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 February 2025 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 February 2025)
"AAMR-FCN myeloma cancer net: Adaptive and attention-based mask R-FCN for diagnosing myeloma cancer using cell microscopic images with hybrid heuristic strategy, Biomedical Signal Processing and Control"
Source
MM Shinu, D. Pamela, G. Glan Devadhas, J. Samson Isaac, AAMR-FCN myeloma cancer net: Adaptive and attention-based mask R-FCN for diagnosing myeloma cancer using cell microscopic images with hybrid heuristic strategy, Biomedical Signal Processing and Control, Volume 100, Part B, 2025, 106987, ISSN 1746-8094, https://doi.org/10.1016/j.bspc.2024.106987. February 2025.
Overview
Researchers have developed a new AI-powered system to detect multiple myeloma using microscopic blood images. The system, called Adaptive and Attention-based Mask R-FCN (AAMR-FCN), improves the accuracy of identifying cancerous cells by combining two advanced neural networks: R-CNN and FCN.
To further enhance performance, the AI model uses an optimized algorithm (HLO-CSA) that speeds up image analysis and improves detection accuracy. In testing, this model achieved a dice coefficient of 0.998, outperforming existing methods, which scored between 0.984 and 0.989. This means the new system is more precise in identifying multiple myeloma, leading to better diagnosis and patient outcomes.
"MRD-driven phase 2 study of daratumumab, carfilzomib, lenalidomide, and dexamethasone in newly diagnosed multiple myeloma"
Source
Manisha Bhutani, Myra Robinson, David Foureau, Shebli Atrash, Barry Paul, Fei Guo, Jason M. Grayson, Anna Ivanina-Foureau, Mauricio Pineda-Roman, Cindy Varga, Reed Friend, Christopher J. Ferreri, Xhevahire Begic, Sarah Norek, Tiffany Drennan, Michelle B. Anderson, James T. Symanowski, Peter M. Voorhees, Saad Z. Usmani; MRD-driven phase 2 study of daratumumab, carfilzomib, lenalidomide, and dexamethasone in newly diagnosed multiple myeloma. Blood Adv 2025; 9 (3): 507–519. doi: https://doi.org/10.1182/bloodadvances.2024014417 February 11, 2025.
Overview
A new clinical trial tested a personalized treatment approach for newly diagnosed multiple myeloma (NDMM) using a combination of four drugs: daratumumab, carfilzomib, lenalidomide, and dexamethasone (Dara-KRd). Researchers used next-generation sequencing (NGS)-based measurable residual disease (MRD) testing to guide treatment decisions after initial therapy. Among 39 patients, more than half (54%) achieved a complete response after induction therapy. MRD testing showed 59% of patients were MRD-negative at a sensitivity of 10⁻⁵ and 41% at 10⁻⁶, meaning they had very low or undetectable cancer levels.
Based on their MRD status, patients followed different treatment paths. MRD-negative patients continued on lenalidomide maintenance, with 78% remaining MRD-negative for at least a year. MRD-positive, transplant-eligible patients underwent a stem cell transplant, with 62.5% achieving MRD negativity afterward. MRD-positive, transplant-ineligible patients received additional therapy with carfilzomib, lenalidomide, and dexamethasone (KRd). These MRD-adapted strategies helped deepen responses, with overall MRD negativity rates rising to 77% at 10⁻⁵ and 72% at 10⁻⁶ after additional treatment.
Researchers also found that Dara-KRd therapy activated memory T cells, which may have contributed to achieving MRD negativity. With a 30-month follow-up, only six patients had disease progression or died, suggesting the treatment was effective in achieving and maintaining deep responses. Importantly, no new safety concerns were identified. While the trial’s main goal was not fully met, these results highlight how MRD testing can help personalize treatment and improve long-term outcomes for multiple myeloma patients
"Clinical impact of [18F]FDG-PET/CT in ARI0002h treatment, a CAR-T against BCMA for relapsed/refractory multiple myeloma"
Source
Inés Zugasti, Marta Tormo-Ratera, Aina Oliver-Caldés, Juan Carlos Soler-Perromat, Verónica González-Calle, David F. Moreno, Valentín Cabañas, Nieves López-Muñoz, Álvaro Bartolomé-Solanas, Marta Español-Rego, Juan Luis Reguera-Ortega, Laura Rosiñol, Lucía López-Corral, Natalia Tovar, Luis Gerardo Rodríguez-Lobato, Rosa Maria Alvarez Perez, Sara Varea, Eulàlia Olesti, Adolfo Gomez-Grande, Laura Frutos, Pilar Tamayo, Manel Juan, José M. Moraleda, Álvaro Urbano-Ispizua, E. Azucena González-Navarro, Joaquín Martínez-López, Maria-Victoria Mateos, Xavier Tomás, Xavier Setoain, Carlos Fernández de Larrea; Clinical impact of [18F]FDG-PET/CT in ARI0002h treatment, a CAR-T against BCMA for relapsed/refractory multiple myeloma. Blood Adv 2025; 9 (3): 571–582. doi: https://doi.org/10.1182/bloodadvances.2024014360 February 11, 2025.
