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 March 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 March 2024)
"A novel T cell-redirecting anti-GPRC5D × CD3 bispecific antibody with potent antitumor activity in multiple myeloma preclinical models"
Source
Tomita, U., Ishimoto, Y., Ri, M. et al. A novel T cell-redirecting anti-GPRC5D × CD3 bispecific antibody with potent antitumor activity in multiple myeloma preclinical models. Sci Rep 14, 5135 (2024). https://doi.org/10.1038/s41598-024-55143-0. March 1, 2024.
Overview
In about 90% of multiple myeloma patients, a protein called GPRC5D is found in the cancerous cells. Researchers have developed a new medicine called BsAb5003, which is a special type of antibody that can target both GPRC5D and another protein called CD3.
In this study, scientists tested how well BsAb5003 works against multiple myeloma. They found that BsAb5003 can kill multiple myeloma cells that have GPRC5D on their surface. It also activates a type of immune cell called T cells and makes them release substances that can help fight cancer.
The researchers looked at samples from 49 multiple myeloma patients and found that GPRC5D was present in many of them, including those who had been treated a lot and those whose cancer was considered high-risk.
In lab tests using cells from multiple myeloma patients, BsAb5003 showed strong effects against the cancer cells, especially when the cells had a lot of GPRC5D. When BsAb5003 was combined with other drugs called immunomodulatory drugs (IMiDs), it worked even better in killing multiple myeloma cells and activating T cells.
In experiments on mice with multiple myeloma, BsAb5003 slowed down the growth of tumors by bringing in T cells to fight the cancer.
These findings suggest that BsAb5003 could be a powerful treatment for many multiple myeloma patients, either on its own or combined with other drugs like IMiDs. This new medicine could offer hope to people with multiple myeloma, including those whose cancer is hard to treat.
"Health care costs among patients with hematologic malignancies receiving allogeneic transplants: a US payer perspective"
Source
Maziarz, R.T., et. al. Health care costs among patients with hematologic malignancies receiving allogeneic transplants: a US payer perspective. Blood Adv (2024) 8 (5): 1200–1208. https://doi.org/10.1182/bloodadvances.2023011033 March 1, 2024.
Overview
This retrospective study examines healthcare costs among patients with hematologic malignancies who receive allogeneic transplants. It considers the following:
- "Because of short-term and long-term care needs, allogeneic transplants are costly.
- Novel therapies that reduce both the length of hospitalization after hematopoietic stem-cell transplantation (HCT) and complication rates may significantly reduce allo-HCT costs."
"Salvage Therapies including Retreatment with BCMA-directed Approaches Following BCMA CAR-T Relapses for Multiple Myeloma"
Source
Reyes, K.R., Liu, Y.,Hunang, C., et al. Salvage Therapies including Retreatment with BCMA-directed Approaches Following BCMA CAR-T Relapses for Multiple Myeloma. Blood Adv bloodadvances.2023012066. https://doi.org/10.1182/bloodadvances.2023012066 March 1, 2024.
Overview
The key points discussed in this study are the following:
- "Retreatment with BCMA-directed therapies after prior BCMA-directed CAR-T can elicit high response rates in multiple myeloma patients.
- Despite high response rates, durability of responses to salvage therapies after BCMA-directed CAR-T relapses are currently sub-optimal."
"CAR T therapies in multiple myeloma: unleashing the future"
Source
Sheykhhasan, M., Ahmadieh-Yazdi, A., Vicidomini, R. et al. CAR T therapies in multiple myeloma: unleashing the future. Cancer Gene Ther (2024). https://doi.org/10.1038/s41417-024-00750-2. March 4, 2024
Overview
From the abstract: "Despite the challenges and obstacles associated with these treatments, the recent approval of the second FDA multiple myeloma CAR T-cell therapy has sparked immense promise in the field. Thus far, the results indicate its potential as a highly effective therapeutic solution. Moreover, ongoing preclinical and clinical trials are exploring the capabilities of CAR T-cells in targeting specific antigens on myeloma cells, offering hope for patients with relapsed/refractory multiple myeloma (RRMM). These advancements have shown the potential for CAR T cell-based medicines or combination therapies to elicit greater treatment responses and minimize side effects. In this context, it is crucial to delve into the history and functions of CAR T-cells while acknowledging their limitations. We can strategize and develop innovative approaches to overcome these barriers by understanding their challenges. This article aims to provide insights into the application of CAR T-cells in treating multiple myeloma, shedding light on their potential, limitations, and strategies employed to enhance their efficacy."
