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 January 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 January 2024)
"Impact of viral hepatitis therapy in multiple myeloma and other monoclonal gammopathies linked to hepatitis B or C viruses"
Source
Rodríguez-García A, Mennesson N, Hernandez-Ibarburu G, Morales ML, Garderet L, Bouchereau L, Allain-Maillet S, Piver E, Marbán I, Rubio D, Bigot-Corbel E, Martínez-López J, Linares M, Hermouet S. “Impact of viral hepatitis therapy in multiple myeloma and other monoclonal gammopathies linked to hepatitis B or C viruses”. Haematologica. January 1, 2024;109(1):272-282. DOI: 10.3324/haematol.2023.283096. PMID: 37199121; PMCID: PMC10772493
Overview
In this study, researchers explored the link between hepatitis B virus (HBV) infection and the development of monoclonal gammopathies, including multiple myeloma (MM) and monoclonal gammopathies of undetermined significance (MGUS). They focused on 45 HBV-infected patients with monoclonal gammopathy and found that 40% had a monoclonal immunoglobulin specifically targeting HBV. Two patients with HBV-targeted gammopathy received antiviral treatment (AVT), and their condition did not progress. The study then assessed AVT efficacy in a large cohort of HBV-infected MM patients, comparing them to HCV-infected MM patients. The results showed that AVT significantly improved overall survival probability for both HBV and HCV-positive cohorts. This research suggests that MGUS and MM in infected individuals may be driven by HBV or HCV, emphasizing the importance of antiviral treatment in managing these conditions.
"Thrombotic Risk and Calculated Whole Blood Viscosity in a Cohort of Patients With New Diagnosis of Multiple Myeloma"
Source
Carlisi M, Lo Presti R, Mancuso S, Siragusa S, Caimi G. Thrombotic risk and calculated whole blood viscosity in a cohort of patients with new diagnosis of multiple myeloma. Clin Appl Thromb Hemost. 2024;30:10760296231222477. doi:10.1177/10760296231222477. January 3, 2024.
Overview
This study explores why blood clots happen in multiple myeloma (MM) patients involve many factors related to the patients and the disease itself. To improve how researchers handle this health issue, tools have been developed to identify the risk accurately. The study focused on the thickness of blood, known as blood viscosity, as a factor in higher clotting events. Researchers examined a group of patients with a new MM diagnosis to see if there was a connection between blood viscosity and the risk of blood clots. The findings suggest that when using the IMPEDE Venous Thromboembolic Event (VTE) score to assess clotting risk, individuals with a higher risk show increased blood viscosity. However, this connection wasn't observed when using the IMWG/NCCN guidelines for risk assessment. Although the study is small and looks back at past information, it represents an essential first step. More extensive studies are needed to confirm the role of blood thickness in assessing the risk of blood clots in MM patients.
"Belantamab mafodotin, pomalidomide and dexamethasone in refractory multiple myeloma: a phase 1/2 trial"
Source
Trudel, S., McCurdy, A., Louzada, M.L. et al. Belantamab mafodotin, pomalidomide and dexamethasone in refractory multiple myeloma: a phase 1/2 trial. Nat Med (2024). https://doi.org/10.1038/s41591-023-02703-y January 4, 2024.
Overview
To find more effective treatments for relapsed multiple myeloma, the ALGONQUIN trial explored the combination of the anti-BCMA antibody–drug conjugate belantamab mafodotin with pomalidomide and dexamethasone. The study, focusing on patients resistant to lenalidomide and exposed to proteasome inhibitors, revealed promising outcomes. Among 87 patients with a median of three prior regimens, 55.2% were triple-class refractory. The regimen's recommended dose exhibited an overall response rate of 85.3%, with 75.7% achieving a very good partial response. At a median follow-up of 13.9 months, the estimated two-year progression-free survival was 52.8%. Despite common adverse events like visual acuity reduction and keratopathy, the schedule showed manageable corneal effects without compromising efficacy. The trial's success prompts further investigation in the phase 3 DREAMM-8 study, aiming to confirm the durability of responses and overall survival with belantamab mafodotin plus pomalidomide and dexamethasone in relapsed multiple myeloma.