Overview
CAR T-cell therapy is a promising treatment for relapsed or refractory multiple myeloma (MM), but its effectiveness in patients with soft-tissue plasmacytomas (tumors outside the bone marrow) is not well understood. A recent study examined 63 patients treated with BCMA-targeted CAR T-cell therapy (ARI0002h), either through a clinical trial or compassionate use. Researchers aimed to determine how the presence of extramedullary (EMD) and paraskeletal (PS) plasmacytomas affected treatment response, survival, and safety.
At the start of treatment, 52% of patients had plasmacytomas, with 21 having only PS tumors and 12 having EMD involvement. Overall, response rates were similar between patients with and without plasmacytomas. Additionally, survival outcomes—progression-free survival (PFS) and overall survival (OS)—did not differ significantly, except in patients with EMD, who had a higher risk of disease progression and shorter survival.
Imaging with [18F]FDG-PET/CT scans was useful in predicting outcomes. Patients with higher tumor volume (≥25 cm³) before treatment had earlier disease progression and shorter survival. Additionally, PET/CT scans taken 100 days after CAR T-cell infusion provided valuable insights into patient prognosis. These findings emphasize the importance of early imaging to assess disease severity and predict treatment success in multiple myeloma patients receiving CAR T-cell therapy.
"Pathogenic germ line variants in a prospective multicenter cohort of patients with multiple myeloma"
Source
Julia Erin Wiedmeier-Nutor, Michael A. Golafshar, Katie L. Kunze, Edward D. Esplin, Robert L. Nussbaum, Erik Jessen, Brandie Heald, A. Keith Stewart, N. Jewel Samadder, P. Leif Bergsagel, Rafael Fonseca; Pathogenic germ line variants in a prospective multicenter cohort of patients with multiple myeloma. Blood Neoplasia 2025; 2 (1): 100045. doi: https://doi.org/10.1016/j.bneo.2024.100045 February 19, 2025.
Overview
Researchers are investigating whether inherited genetic mutations (pathogenic germline variants, or PGVs) may play a role in multiple myeloma (MM). While MM is typically driven by acquired (somatic) mutations, identifying inherited risk factors could help with disease monitoring, family risk assessments, and treatment decisions. To explore this, scientists analyzed 74 MM patients at different disease stages using a next-generation sequencing (NGS) panel covering 84 cancer-related genes.
The study found that 6.8% of patients had a PGV, mainly in DNA damage repair genes, including PALB2, TP53, ATM, and CHEK2. These mutations are linked to increased cancer risk and may have clinical implications for cancer screening and family testing. Interestingly, the results aligned with previous research, which reported a similar PGV prevalence (about 9.9%) in larger MM patient groups. However, there was no clear association between PGV status and factors like age, disease stage, or high-risk genetic abnormalities in MM.
While genetic screening can help identify patients at higher risk for other cancers, only one patient’s family chose to participate in genetic testing. This highlights the need for better education on the importance of genetic risk assessment in MM. The researchers emphasize that larger studies are needed to fully understand the role of inherited mutations in MM and how they might impact disease progression, treatment, and cancer prevention strategies for patients and their families.
"Bortezomib enhances the efficacy of BCMA CAR-T therapy through up-regulating BCMA expression in myeloma cells"
Source
Jiaqian Li, Rongbing Guo, Dan Li, Jinrong Yang, Yalan Zhang, Haozhan Gao, Yuening Yang, Fengling Wang, Ting Niu, Wei Wang, Bortezomib enhances the efficacy of BCMA CAR-T therapy through up-regulating BCMA expression in myeloma cells, International Immunopharmacology, Volume 148, 2025, 114113, ISSN 1567-5769, https://doi.org/10.1016/j.intimp.2025.114113. February 20, 2025.
Overview
CAR T-cell therapy targeting B-cell maturation antigen (BCMA) has shown great promise for treating multiple myeloma (MM). Now, researchers have found that bortezomib, a widely used proteasome inhibitor, may help make this therapy even more effective.
The study discovered that bortezomib increases BCMA levels on MM cells, making them more visible to BCMA CAR-T cells. In lab experiments, MM cells treated with low doses of bortezomib had higher BCMA expression and were more vulnerable to CAR-T cell attack. This effect was confirmed in animal studies, where the combination of bortezomib and BCMA CAR-T therapy improved tumor control and increased survival rates.
Importantly, safety tests showed that the combination treatment was well tolerated, with no significant tissue damage or weight loss observed. These findings suggest that using bortezomib alongside BCMA CAR-T therapy could be a safe and effective strategy to enhance treatment outcomes for multiple myeloma patients.
"Targeting BCMA in multiple myeloma: designs, challenges, and future directions"
Source
Hu, Y., Xie, Y., Wang, X. et al. Targeting BCMA in multiple myeloma: designs, challenges, and future directions. Cancer Immunol Immunother 74, 77 (2025). https://doi.org/10.1007/s00262-024-03913-0 February 1, 2025.