"Round Table Discussion on Optimal Clinical Trial Design in Precursor Multiple Myeloma"
Source
Ghobrial, I.M., Gormley, N., Mateos, M.V., et.al. Round Table Discussion on Optimal Clinical Trial Design in Precursor Multiple Myeloma. Blood Cancer Discov OF1–OF7. https://doi.org/10.1158/2643-3230.BCD-24-0022. March 4, 2024.
Overview
In the past, doctors often just watched and waited for early blood conditions to develop into more serious problems. But new treatments might change that. These treatments aim to be safe and help people live longer or keep symptoms away longer. The goal is to find therapies that make survival better and stop symptoms from happening, all while being safe.
When testing these new treatments in trials, doctors need to consider the following: They have to pick the right people who are at risk, make sure the treatments are safe, choose the right amount of medicine, and decide what to look for to see if the treatment is working. They also need to compare the new treatment to what's already available and think about how it affects people's quality of life. Doing all this can help them figure out if the benefits of the treatment outweigh the risks.
"Socioeconomic Status and Overall Survival Among Patients With Hematological Malignant Neoplasms"
Source
Nielsen LH, Kristensen DT, Jakobsen LH, et al. Socioeconomic Status and Overall Survival Among Patients With Hematological Malignant Neoplasms. JAMA Netw Open. 2024;7(3):e241112. doi:10.1001/jamanetworkopen.2024.1112 March 4, 2024.
Overview
From the study: "This cohort study including 5677 patients with hematological malignant neoplasms in Denmark found no significant differences in survival according to socioeconomic status within patients with multiple myeloma, but there were differences for patients with acute myeloid leukemia or diffuse large B-cell lymphoma. The association of socioeconomic status with survival for patients with acute myeloid leukemia was observed mainly during the first 2 years after diagnosis."
"Teclistamab in relapsed refractory multiple myeloma: multi-institutional real-world study"
Source
Mohan, M., Monge, J., Shah, N. et al. Teclistamab in relapsed refractory multiple myeloma: multi-institutional real-world study. Blood Cancer J. 14, 35 (2024). https://doi.org/10.1038/s41408-024-01003-z. March 5, 2024.
Overview
From the study: "The objective of our study was to report real-world data on the safety and efficacy of standard-of-care teclistamab in patients with relapsed/refractory multiple myeloma (MM). This is a multi-institutional retrospective cohort study and included all consecutive patients that received at least one dose of teclistamab up until August 2023.."
"Adverse effects and non-relapse mortality of BCMA directed T cell therapies in multiple myeloma: an FAERS database study"
Source
Gong, Z., Umoru, G., Monge, J. et al. Adverse effects and non-relapse mortality of BCMA directed T cell therapies in multiple myeloma: an FAERS database study. Blood Cancer J. 14, 36 (2024). https://doi.org/10.1038/s41408-024-01023-9. March 5, 2024.
Overview
This study analyzes "the most reported adverse events and NRM among the FDA-approved BCMA-directed immunotherapy in multiple myeloma."
"GZ17-6.02 interacts with proteasome inhibitors to kill multiple myeloma cells"
Source
Booth L., Roberts J. L., West C., Dent P. GZ17-6.02 interacts with proteasome inhibitors to kill multiple myeloma cells. Oncotarget. 2024; 15: 159-174. Retrieved from https://www.oncotarget.com/article/28558/text/. March 6, 2024.
Overview
A new drug called GZ17-6.02, made in a lab, has been tested in people with solid tumors in a phase I study. The recommended dose for the next phase of testing is 375 mg taken by mouth twice a day.
When used alone, GZ17-6.02 was better at killing cells of a type of cancer called multiple myeloma than it was at killing other types of solid tumor cells.