"Association of proton pump inhibitor use with survival and adverse effects outcomes in patients with multiple myeloma: pooled analysis of three clinical trials"
Source
Almansour, S.A., Alqudah, M.A.Y., Abuhelwa, Z. et al. Association of proton pump inhibitor use with survival and adverse effects outcomes in patients with multiple myeloma: pooled analysis of three clinical trials. Sci Rep 14, 591 (2024). https://doi.org/10.1038/s41598-023-48640-1. January 5, 2024.
Overview
Proton pump inhibitors (PPIs), commonly used in cancer patients, were investigated for their effects on treatment outcomes in multiple myeloma (MM) patients undergoing daratumumab, lenalidomide, or bortezomib combination treatments. Involving 1804 patients across three randomized-control trials, where 32% used PPIs at the beginning, the study revealed independent associations between PPI use and worse overall survival and higher-grade adverse events. The data, adjusted for various factors, showed a 32% increased risk of mortality and a 39% increased risk of severe adverse events in PPI users. Although the link with progression-free survival didn't reach statistical significance, the findings were consistent across trials and treatment arms. This study identifies PPI use as a negative prognostic factor in MM patients, influencing clinical decisions about its utilization. Despite these results, more research is needed to fully understand the impacts and safety of PPIs in the context of multiple myeloma treatment.
"Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed/refractory myeloma"
Source
Fischer, L., Grieb, N., Born, P. et al. Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed/refractory myeloma. Leukemia (2024). https://doi.org/10.1038/s41375-023-02129-y. January 6, 2024.
Overview
B-cell maturation antigen (BCMA)-targeting CAR T cell therapy has transformed the treatment of relapsed/refractory multiple myeloma (RRMM). Yet, understanding how these CAR T cells behave in patients and their connection to treatment response, resistance, and side effects remains limited. Analyzing 27 RRMM patients treated with Ide-cel, a BCMA-targeting CAR T cell therapy, researchers used flow cytometry to examine the expansion, persistence, and impact on bystander cells of these cells. They discovered that the in vivo expansion of CD8+ CAR T cells is linked to treatment response, while persistence is not crucial for lasting remission. Additionally, a higher fraction of CD8+ T cells during leukapheresis, combined with successful lymphodepletion, positively influences outcomes. The study also identified factors that predict higher-grade cytokine release syndrome (CRS) before lymphodepletion. This detailed analysis enhances our understanding of BCMA-targeting CAR T cell dynamics, aiding in predicting individual patient responses and managing side effects early in RRMM treatment.
"Neutrophil activation and clonal CAR-T re-expansion underpinning cytokine release syndrome during ciltacabtagene autoleucel therapy in multiple myeloma"
Source
Yang, S., Xu, J., Dai, Y. et al. Neutrophil activation and clonal CAR-T re-expansion underpinning cytokine release syndrome during ciltacabtagene autoleucel therapy in multiple myeloma. Nat Commun 15, 360 (2024). https://doi.org/10.1038/s41467-023-44648-3. January 8, 2024.
Overview
Cytokine release syndrome (CRS) poses a significant challenge in chimeric antigen receptor redirected T cells (CAR-T) therapy for relapsed/refractory multiple myeloma patients. Studying 26 patients treated with ciltacabtagene autoleucel, researchers monitored serum cytokine levels and immune cell transcriptomes to understand CRS's immunological dynamics. They observed that, before severe symptoms, neutrophil activation peaked, while T lymphocytes and monocytes were the primary cytokine sources during manifest CRS. Activation of the JAK/STAT pathway preceded cytokine release, offering insight into CRS onset. The study suggests that temporal cytokine secretion patterns accurately describe CRS severity, potentially enabling prediction. Additionally, CAR-T re-expansion was identified in three patients, emphasizing the need for careful monitoring, especially in cases with unique genetic characteristics and potential lethal risks. These findings highlight a latent phase before CRS manifestation, providing opportunities for timely therapeutic interventions and emphasizing the importance of monitoring CAR-T re-expansion to enhance patient safety.
"Deciphering racial disparities in multiple myeloma outcomes"
Source
Kimberly A. Bertrand, Raphael Szalat. Deciphering racial disparities in multiple myeloma outcomes. Blood Adv (2024) 8 (1): 234–235. https://doi.org/10.1182/bloodadvances.2023011457. January 9, 2024.