Overview
CAR T-cell therapy is a powerful new treatment for B-cell cancers, including multiple myeloma (MM). One key target for this therapy is B-cell maturation antigen (BCMA), a protein found on myeloma cells. This has led to the development of BCMA-targeting CAR T-cell therapies, two of which have already been FDA-approved for MM.
This review explores how BCMA CAR T cells are designed and their impact on patient outcomes. It also examines key challenges, including antigen escape, where myeloma cells lose BCMA to evade treatment, and side effects linked to CAR T therapy.
Looking ahead, researchers are working on next-generation CAR T strategies, such as dual-targeting CAR T cells, improved manufacturing processes, and allogeneic (off-the-shelf) CAR T cells from healthy donors. These innovations could make CAR T-cell therapy more effective and accessible, offering new hope for patients with multiple myeloma and other blood cancers.
"Efficacy and Prognostic Indicators of Isatuximab, Pomalidomide, and Dexamethasone (IsaPd) in Daratumumab-Refractory Multiple Myeloma Patients: A Multicenter Real-World Study"
Source
Martino, E.A., Derudas, D., Rossi, E., Stefanoni, P., Mangiacavalli, S., Zamagni, E., Offidani, M., Furlan, A., Quinto, A.M., Della Pepa, R., Bertuglia, G., Barbieri, E., Conticello, C., De Magistris, C., Bongarzoni, V., Cafro, A.M., Mele, A., Botta, C., Sgherza, N., Mele, G., Annibali, O., Rago, A., Fontana, R., Vigna, E., Bruzzese, A., Mancuso, K., Amendola, A., Citro, A., Cotzia, E., Morè, S., Rivolti, E., Pettine, L., Galli, M., De Stefano, V., Petrucci, M.T., Corso, A., Neri, A., Di Raimondo, F., Bolli, N., Musto, P., Morabito, F. and Gentile, M. (2025), Efficacy and Prognostic Indicators of Isatuximab, Pomalidomide, and Dexamethasone (IsaPd) in Daratumumab-Refractory Multiple Myeloma Patients: A Multicenter Real-World Study. Hematological Oncology, 43: e70042. https://doi.org/10.1002/hon.70042 February 3, 2025.
Overview
A real-world study evaluated the effectiveness of isatuximab, pomalidomide, and dexamethasone (IsaPd) in 51 multiple myeloma (MM) patients who no longer responded to daratumumab (Dara-R). Many participants were heavily pretreated, with 74.5% resistant to three major drug classes. The study found that 57% of patients responded to IsaPd, with some achieving complete remission or a very good partial response. Notably, age, prior treatments, and time since developing daratumumab resistance did not affect response rates.
Despite promising response rates, progression-free survival (PFS) remained modest at 5.8 months, with only 30.6% of patients progression-free at 12 months. Low hemoglobin levels (<11.8 g/L) were a strong predictor of shorter PFS, increasing the risk of disease progression by 3.5 times. Similarly, overall survival (OS) was 21 months, but patients with hemoglobin levels below 11 g/L faced a tenfold higher risk of death. Among patients who underwent cytogenetic testing, high-risk abnormalities significantly increased the likelihood of disease progression, though they did not appear to impact overall survival.
These findings suggest that IsaPd is a meaningful option for MM patients resistant to daratumumab, but the relatively short PFS highlights the need for improved treatment strategies. Hemoglobin levels emerged as a key predictor of both PFS and OS, which may help guide treatment decisions. Future studies should explore new drug combinations to enhance long-term outcomes for these high-risk patients.
"Efficacy and Prognostic Indicators of Isatuximab, Pomalidomide, and Dexamethasone (IsaPd) in Daratumumab-Refractory Multiple Myeloma Patients: A Multicenter Real-World Study"
Source
Martino, E.A., Derudas, D., Rossi, E., Stefanoni, P., Mangiacavalli, S., Zamagni, E., Offidani, M., Furlan, A., Quinto, A.M., Della Pepa, R., Bertuglia, G., Barbieri, E., Conticello, C., De Magistris, C., Bongarzoni, V., Cafro, A.M., Mele, A., Botta, C., Sgherza, N., Mele, G., Annibali, O., Rago, A., Fontana, R., Vigna, E., Bruzzese, A., Mancuso, K., Amendola, A., Citro, A., Cotzia, E., Morè, S., Rivolti, E., Pettine, L., Galli, M., De Stefano, V., Petrucci, M.T., Corso, A., Neri, A., Di Raimondo, F., Bolli, N., Musto, P., Morabito, F. and Gentile, M. (2025), Efficacy and Prognostic Indicators of Isatuximab, Pomalidomide, and Dexamethasone (IsaPd) in Daratumumab-Refractory Multiple Myeloma Patients: A Multicenter Real-World Study. Hematological Oncology, 43: e70042. https://doi.org/10.1002/hon.70042 February 3, 2025.