When combined with other drugs that target proteasomes, GZ17-6.02 worked even better at killing multiple myeloma cells, including ones that were resistant to the other drugs.
The combination of GZ17-6.02 and Velcade (bortezomib) changed the way certain proteins work inside the cells, which helped kill the cancer cells. It also increased a process called autophagy, which is like cleaning up the cell, and this was important for killing the tumor cells.
Further tests in animals with multiple myeloma are needed to confirm these findings and see if the treatment works as well in living organisms as it does in lab dishes.
"Enhancing prognostic power in multiple myeloma using a plasma cell signature derived from single-cell RNA sequencing"
Source
Li, Jr., Arsang-Jang, S., Cheng, Y. et al. Enhancing prognostic power in multiple myeloma using a plasma cell signature derived from single-cell RNA sequencing. Blood Cancer J. 14, 38 (2024). https://doi.org/10.1038/s41408-024-01024-8 March 6, 2024.
Overview
Current methods of predicting outcomes for multiple myeloma have limitations. By studying individual cells, researchers created a new way to predict how the disease will progress. They looked at data from 2115 samples, including those from people with multiple myeloma, pre-cancerous conditions, and healthy individuals. They found that higher scores from their new test were linked to more advanced stages of the disease and shorter survival times for people with multiple myeloma. This link held true regardless of other methods used to predict outcomes.
This analysis also showed that higher scores were associated with specific genetic changes and alterations in the immune system within the tumors. These findings suggest that this new test could help doctors better predict how multiple myeloma will progress and guide decisions about treatment.
"Waking up exhausted BCMA-specific T cells in myeloma"
Source
Sacco, A., Roccaro, A.M., Waking up exhausted BCMA-specific T cells in myeloma. Blood (2024) 143 (10): 840–841. https://doi.org/10.1182/blood.2023023037. March 7, 2024.
Overview
This study discusses how researchers "have developed a well-defined, robust, and scientifically sound proof-of-principle platform to epigenetically reprogram BCMA-specific CD8+ memory cytotoxic T lymphocytes as a promising strategy to promote an efficacious and long-term anti-multiple myeloma immunity."
"Health-related quality of life in patients with hematologic malignancies treated with chimeric antigen receptor T-cell therapy: review and current progress"
Source
Tchernonog E, Moignet A, Anota A, Bernard S, Bouguet G, Colin F, Rioufol C, Ysebaert L, Gyan E. Health-related quality of life in patients with hematologic malignancies treated with chimeric antigen receptor T-cell therapy: review and current progress. Haematologica; https://doi.org/10.3324/haematol.2022.282363 [Early view]. March 7, 2024.
Overview
Researchers "conducted a literature search up to June 2023 to identify the health-related quality of life (HRQoL) tools used in clinical trials and in real-world studies investigating CAR T-cell therapy in patients with lymphomas or leukemias."
This research summarizes "the most commonly used CAR T-cell specific and non-specific HRQoL tools and discusses how the use of HRQoL and other patient-reported outcome tools may be optimized."
"C-terminal binding protein (CTBP2) is a novel tumor suppressor targeting the MYC-IRF4 axis in multiple myeloma"
Source
Cheung, C.H.Y., Cheng, C.K., et al. C-terminal binding protein (CTBP2) is a novel tumor suppressor targeting the MYC-IRF4 axis in multiple myeloma. Blood Adv bloodadvances.2023010218. https://doi.org/10.1182/bloodadvances.2023010218 March 8, 2024.
Overview
The following are key points of this study:
- "Frequent epigenetic downregulation of CTBP2 is associated with adverse clinicopathological features in multiple myeloma.
- CTBP2 represses the pro-survival MYC-IRF4 axis and its restoration elicits potent anti-myeloma effects."
"Redefining high-risk multiple myeloma with an APOBEC/Inflammation-based classifier"
Source
Grasedieck, S., Panahi, A., Jarvis, M.C. et al. Redefining high-risk multiple myeloma with an APOBEC/Inflammation-based classifier. Leukemia (2024). https://doi.org/10.1038/s41375-024-02210-0 March 9, 2024.