Overview
This recent study published in Blood Advances delves into the impact of diabetes and obesity on the survival of multiple myeloma patients, particularly focusing on racial disparities. The study, covering 26 patients across two academic medical centers, revealed that preexisting diabetes negatively affected overall survival in White patients but not in Black patients. Additionally, an elevated body mass index (BMI) was associated with improved survival, with this effect more pronounced in Black patients. Notably, even after accounting for diabetes and obesity, White patients exhibited better overall survival than Black patients. The research sheds light on the complexity of factors influencing multiple myeloma outcomes, indicating that understanding racial disparities requires a comprehensive evaluation beyond diabetes and obesity. The study emphasizes the need for continued efforts to innovate treatments, explore disease pathogenesis, and include diverse populations in research to ensure equitable outcomes in the evolving landscape of multiple myeloma therapy.
"Genomic Classification and Individualized Prognosis in Multiple Myeloma"
Source
Maura, F., et al. (2024) Genomic Classification and Individualized Prognosis in Multiple Myeloma. Journal of Clinical Oncology. doi.org/10.1200/JCO.23.01277. January 9, 2024.
Overview
This recent study examined diverse outcomes observed in newly diagnosed multiple myeloma (NDMM) patients, where survival can vary significantly. Analyzing data from 1,933 NDMM patients with clinical, genomic, and treatment information, researchers identified 12 distinct groups based on genomic drivers. Going beyond previous classifications, they created an individualized risk-prediction model called IRMMa by integrating clinical, genomic, and treatment variables, considering factors like high-dose melphalan followed by autologous stem-cell transplantation (HDM-ASCT) and maintenance therapy. The IRMMa model outperformed other prognostic models, showcasing higher accuracy in predicting overall survival. Key genomic features influencing the model included factors like 1q21 gain/amp, del 1p, TP53 loss, NSD2 translocations, APOBEC mutational signatures, and copy-number signatures. Importantly, the model's accuracy and superiority were validated in a separate clinical trial. The study's findings pave the way for personalized therapeutic decisions for NDMM patients, offering a groundbreaking approach to tailor treatments based on individual risks and genomic characteristics.
"Outcomes of patients with multiple myeloma and 1q gain/amplification receiving autologous hematopoietic stem cell transplant: the MD Anderson cancer center experience"
Source
Pasvolsky, O., Ghanem, S., Milton, D.R. et al. Outcomes of patients with multiple myeloma and 1q gain/amplification receiving autologous hematopoietic stem cell transplant: the MD Anderson cancer center experience. Blood Cancer J. 14, 4 (2024). https://doi.org/10.1038/s41408-023-00973-w. January 10, 2024.
Overview
In this study, the impact of additional copies of chromosome 1q (1q+) on the outcomes of patients with newly-diagnosed multiple myeloma (NDMM) undergoing autologous transplantation (autoSCT) was investigated. A retrospective analysis included 213 NDMM patients with 1q21 gain/amplification who received autoSCT between 2008–2018. The majority had 1q gain (79%), while 21% had 1q amplification. The common induction regimen was bortezomib, lenalidomide, and dexamethasone. Post-autoSCT, 78% and 87% achieved ≥VGPR (Very Good Partial Response) at day 100 and best response, and 38% and 50% achieved minimal residual disease (MRD)-negative ≥VGPR, respectively. Median progression-free survival (PFS) and overall survival (OS) for the entire cohort were 35.5 months and 81.4 months. The study identified factors affecting outcomes, such as MRD negativity before autoSCT associated with superior PFS and 1q amplification linked to inferior progression-free survival (PFS). Achieving MRD-negative ≥VGPR post-transplant was associated with better overall survival (OS). In summary, patients with 1q+ NDMM, particularly 1q amplification, exhibit inferior survival outcomes post-autoSCT, though better than other high-risk cytogenetic abnormalities.
"DNTGF-βR armored CAR-T cell therapy against tumors from bench to bedside"
Source
Wang, Y., Zhao, G., Wang, S. et al. DNTGF-βR armored CAR-T cell therapy against tumors from bench to bedside. J Transl Med 22, 45 (2024). https://doi.org/10.1186/s12967-023-04829-6. January 11, 2024.