Overview
A real-world study evaluated the effectiveness of isatuximab, pomalidomide, and dexamethasone (IsaPd) in 51 multiple myeloma (MM) patients who no longer responded to daratumumab (Dara-R). Many participants were heavily pretreated, with 74.5% resistant to three major drug classes. The study found that 57% of patients responded to IsaPd, with some achieving complete remission or a very good partial response. Notably, age, prior treatments, and time since developing daratumumab resistance did not affect response rates.
Despite promising response rates, progression-free survival (PFS) remained modest at 5.8 months, with only 30.6% of patients progression-free at 12 months. Low hemoglobin levels (<11.8 g/L) were a strong predictor of shorter PFS, increasing the risk of disease progression by 3.5 times. Similarly, overall survival (OS) was 21 months, but patients with hemoglobin levels below 11 g/L faced a tenfold higher risk of death. Among patients who underwent cytogenetic testing, high-risk abnormalities significantly increased the likelihood of disease progression, though they did not appear to impact overall survival.
These findings suggest that IsaPd is a meaningful option for MM patients resistant to daratumumab, but the relatively short PFS highlights the need for improved treatment strategies. Hemoglobin levels emerged as a key predictor of both PFS and OS, which may help guide treatment decisions. Future studies should explore new drug combinations to enhance long-term outcomes for these high-risk patients.
"Isatuximab, bortezomib, lenalidomide, and limited dexamethasone in patients with transplant-ineligible multiple myeloma (REST): a multicentre, single-arm, phase 2 trial"
Source
Askeland, Frida Bugge et al. Isatuximab, bortezomib, lenalidomide, and limited dexamethasone in patients with transplant-ineligible multiple myeloma (REST): a multicentre, single-arm, phase 2 trial. The Lancet Haematology, Volume 12, Issue 2, e120 - e127. February 2025.
Overview
A recent study focused on creating guidelines for managing multiple myeloma (MM), a type of cancer that affects plasma cells in the bone marrow. The research aimed to provide evidence-based recommendations for diagnosis, prognosis, and treatment of MM, using insights from a comprehensive literature review and meta-analysis. The team identified 12 key clinical questions that guide MM care, with recommendations tailored to integrate both patient preferences and survey data.
The guidelines highlight current and emerging diagnostic tools, as well as therapeutic agents and treatment strategies. By focusing on patient-centered care and rigorous data analysis, these guidelines aim to improve the management of MM, both in Korea and globally, ensuring that patients receive the most effective, evidence-supported care.
"Clinicopathologic predictors of renal response and survival in newly diagnosed multiple myeloma with renal injury: a retrospective study"
Source
Wei, W., Shi, H., Chen, H. et al. Clinicopathologic predictors of renal response and survival in newly diagnosed multiple myeloma with renal injury: a retrospective study. Clin Exp Med 25, 48 (2025). https://doi.org/10.1007/s10238-025-01571-9 February 4, 2025.
Overview
A recent study focused on creating guidelines for managing multiple myeloma (MM), a type of cancer that affects plasma cells in the bone marrow. The research aimed to provide evidence-based recommendations for diagnosis, prognosis, and treatment of MM, using insights from a comprehensive literature review and meta-analysis. The team identified 12 key clinical questions that guide MM care, with recommendations tailored to integrate both patient preferences and survey data.
The guidelines highlight current and emerging diagnostic tools, as well as therapeutic agents and treatment strategies. By focusing on patient-centered care and rigorous data analysis, these guidelines aim to improve the management of MM, both in Korea and globally, ensuring that patients receive the most effective, evidence-supported care.
"Genetic disruption of Blimp-1 drastically augments the antitumor efficacy of BCMA-targeting CAR T cells"
Source
Anthony M. Battram, Joan Mañé-Pujol, David F. Moreno, Aina Oliver-Caldés, Judit Carpio, Oriol Cardus, Luis Gerardo Rodríguez-Lobato, Álvaro Urbano-Ispizua, Carlos Fernández de Larrea; Genetic disruption of Blimp-1 drastically augments the antitumor efficacy of BCMA-targeting CAR T cells. Blood Adv 2025; 9 (3): 627–641. doi: https://doi.org/10.1182/bloodadvances.2024013209 February 11, 2025.
Overview
CAR T-cell therapy targeting B-cell maturation antigen (BCMA) is an effective treatment for multiple myeloma (MM), but its short-term effectiveness and relapses remain a challenge. The issue stems from premature differentiation of CAR T cells, which limits the formation of long-lasting memory cells that could maintain antitumor responses. To improve the durability of this treatment, researchers used CRISPR gene editing to remove Blimp-1, a transcription factor. This created CAR T cells with a memory-like phenotype, which performed better in a murine model of MM, significantly improving survival compared to untreated cells.