Overview
From the study: "In this study, we have developed the EI-score which serves as an important proof-of-concept, demonstrating that inclusion of molecular markers that reflect disease progression can improve multiple myeloma risk assessment. Although our data highlights the limitations of cytogenetics-based risk stratifiers, ISS, R-ISS and R2-ISS represent the current clinical standard due to their accessibility. Eventually, the development of more contemporary stratification systems will be necessary to improve risk- and treatment stratifications of multiple myeloma patients."
"Differentiation of BCMA-specific induced pluripotent stem cells into rejuvenated CD8αβ+ T cells targeting multiple myeloma"
Source
Bae, J., et.al. Differentiation of BCMA-specific induced pluripotent stem cells into rejuvenated CD8αβ+ T cells targeting multiple myeloma. Blood (2024) 143 (10): 895–911. https://doi.org/10.1182/blood.2023020528. March 7, 2024.
Overview
The following are key points from this study:
- "A preclinical framework to epigenetically reprogram BCMA-specific CD8αβ+ memory T cells using iPSC technology to target multiple myeloma.
- BCMA-specific iPSC–derived hematopoietic progenitor cells having specific regulatory elements that control CD8+ T-cell lineage commitment."
"Pain Management in Multiple Myeloma Patients: A Literature Review"
Source
Rana S, Maharjan S, Sookdeo S D, et al. (March 11, 2024) Pain Management in Multiple Myeloma Patients: A Literature Review. Cureus 16(3): e55975. doi:10.7759/cureus.55975 March 11, 2024.
Overview
Cancer patients with multiple myeloma often struggle with managing pain, which can be quite challenging. This review thoroughly examines the current strategies for treating pain in these patients and discusses the difficulties faced in doing so. It looks at both medication-based and non-medication-based approaches to managing pain.
In the future, there are promising areas for further research and development, such as using precision medicine to tailor pain management to individual patients and exploring new types of treatments. Despite some limitations, advancements in pain management offer hope for improving the quality of life and overall outcomes for multiple myeloma patients.
"Large differences in age-specific survival in multiple myeloma in the Nordic countries"
Source
Hemminki, K., Zitricky, F., Försti, A. et al. Large differencies in age-specific survival in multiple myeloma in the nordic countries. Blood Cancer J. 14, 43 (2024). https://doi.org/10.1038/s41408-024-01026-6 March 11, 2024.
Overview
Treating multiple myeloma has advanced quickly, with new therapies introduced. In the late 1980s, a treatment called autologous stem cell transplantation (ASCT) was used alongside high-dose melphalan. At first, only patients under 65 were considered, but now it's extended to those up to 70 or 75. In Nordic countries, around 30% of MM patients get this treatment. Newer treatments, like thalidomide, lenalidomide, and bortezomib, have changed how multiple myeloma is managed. Even older patients respond well to treatment, despite having more advanced disease.
Survival rates for multiple myeloma have gotten better in Sweden and the USA, but older patients still don't survive as well as younger ones. Because some treatments are only suitable for younger, healthier patients, it's important to look at how different age groups fare. Recent data from the NORDCAN database allows us to compare survival rates across different age groups and countries. This helps us understand why survival rates vary between countries.
"Talquetamab in multiple myeloma"
Source
Liu L, Krishnan A. Talquetamab in multiple myeloma. Haematologica 2023;109(3):718-724; https://doi.org/10.3324/haematol.2023.283931.
Overview
From the abstract: This study concludes that "talquetamab represents yet another T-cell redirection option for patients with relapsed/refractory multiple myeloma. Future trials are ongoing to answer the question of optimal sequencing of these T-cell redirecting therapies as well as optimal combinations."
"Idecabtagene vicleucel chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma with renal impairment"
Source
Sidana S, Peres LC, Hashmi H, Hosoya H, Ferreri C, Khouri J, Dima D, Atrash S, Voorhees P, Simmons G, Sborov DW, Kalariya N, Hovanky V, Bharadwaj S, Miklos D, Wagner C, Kocoglu MH, Kaur G, Davis JA, Midha S, Janakiram M, Freeman C, Alsina M, Locke F, Gonzalez R, Lin Y, McGuirk J, Afrough A, Shune L, Patel KK, Hansen DK. Idecabtagene vicleucel chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma with renal impairment. Haematologica 2023;109(3):777-786; https://doi.org/10.3324/haematol.2023.283940.