Overview
From the study: "CAR-T cell therapy has achieved great success in hematological malignancies, but its effectiveness in solid tumors has been limited due to the complicated immunosuppressive tumor microenvironment (TME). TGF-β, a negative cytokine, exerts critical roles in shaping immunosuppressive TME, thereby promoting tumor progression and resistance [1]. Thus, evolving approaches to blocking TGF-β signaling in CAR-T cell therapy have been emerging, such as combining with TGF-β-targeted neutralizing antibodies or small molecule inhibitors, directly deleting TGF-βRII via CRISPR/Cas9 technology, or co-expressing a dominant-negative TGF-β receptor II (DNTGF-βRII). As a relatively niche modification strategy, dominant negative receptor (DNR) technology has received less attention. However, its potential translational value warrants further underscore."
This study concluded the following: "DNTGF-βR entrusted CAR-T cells with a new capability to circumvent immunosuppressive TME so as to improve antitumor efficacy. Although, potential risks and challenges still remain. Most importantly, novel targets are urgent to be discovered and innovative genetic engineering strategies should be encouraged to investigate to promote their translations from bench to bedside."
"Mass spectrometry-detected MGUS is associated with obesity and other novel modifiable risk factors in a high-risk population"
Source
David J Lee, Habib El-Khoury, Angela C Tramontano, Jean-Baptiste Alberge, Jacqueline Perry, Maya I Davis, Erica Horowitz, Robert A Redd, Dhananjay Sakrikar, David Barnidge, Mark C Perkins, Stephen Harding, Lorelei Mucci, Timothy R Rebbeck, Irene M Ghobrial, Catherine R Marinac. Mass spectrometry-detected MGUS is associated with obesity and other novel modifiable risk factors in a high-risk population. Blood Adv bloodadvances.2023010843. https://doi.org/10.1182/bloodadvances.2023010843. January 11, 2024.
Overview
This study showed "Among individuals at elevated risk of multiple myeloma, obesity is positively associated with mass spectrometry-detected MGUS, and "High physical activity is inversely associated with MGUS, whereas heavy smoking and short sleep are positively associated with MGUS."
"Bone marrow adipocytes provide early sign for progression from MGUS to multiple myeloma"
Source
El-Masri B. M., Leka B., Mustapha F., Gundesen M. Tveden, Hinge M., Lund T., Andersen T. L., Diaz-delCastillo M., Jafari A. Bone marrow adipocytes provide early sign for progression from MGUS to multiple myeloma. Oncotarget. 2024; 15: 20-26. Retrieved from https://www.oncotarget.com/article/28548/text/ January 16, 2024.
Overview
Multiple myeloma's precursor stage, monoclonal gammopathy of undetermined significance (MGUS), has a 1% annual risk of progressing to MM. Identifying high-risk MGUS patients early can transform care, enhance quality of life, and impact society. This study reveals that changes in bone marrow fat (BMAT) could signal MGUS progression to MM. Using AI to analyze bone marrow biopsies from MGUS patients, researchers found that decreased bone marrow adipocyte (BMAd) density and altered BMAd size and roundness were linked to progression. Recognizing these early changes in BMAT could serve as vital indicators for MGUS to MM transition, allowing timely interventions and personalized treatments. The cost-effective and fast AI-based histological analysis proposed in this study could make this approach practical for clinical use.
"Racial differences in treatment and survival among older patients with multiple myeloma"
Source
Wang R, Neparidze N, Ma X, Colditz GA, Chang S, Wang S. Racial differences in treatment and survival among older patients with multiple myeloma. Cancer Med. 2024 Jan 17. doi: 10.1002/cam4.6915.
Overview
This study explores the impact of race on the treatment and survival outcomes of older individuals (≥66 years) diagnosed with multiple myeloma (MM) between 2007 and 2017. While advancements in MM treatments have improved overall survival, this research focuses on racial differences, specifically between non-Hispanic African American (NHAA) and non-Hispanic White (NHW) patients.
The study, using the SEER database, reveals that the proportion of NHAA patients receiving treatment within the first year after diagnosis was consistently lower than NHW patients. The difference increased from 2.9% in 2007-2009 to 6.9% in 2014-2017. Interestingly, NHAA patients who received no treatment had lower mortality rates compared to their NHW counterparts. However, among those who received treatment, both groups had similar survival rates.
The findings highlight a growing racial disparity in treatment utilization over time, emphasizing the need to address barriers hindering equal access to treatment for all MM patients. Efforts to eliminate these barriers are crucial for improving outcomes and ensuring equitable care.