Although the Blimp-1 knockout (KO) CAR T cells had lower effector functions, including reduced granzyme B activity, they showed enhanced effectiveness when repeatedly exposed to tumor cells. These Blimp-1 KO CAR T cells maintained a high activity level and exhibited memory markers while demonstrating improved effector function and increased energy. RNA sequencing revealed a memory-like gene signature and enhanced ribosome activity, which might explain their improved antitumor response. This study suggests that modifying Blimp-1 expression can enhance the performance of anti-BCMA CAR T cells, offering a potential approach to improve long-term treatment efficacy for multiple myeloma.
"Phase 1 clinical trial of B-Cell Maturation Antigen (BCMA) NEX-T® Chimeric Antigen Receptor (CAR) T cell therapy CC-98633/BMS-986354 in participants with triple-class exposed multiple myeloma"
Source
Ravi, G., Richard, S., Kumar, S. et al. Phase 1 clinical trial of B-Cell Maturation Antigen (BCMA) NEX-T® Chimeric Antigen Receptor (CAR) T cell therapy CC-98633/BMS-986354 in participants with triple-class exposed multiple myeloma. Leukemia (2025). https://doi.org/10.1038/s41375-025-02518-5 February 5, 2025
Overview
BCMA-targeted CAR T-cell therapy has significantly advanced the treatment of relapsed and refractory multiple myeloma (RRMM), but improvements are still needed in manufacturing, toxicity, and effectiveness. A phase 1 clinical trial tested BMS-986354, an autologous BCMA CAR T-cell therapy manufactured using an optimized process called NEX-T®, in 65 participants with heavily pretreated RRMM. Most participants had a median of 5 prior treatments, with 39% having high-risk cytogenetic abnormalities and 91% being refractory to triple-class therapies.
The study included a dose-escalation phase (Part A), with doses of 20, 40, or 80 million CAR T-cells, and an expansion phase (Part B) at a recommended dose of 40 million CAR T-cells. The results showed 95% response rate, with 46% of patients achieving a complete response. However, side effects like cytokine release syndrome (CRS) (82%, 2% severe), neurotoxicity (8%, 2% severe), and infections (32%, 5% severe) were observed. The median progression-free survival (PFS) was 12.3 months. Compared to other therapies using the same CAR construct, BMS-986354 showed higher T central memory cells, better potency, and improved ability to proliferate, indicating that NEX-T® may be a promising approach for future CAR T-cell treatments.
"Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS study"
Source
Usmani, S.Z., Facon, T., Hungria, V. et al. Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS study. Nat Med (2025). https://doi.org/10.1038/s41591-024-03485-7 February 5, 2025.
Overview
A phase 3 trial tested a combination of daratumumab with bortezomib, lenalidomide, and dexamethasone (D-VRd) in patients with newly diagnosed multiple myeloma (NDMM) who were either transplant-ineligible or had deferred transplant. The study compared this combination to the standard treatment, VRd (bortezomib, lenalidomide, and dexamethasone alone), in 395 patients. The goal was to see how well the combination reduced minimal residual disease (MRD), a sign of remaining cancer after treatment.
Results showed that the D-VRd combination had a 60.9% MRD-negativity rate, significantly higher than the 39.4% for VRd alone. Additionally, D-VRd led to higher complete response (CR) rates (81.2% vs. 61.6%), and patients on D-VRd had a 43% lower risk of progression or death compared to those on VRd alone. The study found that D-VRd provided deeper and longer-lasting MRD responses, making it a promising new standard of care for transplant-ineligible or transplant-deferred NDMM patients. The safety profile was consistent with known side effects of daratumumab and VRd.
"Exploring BCL2 regulation and upstream signaling transduction in venetoclax resistance in multiple myeloma: potential avenues for therapeutic intervention"
Source
Fonseca, R., Zhu, Y.X., Bruins, L.A. et al. Exploring BCL2 regulation and upstream signaling transduction in venetoclax resistance in multiple myeloma: potential avenues for therapeutic intervention. Blood Cancer J. 15, 10 (2025). https://doi.org/10.1038/s41408-025-01215-x February 5, 2025.
Overview
Researchers studied why venetoclax (VTX), a drug used to treat multiple myeloma (MM), doesn't always work in some patients. They looked at human myeloma cell lines and MM patient samples both before and after VTX treatment to understand what causes resistance. Their analysis found that resistance was mainly linked to changes in the BCL-2 family of proteins, which help control cell survival. Specifically, anti-apoptotic proteins like MCL-1, BCL-XL, and BCL-2 were overactive, while pro-apoptotic proteins were less active.
The study showed that reintroducing BIM, a protein that promotes cell death, helped restore the cells' sensitivity to VTX. Combining VTX with MCL-1 inhibitors was especially effective. The researchers also found that certain signaling pathways, like RTK (growth factor receptors) and PI3K, contributed to this resistance. Blocking these pathways, along with MCL-1 and BCL-XL inhibitors, made the resistant cells more responsive to VTX. Other factors, like modifications to MCL-1 and mitochondrial function, had a smaller effect. The study suggests that combining VTX with specific inhibitors could be a potential strategy for overcoming resistance and improving treatment outcomes for MM patients.