Overview
In this study, researchers "evaluated patients with relapsed multiple myeloma with renal impairment (RI) treated with standard of care idecabtagene vicleucel (ide-cel), as outcomes with chimeric antigen receptor (CAR) T-cell therapy are unknown in this population."
"The changing spectrum of infection with BCMA and GPRC5D targeting bispecific antibody (bsAb) therapy in patients with relapsed refractory multiple myeloma"
Source
Hammons L, Szabo A, Janardan A, Bhatlapenumarthi V, Annyapu E, Dhakal B, Al Hadidi S, Radhakrishnan SV, Narra R, Bhutani D, Thanendrarajan S, Janz S, Zangari M, Lentzsch S, van Rhee F, Crescencio JCR, D’Souza A, Chakraborty R, Mohan M, Schinke C. The changing spectrum of infection with BCMA and GPRC5D targeting bispecific antibody (bsAb) therapy in patients with relapsed refractory multiple myeloma. Haematologica 2023;109(3):906-914; https://doi.org/10.3324/haematol.2023.283590.
Overview
This study reports on infection-related toxicities that are "a significant burden in patients with relapsed/refractory multiple myeloma who were treated with bispecific antibodies." It concludes that "infection-related morbidity and mortality is a clinically significant adverse effect of bispecific antibodies in multiple myeloma."
"Treatment pattern and outcomes of re-induction therapy prior to stem cell transplantation in patients with relapsed/refractory multiple myeloma in Germany"
Source
Sauer, S., Engelhardt, M., Trautmann-Grill, K. et al. Treatment pattern and outcomes of re-induction therapy prior to stem cell transplantation in patients with relapsed/refractory multiple myeloma in Germany. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02208-3 March 14, 2024.
Overview
In Germany, this study shows that for patients with relapsed or refractory multiple myeloma (RRMM), undergoing salvage stem cell transplantation (SCT) after re-induction therapy, especially with treatments containing carfilzomib, can be beneficial. A group of mostly healthy patients under 70 years old, who responded well to initial treatment, seemed to benefit from this approach in second or third-line therapy. Even though lenalidomide maintenance is typically approved only for first-line therapy, it may help patients in later stages if they still respond to similar drugs. New treatments, like carfilzomib combined with daratumumab or isatuximab, provide more options for RRMM therapy. Other promising treatments, like iberdomide and chimeric antigen receptor T-cell therapies, are being studied for patients who don't respond to lenalidomide. As more options become available, real-world data like ours are important for understanding their effects on patient care.
"Thromboembolic risk of carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for newly diagnosed multiple myeloma: A comparative systematic review and meta-analysis."
Source
Costa BA, Costa TA, Saravia SD, et al. Thromboembolic risk of carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for newly diagnosed multiple myeloma: A comparative systematic review and meta-analysis. Am J Hematol. 2024; 1-10. doi:10.1002/ajh.27288
Overview
In individuals with multiple myeloma, blood clotting, known as thrombosis, is a common and sometimes serious problem. It can be caused by the disease itself or the treatments used.
Researchers looked at whether a combination treatment of Kyprolis (carfilzomib), Revlimid (lenalidomide), and dexamethasone (KRd) or Velcade (bortezomib), Revlimid (lenalidomide), and dexamethasone (VRd) had different risks for blood clots. They studied 2304 patients with newly diagnosed MM and found that VRd had lower rates of venous blood clots compared to KRd. However, both treatments had similar rates of arterial blood clots. Because the studies were retrospective and had limitations, more research is needed to confirm these findings and improve how to prevent blood clots in multiple myeloma.