"Mode of progression in smoldering multiple myeloma: a study of 406 patients"
Source
Abdallah, N.H., Lakshman, A., Kumar, S.K. et al. Mode of progression in smoldering multiple myeloma: a study of 406 patients. Blood Cancer J. 14, 9 (2024). https://doi.org/10.1038/s41408-024-00980-5. January 17, 2024.
Overview
In this study, researchers examined how clinicians approach patients with high-risk smoldering multiple myeloma (SMM), a precursor to multiple myeloma (MM). The study included 406 patients diagnosed with SMM between 2013–2022 at Mayo Clinic, Rochester, MN. For those at high risk, not treated during the SMM phase (71 patients), 51 progressed by the last follow-up. The events leading to MM diagnosis included bone lesions (37%), anemia (35%), hypercalcemia (8%), and renal failure (6%). Some patients met MM criteria based on marrow plasmacytosis or free light chain ratio, and 45% had clinically significant events. MM diagnosis resulted from routine surveillance (45%), provider suspicion (14%), bone pain (20%), and hospitalization/emergency visits (4%). In 14%, the presentation was not documented. The study emphasizes that a significant proportion of high-risk SMM patients on surveillance develop organ damage, and routine testing may miss some progressing cases.
"The impact of social vulnerability index on survival following autologous stem cell transplant for multiple myeloma"
Source
Salafian, K., Mazimba, C., Volodin, L. et al. The impact of social vulnerability index on survival following autologous stem cell transplant for multiple myeloma. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02200-x January 18, 2024.
Overview
This study investigates the impact of social determinants of health, specifically the CDC Social Vulnerability Index (SVI), on the outcomes of multiple myeloma (MM) patients undergoing autologous hematopoietic stem cell transplantation (ASCT).
The research involved 225 multiple myeloma (MM)patients who underwent ASCT, with 51% having the procedure in the last 5 years. Five years after the transplant, 50% achieved progression-free survival (PFS), and 60% remained alive. The study found that higher SVI values were associated with lower odds of PFS and overall survival (OS) post-transplant. Greater vulnerability scores in socioeconomic status, household characteristics, and racial and ethnic minority status significantly worsened the odds of PFS.
These findings suggest that areas with high SVI may require additional resources to achieve optimal PFS and OS for MM patients undergoing ASCT. Future studies will delve into specific factors within socioeconomic status, household characteristics, and racial and ethnic minority themes, as these have a more pronounced effect on PFS.
"Bispecific BCMA/CD24 CAR-T cells control multiple myeloma growth"
Source
Sun, F., Cheng, Y., Wanchai, V. et al. Bispecific BCMA/CD24 CAR-T cells control multiple myeloma growth. Nat Commun 15, 615 (2024). https://doi.org/10.1038/s41467-024-44873-4. January 19, 2024.
Overview
Researchers are exploring a promising treatment for multiple myeloma using chimeric antigen receptor (CAR) T-cell therapies that target a specific protein called B cell maturation antigen (BCMA). While these CAR-T therapies show high response rates in myeloma, long-term cures are rare, possibly due to a small subset of residual myeloma cells that can cause relapse.
This study introduces a novel approach by developing CAR-T cells that specifically target a marker called CD24 on myeloma cells. CD24-positive myeloma cells, which often remain after BCMA-CAR-T treatment, possess less-differentiated features and express stem-like genes. The newly developed CD24-CAR-T cells work by blocking the CD24-Siglec-10 pathway, enhancing the clearance of myeloma cells by macrophages. Furthermore, CD24-CAR-T cells promote a specific type of macrophage activity associated with anti-tumor effects.
The researchers tested a dual-targeted CAR-T therapy, combining BCMA and CD24 targeting, and found it to be more effective than the monospecific BCMA-CAR-T therapy. This innovative immunotherapeutic approach aims to eliminate residual myeloma cells and enhance the immune system's ability to clear tumor cells, providing a potential advancement in multiple myeloma treatment.
"Real-world analysis of teclistamab in 123 RRMM patients from Germany"
Source
Riedhammer, C., Bassermann, F., Besemer, B. et al. Real-world analysis of teclistamab in 123 RRMM patients from Germany. Leukemia (2024). https://doi.org/10.1038/s41375-024-02154-5. January 20, 2024.
Overview
Teclistamab, a treatment for relapsed and refractory multiple myeloma (RRMM), was assessed in a real-world setting to understand its effectiveness and safety. The study involved 123 patients from 18 German centers, most with triple-class or penta-drug refractory disease. About 37% had prior BCMA-directed treatments, including CAR-T cell therapy. After a follow-up of 5.5 months, teclistamab showed an overall response rate (ORR) of 59.3% and a median progression-free survival (PFS) of 8.7 months.