"Real-world outcomes of maintenance therapy post-autologous stem cell transplantation in newly diagnosed multiple myeloma"
Source
Kang, KW., Kim, D.S., Lee, S.R. et al. Real-world outcomes of maintenance therapy post-autologous stem cell transplantation in newly diagnosed multiple myeloma. BMC Cancer 25, 204 (2025). https://doi.org/10.1186/s12885-025-13518-0 February 5, 2025.
Overview
A study in South Korea looked at whether maintenance therapy improves survival for people with newly diagnosed multiple myeloma (MM) after undergoing autologous stem cell transplantation (ASCT). Researchers compared the outcomes of 512 patients who received either maintenance therapy or no maintenance therapy after treatment with a combination of bortezomib, thalidomide, and dexamethasone. Of the 153 patients who received maintenance therapy, most were treated with thalidomide (68%), followed by lenalidomide (21%) and bortezomib or ixazomib (10%).
The study found that patients who received maintenance therapy had a longer progression-free survival (PFS) — an average of 44.1 months compared to 26.4 months in the no-maintenance group. The analysis also showed that using bortezomib or ixazomib was linked to better PFS compared to other drugs, and longer therapy duration further improved PFS. However, there were no significant differences in overall survival or the risk of developing secondary cancers based on the type of maintenance therapy.
Overall, the study suggests that while maintenance therapy after ASCT may lead to longer periods without disease progression, it does not appear to significantly increase the risk of secondary cancers, supporting its use as part of MM treatment.
"Implications of isolated MRD progression in newly diagnosed multiple myeloma treated with quadruplet therapy"
Source
Costa, L.J., Medvedova, E., Dhakal, B. et al. Implications of isolated MRD progression in newly diagnosed multiple myeloma treated with quadruplet therapy. Blood Cancer J. 15, 13 (2025). https://doi.org/10.1038/s41408-025-01219-7 February 5, 2025.
Overview
In multiple myeloma (MM), monitoring disease progression and response to treatment is crucial. Traditionally, serum and urine paraprotein levels are used to track the disease. However, as treatments improve, measurable residual disease (MRD) monitoring has become more important. This study focused on MRD rise as an indicator of disease progression, even when traditional biomarkers like paraprotein do not show a rise. The research used data from the MASTER trial and additional patients treated with daratumumab-based therapies to examine the impact of MRD rise without other signs of progression.
The study found that a rise in MRD was linked to a similar risk of disease progression as an increase in paraprotein levels, suggesting that MRD monitoring could be just as effective in predicting disease relapse. For many patients, the rise in MRD occurred before any noticeable symptoms or increase in paraprotein. When MRD rose, doctors typically adjusted treatment to address the increasing cancer load. The results suggest that MRD rise is an important marker of disease activity and should be closely watched, especially in patients treated with quadruplet therapy and autologous stem cell transplantation (ASCT).
This research calls for a shift in how disease progression is defined and managed in MM, particularly with newer therapies. The study shows that MRD rise, even without the typical signs of progression, can be a warning sign that the cancer may become more resistant to treatment. Further studies are needed to confirm these findings and refine how MRD progression should be treated in clinical practice.
"Is t(11;14) in newly diagnosed multiple myeloma a favorable outcome in the novel agent era?"
Source
Li, Y., Deng, J., Jian, Y. et al. Is t(11;14) in newly diagnosed multiple myeloma a favorable outcome in the novel agent era?. Blood Res. 60, 11 (2025). https://doi.org/10.1007/s44313-025-00056-8 February 6, 2025.
Overview
In multiple myeloma (MM), a specific genetic marker, t(11;14), has been thought to indicate standard risk. However, newer treatments have raised questions about its true impact. This study looked at the outcomes of 375 newly diagnosed MM patients, comparing those with t(11;14) to those with normal genetics.
The results showed that patients with t(11;14) had a shorter progression-free survival (PFS) (36 months) compared to patients with normal cytogenetics (65 months). However, overall survival (OS) was similar between the two groups. When t(11;14) was combined with 1q21+, it appeared to worsen PFS. Also, in patients with high-risk genetic features, t(11;14) led to a worse PFS and potentially shorter OS.
The study suggests that t(11;14) could be a negative factor for prognosis, but autologous stem cell transplantation (ASCT) might improve outcomes for these patients. More research is needed to fully understand how t(11;14) affects treatment responses with newer therapies.
"Metabolomics approach reveals key plasma biomarkers in multiple myeloma for diagnosis, staging, and prognosis"
Source
Wang, X., Cheng, L., Liu, A. et al. Metabolomics approach reveals key plasma biomarkers in multiple myeloma for diagnosis, staging, and prognosis. J Transl Med 23, 163 (2025). https://doi.org/10.1186/s12967-024-05848-7 February 6, 2025.
Overview
In this study, researchers wanted to understand the metabolic changes in multiple myeloma (MM) and find potential new targets for treatment. They analyzed plasma samples from 38 newly diagnosed MM patients, 92 patients who had received treatment, and 33 healthy controls.