"Second Primary Malignancies After Commercial CAR T Cell Therapy: Analysis of FDA Adverse Events Reporting System (FAERS)"
Source
Elsallab, M., Ellithi, M., et al. Second Primary Malignancies After Commercial CAR T Cell Therapy: Analysis of FDA Adverse Events Reporting System (FAERS). Blood blood.2024024166. https://doi.org/10.1182/blood.2024024166 March 14, 2024
Overview
From the abstract: "Second primary malignancies (SPMs) were reported in 536 out of 12,394 (4.3%) adverse event reports following CAR T-cell therapies in the FDA Adverse Event Reporting System (FAERS). Myeloid and T-cell neoplasms were disproportionately more frequently reported, warranting further follow-up."
"Progression-free survival of myeloma patients who become IFE-negative correlates with the detection of residual monoclonal free light chain (FLC) by mass spectrometry"
Source
Giles, H.V., Drayson, M.T., Kishore, B. et al. Progression-free survival of myeloma patients who become IFE-negative correlates with the detection of residual monoclonal free light chain (FLC) by mass spectrometry. Blood Cancer J. 14, 50 (2024). https://doi.org/10.1038/s41408-024-00995-y March 18, 2024.
Overview
In patients with myeloma, deeper responses to treatment are linked to better survival. But current blood tests have limitations in detecting how well the treatment is working. Previous studies suggested that when certain blood test results return to normal after treatment, it may mean better outcomes for patients. However, recent research has questioned this idea.
A new method called mass spectrometry (MS)-based assessment of free light chains (FLC) in the blood may offer a more accurate way to detect abnormal proteins related to myeloma. To test this, samples from patients treated with a specific combination of drugs underwent FLC-MS testing. Results showed that nearly 40% of patients had different results with this new method compared to the standard test. Some patients who were considered negative by the standard test actually had abnormal proteins detectable by FLC-MS.
Patients who tested positive with FLC-MS were found to have a higher risk of their disease progressing sooner, compared to those who tested negative. This study suggests that FLC-MS is better at detecting abnormal proteins in myeloma patients, helping to identify those at risk of progression early on.
"The bone ecosystem facilitates multiple myeloma relapse and the evolution of heterogeneous drug resistant disease"
Source
Bishop, R.T., Miller, A.K., Froid, M. et al. The bone ecosystem facilitates multiple myeloma relapse and the evolution of heterogeneous drug resistant disease. Nat Commun 15, 2458 (2024). https://doi.org/10.1038/s41467-024-46594-0 March 19, 2024.
Overview
This study discusses multiple myeloma (MM) and how it weakens bones, which is hard to cure because some cells become resistant to treatment. Understanding how and when these resistant cells develop is tough with current methods. Researchers created a new computer model to simulate how multiple myeloma cells interact with the bone environment over time. Their findings suggest that while myeloma cells themselves play a role in becoming resistant to treatment, the bone environment also protects these cells, making them harder to kill. The model predicts that targeting this bone protection could improve treatment by getting rid of sensitive cells near the bone, which was supported by real-life experiments. This model helps scientists understand how multiple myeloma evolves in the bone and could lead to better treatments to delay the cancer from coming back.
"Impact of diagnostic investigations in the management of CAR T-cell-associated neurotoxicity"
Source
Mauget, M., Lemercier, S., Quelvin, Q., et al. Impact of diagnostic investigations in the management of CAR T-cell-associated neurotoxicity. Blood Adv bloodadvances.2023011669. https://doi.org/10.1182/bloodadvances.2023011669 March 19, 2024.
Overview
The following are key points from this study:
- Data from a large cohort of CAR-T cells-treated patients questions guidelines regarding diagnostic investigations in ICANS management.
- Our results emphasize for the first time the role of EEG in the current guidelines, but questions the need for systematic MRI and lumber puncture (LP).
