple Myeloma, International Journal of Radiation Oncology*Biology*Physics, 2024, ISSN 0360-3016, https://doi.org/10.1016/j.ijrobp.2024.10.017. October 28, 2024.
Overview
This study examined the effects of palliative radiotherapy (RT) on blood cell counts in multiple myeloma (MM) patients. In particular, the researchers looked at whether the volume of bone marrow exposed to certain radiation levels, measured in units called "Gray" (Gy), was linked to blood toxicity—a problem that can lead to transfusions, therapy interruptions, or hospital stays.
The study included 125 MM patients who received RT for pain relief. It found that bone marrow receiving 5-15 Gy was significantly associated with an increased risk of blood-related side effects. Patients with later-stage or relapsed MM, who had received multiple prior therapies, were also more likely to experience blood toxicity. This suggests that the more heavily treated the patient, the greater the likelihood of complications.
This information could be useful for RT planning in MM patients, as reducing the volume of bone marrow exposed to high radiation may help minimize blood toxicity. This could be especially important for patients awaiting stem cell transplants or CAR T-cell therapy or those in clinical trials that require stable blood counts.
"Identifying the prognostic significance of mitophagy-associated genes in multiple myeloma: a novel risk model construction"
Source
Min, R., Hu, Z. & Zhou, Y. Identifying the prognostic significance of mitophagy-associated genes in multiple myeloma: a novel risk model construction. Clin Exp Med 24, 249 (2024). https://doi.org/10.1007/s10238-024-01499-6 October 29, 2024.
Overview
To improve outcomes for multiple myeloma (MM) patients, tailored treatment strategies based on precise risk assessment are crucial. However, existing prognostic models for MM have limitations, and the variability in patient prognosis remains a challenge. Recent studies have shown that mitochondrial autophagy (mitophagy) plays an important role in MM development and response to treatment.
This study aims to analyze the prognostic significance of genes related to mitophagy in MM and create a new predictive risk model. Researchers utilized gene expression data from publicly available databases to identify key genes associated with mitophagy in MM patients. They focused on five specific genes—CDC6, PRIM1, SNRPB, TOP2A, and ZNF486—found to be linked to patient outcomes.
The team developed a risk model based on these five genes, which successfully categorized patients into high-risk and low-risk groups. This model demonstrated strong predictive ability for survival rates and was validated with data from multiple sources. Additionally, the research included an assessment of immune response and drug sensitivity, revealing differences in immune cell types and responses to chemotherapy between the risk groups.
Importantly, the study highlights the potential of the identified genes as targets for treatment, offering insights into personalized therapy options for MM patients. Overall, the newly developed prognostic model may enhance how healthcare providers assess risk and tailor treatments for individuals with MM, paving the way for improved patient care and outcomes.
This research lays the groundwork for further exploration of mitophagy-related genes in MM, which could lead to innovative treatment strategies and a better understanding of this challenging disease.
"Association of lipid levels, adipokines and multiple myeloma: a two-sample multivariate Mendelian randomization study"
Source
Ding, Y., Zhang, Y., Zhang, X. et al. Association of lipid levels, adipokines and multiple myeloma: a two-sample multivariate Mendelian randomization study. Sci Rep 14, 25961 (2024). https://doi.org/10.1038/s41598-024-74838-y October 29, 2024.
Overview
Researchers explored the potential links between lipid levels, adipokines (substances secreted by fat tissue), and multiple myeloma (MM), a type of blood cancer. While previous studies suggested a connection, this research aimed to determine whether these factors actually cause MM.
- No Causal Link Found: Using genetic data, the study concluded that there is no significant causal relationship between levels of certain lipids (like cholesterol and triglycerides) or adipokines (like adiponectin, leptin, and resistin) and the risk of developing MM.
- Role of BMI: Body mass index (BMI) was found to have a causal relationship with MM. This means that being overweight may increase the risk of developing the disease, but the levels of lipids and adipokines did not show a similar effect.
- Adipokines and MM:
- Adiponectin: Although lower levels of this adipokine were previously linked to MM, this study did not find a direct causal relationship.
- Leptin: The research highlighted mixed findings about leptin's role in MM, suggesting it may affect how the cancer progresses rather than causing it.
- Resistin: No causal connection between resistin levels and MM was found.
- Lipid Levels: Similar to adipokines, changes in lipid levels were not shown to cause MM, though some studies indicated a correlation with cancer progression.
- Need for Further Research: The authors acknowledged that while their findings do not support a strong causal link between these factors and MM, they cannot completely rule out a weak association. More research is needed to explore the underlying mechanisms.
This study suggests that while obesity (as indicated by BMI) may increase the risk of multiple myeloma, levels of lipids and adipokines do not appear to play a significant causal role. Understanding the complex interactions between these factors is essential for future research on cancer prevention and treatment.
"Challenges in the treatment of soft-tissue plasmacytoma: a retrospective analysis of 120 patients with extramedullary multiple myeloma"
Source
Zolnowski, D., Karp, S., Warncke, P. et al. Challenges in the treatment of soft-tissue plasmacytoma: a retrospective analysis of 120 patients with extramedullary multiple myeloma. J Cancer Res Clin Oncol 150, 482 (2024). https://doi.org/10.1007/s00432-024-05993-y October 29, 2024.
Overview
A recent study investigated the outcomes of patients with multiple myeloma who also have soft-tissue plasmacytoma (STP), a condition characterized by the presence of cancer cells outside of the bone marrow. The researchers reviewed the medical records of 120 patients treated from 2007 to 2022 and found that 67% showed at least a partial response to the first-line treatment, while 59% had positive results on imaging tests. The median progression-free survival (PFS) was 10.5 months, with patients having primary STP living longer (20.2 months) than those with secondary STP (5.8 months). The median overall survival (OS) was 24.5 months, highlighting a significant difference based on the type of STP.
The study identified secondary STP and organ involvement as major negative prognostic factors, indicating that patients with these characteristics had worse PFS and OS. Despite the availability of novel therapies, the results reveal that outcomes for STP patients remain poor compared to those without extramedullary involvement. The findings emphasize the urgent need for improved treatment strategies, including immunotherapies and cell therapies, as well as the establishment of standardized guidelines to enhance patient outcomes in this challenging subset of multiple myeloma.