Using advanced techniques, the study identified 70 metabolites that were altered in MM patients. These metabolites were linked to important processes like energy production and fat metabolism. Notably, levels of lactic acid and leucine were identified as potential biomarkers, which could help in diagnosing MM, tracking its stage, and predicting patient outcomes. Some of these findings were confirmed in laboratory tests using MM cell lines, showing that lactate and leucine levels were lower in the cells.
The study highlights key metabolites that could lead to new ways of diagnosing and treating MM. Further research is needed to confirm these findings and improve care for MM patients in the future.
"Huachansu Injection induces ferroptosis in multiple myeloma through NRF2/HO-1 signaling pathway"
Source
Jing Yang, Fengnan Wang, Zhongxiao Hu, Xixi Liu, Weiguang Zhang, Chencheng Li, Wanxia Wang, Jianati Reaila, Xiaoli Zhang, Guangrong Zhu, Fang Tian, Biqing Chen, Xuejue Zhu, Huachansu Injection induces ferroptosis in multiple myeloma through NRF2/HO-1 signaling pathway, Journal of Ethnopharmacology, 2025, 119454, ISSN 0378-8741, https://doi.org/10.1016/j.jep.2025.119454. February 6, 2025.
Overview
Huachansu (HCS), a substance derived from the skin of the Bufo bufo gargarizans frog, has shown anti-tumor effects and potential in treating multiple myeloma (MM), but how it works is not fully understood.
This study aimed to investigate how HCS kills MM cells at the cellular and molecular levels. Researchers tested HCS on MM cells and used various techniques to measure changes in cell viability, gene expression, and markers of cell death. They also tested HCS in mice with MM to observe its effects in a living organism.
The study found that HCS triggers a type of cell death called ferroptosis by activating a specific pathway (NRF2/HO-1). This pathway led to an increase in iron and reactive oxygen species (ROS), which are harmful to cells, and a decrease in antioxidants. Ferroptosis inhibitors could reverse these effects, suggesting that HCS’s impact on MM cells is through ferroptosis. In mice, HCS was effective in slowing MM progression, similar to a standard treatment drug called bortezomib.
The study suggests that HCS could be used as a natural treatment for MM by inducing ferroptosis, and it may also work well with traditional chemotherapy drugs for a combined treatment approach.
"Targeting Caseinolytic Mitochondrial Matrix Peptidase, a Novel Contributor to High-risk Behavior, in Multiple Myeloma"
Source
Li Qin, Luz Yurany Moreno Rueda, Upasana Ray, Iqbal Mahmud, Lin Tan, Philip L Lorenzi, Suyu Liu, Heather Yan Lin, David E. Mery, Fenghuang Zhan, John D. Shaughnessy, Qing Yi, Maria Jose Acevedo Calado, Hua Wang, Elisabet E. Manasanch, Hans C. Lee, Krina K. Patel, Isere Kuiatse, David E. Symer, Robert Z. Orlowski; Targeting Caseinolytic Mitochondrial Matrix Peptidase, a Novel Contributor to High-risk Behavior, in Multiple Myeloma. Blood 2025; blood.2024024781. doi: https://doi.org/10.1182/blood.2024024781 February 6, 2025.
Overview
Plasma cell dyscrasias, which include conditions like monoclonal gammopathy of undetermined significance, smoldering myeloma, and symptomatic myeloma, are not fully understood in terms of the genes that contribute to their progression and poor prognosis. In this study, researchers used advanced single-cell techniques to identify a protein called CLPP, which is overactive in cancerous plasma cells compared to normal ones. High levels of CLPP are linked to a worse outlook for patients, including those with relapsed or advanced myeloma.
The study found that blocking or reducing CLPP activity slowed the growth of myeloma cells, caused cell death, and disrupted cell processes like energy production and protein folding. This also helped overcome resistance to other treatments, showing promise for combining CLPP inhibitors with current therapies like proteasome inhibitors, drugs targeting metabolism, and autophagy inhibitors.
In summary, CLPP plays a key role in myeloma progression and resistance to treatment, making it a valuable target for new treatments. Using drugs like inobrodib, which inhibit CLPP, could improve outcomes for myeloma patients when combined with existing therapies.
"Bortezomib, thalidomide, and dexamethasone versus bortezomib, lenalidomide, and dexamethasone in transplant-eligible newly diagnosed multiple myeloma: a systemic review and meta-analysis"
Source
Wang, Y. C., Lin, C. H., Su, Y. C., & Teng, C. L. J. (2025). Bortezomib, thalidomide, and dexamethasone versus bortezomib, lenalidomide, and dexamethasone in transplant-eligible newly diagnosed multiple myeloma: a systemic review and meta-analysis. Hematology, 30(1). https://doi.org/10.1080/16078454.2025.2462249 February 6, 2025.
Overview
This study compared two treatment regimens, VTdand VRd, in patients with newly diagnosed multiple myeloma (NDMM) who are eligible for a stem cell transplant. The goal was to assess how well each treatment worked, the need for a stem cell transplant, and the occurrence of serious side effects.