"Steroid-free combination of 5-azacytidine and venetoclax for the treatment of multiple myeloma"
Source
Flanagan, L., Coughlan, A., Cosgrove, N., et al. Steroid-free combination of 5-azacytidine and venetoclax for the treatment of multiple myeloma. Haematologica Early view Mar 21, 2024 https://doi.org/10.3324/haematol.2023.283771
Overview
While myeloma survival rates have improved, treatments tailored to individual risks are still needed. Some multiple myeloma patients depend on a protein called BCL-2 for survival. Venetoclax, a drug that targets BCL-2, has shown promise in certain MM cases, but it only works for a small number of patients. Scientists aimed to find ways to make venetoclax effective for more patients. They tested various compounds and found that a drug called 5-azacytidine enhanced the effects of venetoclax in multiple myeloma cells. Further studies revealed that this combination works by increasing a protein called NOXA, which helps kill cancer cells. Importantly, adding a steroid to the treatment did not improve results and even harmed immune cells. Testing on samples from myeloma patients showed that 5-azacytidine could boost the effectiveness of venetoclax across different genetic backgrounds. This research suggests that combining 5-azacytidine with venetoclax could be a viable treatment option, especially for older myeloma patients who may benefit from a steroid-free regimen.
"Coping in patients with hematologic malignancies undergoing hematopoietic cell transplantation"
Source
Newcomb, R., Amonoo, H.L., Nelson, A.M., et al. Coping in patients with hematologic malignancies undergoing hematopoietic cell transplantation. Blood Adv (2024) 8 (6): 1369–1378. https://doi.org/10.1182/bloodadvances.2023011081 March 26, 2024.
Overview
The following are key points of this study:
- "Coping strategies before hematopoietic cell transplantation (HCT) are associated with pre-HCT quality-of-life and psychological distress.
- Supportive care interventions during HCT to promote approach-oriented coping and to mitigate avoidant coping are needed."
"Targeting CXCR4, VLA-4, and CXCR2 for hematopoietic stem cell mobilization"
Source
Cancilla, D., Rettig, M.P., Karpova, D., et al. Targeting CXCR4, VLA-4, and CXCR2 for hematopoietic stem cell mobilization. Blood Adv (2024) 8 (6): 1379–1383. https://doi.org/10.1182/bloodadvances.2023011653 March 26, 2024.
Overview
In this study, researchers "designed a novel PEGylated VLA4 inhibitor, SLU-2609, that effectively inhibits interaction of the receptor with VCAM-1 in vitro and mobilizes high levels of hematopoietic stem and progenitor cells (HSPCs) in combination with plerixafor and tGro-β. This triple combination regimen was well tolerated (no observed toxicities) and outperformed granulocyte colony-stimulating factor (G-CSF) in in vivo mobilization assays, as well as in the competitive transplant setting. Thus, not only did this combination mobilize more HSPCs than G-CSF, but it did so in a drastically reduced time frame of hours compared with days required for G-CSF mobilization.
"Exploring Indicators of Vulnerability in Older Adults With Newly Diagnosed Multiple Myeloma"
Source
Tanya M. Wildes, Exploring Indicators of Vulnerability in Older Adults With Newly Diagnosed Multiple Myeloma. JCO Clin Cancer Inform 8, e2400013(2024). DOI:10.1200/CCI.24.00013 March 20, 2024.
Overview
Through this study, researchers "have pioneered the use of the SEER-Medicare—OASIS data linkage* to demonstrate that older adults who have received home health services in the year before diagnosis had poorer survival than those who did not, and among these individuals, the severity of disability is associated with treatment receipt, intensity of treatment, health care utilization, and mortality. Future work to refine the subgroups by disability and exploring additional vulnerabilities, including social frailty, cognitive and sensory impairments, and falls, will likely help us improve the care of older adults with multiple myeloma by identifying those who will benefit from additional support and guide treatment recommendations on the basis of personalized risk and preference assessment."
*This is the "first peer-reviewed publication using a newly available linkage of the SEER-Medicare database with data to the Outcome and Assessment Information Set (OASIS) to examine outcomes in an individual malignancy."
"Once-weekly versus twice-weekly bortezomib in newly diagnosed multiple myeloma: a real-world analysis"
Source
Hoff, F.W., Banerjee, R., Khan, A.M. et al. Once-weekly versus twice-weekly bortezomib in newly diagnosed multiple myeloma: a real-world analysis. Blood Cancer J. 14, 52 (2024). https://doi.org/10.1038/s41408-024-01034-6 March 22, 2024
Overview
In this study, researchers "analyze the real-world prevalence and efficacy of once-weekly versus twice-weekly bortezomib regimens in newly diagnosed multiple myeloma."