Subgroup analyses revealed lower ORR and median PFS in patients with extramedullary disease, an advanced disease stage (ISS 3), and those previously treated with CAR-T therapy. Despite these differences, the duration of response in CAR-T pretreated patients was comparable to those without prior anti-BCMA therapy.
Common side effects included infections and significant blood cell count decreases. Overall, teclistamab demonstrated effectiveness and safety similar to its performance in the initial trial, highlighting its potential as a real-world treatment option for RRMM.
"Genome-wide CRISPR/Cas9 screen identifies regulators of BCMA expression on multiple myeloma cells"
Source
Ajore, R., Mattsson, J., Pertesi, M. et al. Genome-wide CRISPR/Cas9 screen identifies regulators of BCMA expression on multiple myeloma cells. Blood Cancer J. 14, 21 (2024). https://doi.org/10.1038/s41408-024-00986-z. January 25, 2024.
Overview
This study focused on finding genes that control BCMA expression. Researchers identified 26 genes, with only four belonging to a process known to influence BCMA. Notably, γ-secretase emerged as a powerful negative regulator of BCMA, a finding supported by a recent clinical trial where patients with relapsed MM received a γ-secretase inhibitor before BCMA CAR T-cell treatment, resulting in a significant increase in BCMA levels.
The research also suggests that impaired N-glycosylation could be a possible resistance mechanism to BCMA-targeted therapies. These genes should be further investigated in samples from MM patients who respond differently to BCMA-targeted treatments, a dataset that may become available as these therapies are used more widely.
Additionally, new genes, like HEXIM1 and UBE2M, were identified that could potentially enhance BCMA expression. While the study didn't delve into the details of each gene, further research is needed to understand their impact on the effectiveness of T-cell immunotherapies for MM, both in laboratory settings and with real patient cells. Overall, the findings offer valuable insights into BCMA regulation, with potential implications for improving multiple myeloma treatment.
"A neutrophil extracellular trap-related risk score predicts prognosis and characterizes the tumor microenvironment in multiple myeloma"
Source
Zhao, Z., Huo, Y., Du, Y. et al. A neutrophil extracellular trap-related risk score predicts prognosis and characterizes the tumor microenvironment in multiple myeloma. Sci Rep 14, 2264 (2024). https://doi.org/10.1038/s41598-024-52922-7. January 27, 2024.
Overview
Multiple myeloma's (MM) connection with neutrophil extracellular traps (NETs) is explored in this study. While previous research hinted at NETs possibly supporting tumor growth in MM, a comprehensive investigation into their role was lacking. Using a dataset, researchers identified active NET cell subgroups, including neutrophils, monocytes, and macrophages. They traced the transcriptional progression of MM and analyzed cellular communication, particularly focusing on neutrophils.
The study revealed increased interactions among cells in MM, although with weakened strength. Abnormal communication links were observed between neutrophils and NK cells in MM samples. By examining differentially expressed genes, a 13-gene risk model for predicting overall survival in MM patients was developed. The high-risk group showed altered immune infiltration and heightened sensitivity to chemotherapy. A survival prediction nomogram demonstrated promising accuracy for 1, 3, and 5-year survival. These findings introduce a novel NET-related prognostic signature for MM, offering a potential avenue for therapeutic exploration.
"ARK5 enhances cell survival associated with mitochondrial morphological dynamics from fusion to fission in human multiple myeloma cells"
Source
Karnan, S., Hanamura, I., Ota, A. et al. ARK5 enhances cell survival associated with mitochondrial morphological dynamics from fusion to fission in human multiple myeloma cells. Cell Death Discov. 10, 56 (2024). https://doi.org/10.1038/s41420-024-01814-w January 29, 2024.
Overview
From the abstract of the study: "5′ adenosine monophosphate–activated protein kinase–related kinase 5 (ARK5) is involved in mitochondrial ATP production and associated with poor prognosis of multiple myeloma (MM). However, the molecular mechanisms of ARK5 in MM remain largely unknown."
This study reveals "that ARK5 expression was closely associated with MAF or MAFB expression and that ARK5 knockout suppressed cell growth and migration in MM. ARK5 expression altered mitochondrial morphology from fusion to fission mediated via increased DRP1S616 phosphorylation, which may have been a good target for treating unfavorable patients with MM expressing ARK5."
"Population pharmacokinetics of lenalidomide in Chinese patients with influence of genetic polymorphisms of ABCB1"
Source
Liang, X., Shi, H., Bi, K. et al. Population pharmacokinetics of lenalidomide in Chinese patients with influence of genetic polymorphisms of ABCB1. Sci Rep 14, 2577 (2024). https://doi.org/10.1038/s41598-024-52460-2. January 31, 2024.
Overview
From the abstract of this study: "Affected by differences in the pharmacokinetics (PK) of lenalidomide, the toxicity of lenalidomide varies among different patients, with serious toxicity leading to dose reduction or discontinuation. The differences in the PK of lenalidomide may be related to factors such as patients’ physiological characteristics, pathological characteristics and gene polymorphisms etc., which may also affect its toxicity. The aim of this study is to establish a population pharmacokinetic (PPK) model of lenalidomide and explore factors associated with the adverse events (AEs) of lenalidomide from a PK perspective. Blood samples were collected by opportunistic blood collection."
The study concluded the following: "The first PPK model of lenalidomide specifically for the Chinese population was established in this study, which indicated that the covariates influencing the V/F of lenalidomide were ABCB1 3435 C > T gene polymorphism and diet. We speculate that patients carrying genotype CC at ABCB1 3435 C > T locus are more likely to be safe to take lenalidomide. However, patients with ABCB1 3435 C > T genotype variant being TT and taking lenalidomide within 1 h after a meal may be prone to serious AEs and need to be further monitored while taking medicine. However, given a relatively small sample size, the present results should be interpreted with caution and investigated further in a larger study population."
"In the era of Bortezomib-based Induction, intensification of Melphalan-based conditioning with Bortezomib does not improve Survival Outcomes in newly diagnosed Multiple Myeloma: a study from the Chronic Malignancies Working Party of the EBMT"
Source
Beksac, M., Eikema, DJ., Koster, L. et al. In the era of Bortezomib-based Induction, intensification of Melphalan-based conditioning with Bortezomib does not improve Survival Outcomes in newly diagnosed Multiple Myeloma: a study from the Chronic Malignancies Working Party of the EBMT. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-023-02160-8. January 31, 2024.
Overview
A study compared two conditioning treatments for autologous hematopoietic stem cell transplantation (AHCT) in multiple myeloma (MM). The treatments were Velcade (Vel) and high-dose Melphalan (Mel200) combination (Vel-Mel) versus Mel200 alone. Researchers analyzed data from MM patients between 2010 and 2017 in 58 centers.
Patients who received Vel-Mel had similar disease characteristics pre-AHCT but were younger and had better overall health. Vel-Mel led to higher rates of complete response (CR) post-induction and by day 100 of AHCT compared to Mel200. However, there was no significant difference in 3-year progression-free survival (PFS) or early post-AHCT mortality. Multivariable analysis revealed that Vel-Mel was associated with inferior PFS and overall survival (OS), similar to negative effects seen with advanced disease stage, high-risk cytogenetics, and poor post-induction response.
Despite superior pre- and post-AHCT responses, Vel-Mel did not improve PFS or OS. This aligns with findings from a smaller prospective study, emphasizing the importance of understanding the overall impact of conditioning treatments in AHCT for multiple myeloma.
"Making decisions for follow-up chemotherapy based on digital patient-reported outcomes data in patients with multiple myeloma and other M protein diseases – A mixed method study."
Source
Rosenberg T, Kirkegaard J, Tveden MG, et al. Making decisions for follow-up chemotherapy based on digital patient-reported outcomes data in patients with multiple myeloma and other M protein diseases – A mixed method study. Eur J Oncol Nurs. 2024;68:102455. doi:10.1016/j.ejon.2023.102455 (February 2024)
Overview
The following are highlights outlined in the abstract of this study:
- "Patient-reported outcomes (PRO) data is useable to decide if patients are physically fit for chemotherapy.
- We developed a questionnaire and a stratifying algorithm with a PPV of 98 %.
- Electronic PRO-guided chemotherapy is suitable for older patients too.
- Self-reporting of side effects made patients feel empowered and independent.
- Healthcare professionals considered the algorithm as a good and valid working tool."