"Outcomes of patients with multiple myeloma refractory to standard dose vs low dose lenalidomide"
Source
Goel, U., Charalampous, C., Kapoor, P. et al. Outcomes of patients with multiple myeloma refractory to standard dose vs low dose lenalidomide. Blood Cancer J. 14, 55 (2024). https://doi.org/10.1038/s41408-024-01039-1 March 26, 2024.
Overview
In multiple myeloma, resistance to Revlimid (lenalidomide) is a crucial factor when deciding on treatment after the disease comes back. It's not clear if resistance to lenalidomide differs between myeloma patients who were given standard doses or lower maintenance doses. This study looked at how patients responded to further treatment after becoming resistant to either standard or low doses of lenalidomide.
Researchers reviewed myeloma patients who had received lenalidomide-based treatments as their first line of therapy. They compared how long patients stayed without their disease getting worse (progression-free survival, or PFS) and how long they survived overall after starting second-line treatment or after lenalidomide was tried again.
The study found that there was no difference in PFS between patients who were resistant to standard doses of lenalidomide compared to those resistant to low doses. However, both groups had shorter PFS compared to patients who weren't resistant to lenalidomide. Similar trends were observed when patients were retreated with lenalidomide. These findings suggest that lenalidomide resistance doesn't depend on the dose used, and whether a patient is considered resistant should not be based on the dose they received.
"BCMA- or GPRC5D-targeting bispecific antibodies in multiple myeloma: efficacy, safety, and resistance mechanisms"
Source
Holly Lee, Paola Neri, Nizar J. Bahlis; BCMA- or GPRC5D-targeting bispecific antibodies in multiple myeloma: efficacy, safety, and resistance mechanisms. Blood 2024; 143 (13): 1211–1217. doi: https://doi.org/10.1182/blood.2023022499.
Overview
From the abstract: "Bispecific antibodies that engage T cells to target B-cell maturation antigen or G-protein–coupled receptor class C group 5 member D have demonstrated remarkable efficacy in heavily pretreated relapsed or refractory multiple myeloma (MM), leading to the recent accelerated approval of teclistamab, elranatamab, and talquetamab by health agencies. Future challenges, however, remain to define their optimal dosing schedule and duration, sequencing, and integration with established anti-MM therapeutics as well as delineating the biological and clinical mediators of immune escape."
"BA p53 score derived from TP53 CRISPR/Cas9 HMCLs predicts survival and reveals a major role of BAX in the response to BH3 mimetics"
Source
Romane Durand, Géraldine Descamps, Céline Bellanger, Christelle Dousset, Sophie Maïga, Jean-Baptiste Alberge, Jennifer Derrien, Jonathan Cruard, Stéphane Minvielle, Nicoletta Libera Lilli, Catherine Godon, Yannick Le Bris, Benoit Tessoulin, Martine Amiot, Patricia Gomez-Bougie, Cyrille Touzeau, Philippe Moreau, David Chiron, Agnès Moreau-Aubry, Catherine Pellat-Deceunynck; A p53 score derived from TP53 CRISPR/Cas9 HMCLs predicts survival and reveals a major role of BAX in the response to BH3 mimetics. Blood 2024; 143 (13): 1242–1258. doi: https://doi.org/10.1182/blood.2023021581 March 28, 2024.
Overview
This study examines the following:
- "A functional p53 score identifies cells with biallelic TP53 invalidation and predicts survival in myeloma.
- p53-regulated BAX, but not BAK, expression governs the death response to BH3 mimetics"
"TP53 function over forms in multiple myeloma"
Source
Paola Neri, Lawrence H. Boise; TP53 function over forms in multiple myeloma. Blood 2024; 143 (13): 1202–1204. doi: https://doi.org/10.1182/blood.2023023487 March 28, 2024
Overview
In this study, researchers "describe a functional score that identifies cells with loss of TP53 and demonstrate a role for TP53 function in the response to BH3 mimetics in multiple myeloma."