The review included 15 studies: six on the VTd regimen and nine on the VRdregimen. Both groups showed similar response rates, with the VTD group having a 93% overall response rate (ORR) and the VRd group having an 86% ORR. Both treatments had similar rates of very good partial response (VGPR), around 60%. The VTd group had a higher rate of needing a stem cell transplant (93%) compared to the VRD group (70%).
In terms of side effects, both groups had similar rates of serious side effects like blood-related problems (around 31-33%), infections (9% for VTD and 14% for VRD), and blood clots (4% for VTd and 3% for VRd).
Overall, both VTD and VRD were similarly effective and had comparable safety profiles for patients with transplant-eligible NDMM.
"Myeloma cell-derived CXCL7 facilitates proliferation of tumor cells and occurrence of osteolytic lesions through JAK/STAT3 pathway"
Source
Wang, Y., Lan, T., Zhang, Q. et al. Myeloma cell-derived CXCL7 facilitates proliferation of tumor cells and occurrence of osteolytic lesions through JAK/STAT3 pathway. Cell Death Dis 16, 74 (2025). https://doi.org/10.1038/s41419-025-07413-6 February 6, 2025.
Overview
Researchers have identified a subset of multiple myeloma (MM) cells with high levels of CXCL7, a protein that may play a key role in bone damage. These cells grow rapidly and activate osteoclasts, the cells that break down bone, increasing the risk of osteolytic lesions and fractures. In both lab studies and a mouse model, high CXCL7 levels led to faster MM cell growth, bone loss, and femur fractures. CXCL7 appears to trigger the JAK/STAT3 pathway and increase levels of MMP13 and C-myc, which further promote bone damage and cancer progression. These findings suggest that targeting CXCL7 could be a potential new treatment strategy for MM.
"Bone marrow breakout lesions act as key sites for tumor-immune cell diversification in multiple myeloma"
Source
Raphael Lutz et al., Bone marrow breakout lesions act as key sites for tumor-immune cell diversification in multiple myeloma. Sci. Immunol.10, eadp6667(2025). DOI:10.1126/sciimmunol.adp6667 February 7, 2025.
Overview
As multiple myeloma progresses, cancer cells can evolve to survive outside the bone marrow, but the process behind this shift is not well understood. Researchers used single-cell and spatial multiomics analysis to compare myeloma confined to the bone marrow with breakout lesions, which break through the bone. These lesions had a unique cellular environment, with clusters of immune cells, natural killer cells, and macrophages among malignant plasma cells. In these clusters, T cells expanded alongside genetic changes in tumor cells, highlighting breakout lesions as key sites where myeloma adapts and interacts with the immune system. Understanding this process may help develop better treatments.
"The clinical journey of belantamab mafodotin in relapsed or refractory multiple myeloma: lessons in drug development"
Source
Mukhopadhyay, P., Abdullah, H.A., Opalinska, J.B. et al. The clinical journey of belantamab mafodotin in relapsed or refractory multiple myeloma: lessons in drug development. Blood Cancer J. 15, 15 (2025). https://doi.org/10.1038/s41408-025-01212-0 February 7, 2025.
Overview
Patients with relapsed or refractory multiple myeloma (RRMM) need better treatment options. Belantamab mafodotin, a drug targeting B-cell maturation antigen (BCMA), was initially approved based on promising response rates. However, despite showing durable responses in a phase III trial (DREAMM-3), it was withdrawn from US and European markets because it did not outperform standard treatment in progression-free survival. Researchers suggest that longer follow-up and different trial designs may have better captured its benefits. Ongoing DREAMM-7 and DREAMM-8 trials are now testing belantamab mafodotin in combination therapies to improve its effectiveness and ensure better outcomes for RRMM patients.
"Single-cell sequencing reveals the mechanisms of multiple myeloma progression: clarity or confusion?"
Source
Xiang, Y., Sun, G., Tian, L. et al. Single-cell sequencing reveals the mechanisms of multiple myeloma progression: clarity or confusion?. Ann Hematol (2025). https://doi.org/10.1007/s00277-025-06241-0 February 7, 2025.
Overview
The combination of Sarclisa® (isatuximab) with Velcade® (bortezomib), Revlimid® (lenalidomide) and dexamethasone, or VRd, has shown positive results for people with newly diagnosed multiple myeloma (NDMM) who are not candidates for a transplant. In a phase III study, the addition of isatuximab improved progression-free survival (PFS), with a 5-year PFS rate of 63.2% compared to 45.2% for VRd alone. The combination also led to better minimal residual disease (MRD) status and response rates. However, overall survival data is still pending. While more adverse events were reported in the Isa-VRd group, the treatment showed clear benefits for people with NDMM.
"Cumulative Excess Body Mass Index and MGUS Progression to Myeloma"
Source
Liu L, Grandhi N, Wang M, et al. Cumulative Excess Body Mass Index and MGUS Progression to Myeloma. JAMA Netw Open. 2025;8(2):e2458585. doi:10.1001/jamanetworkopen.2024.58585 February 7, 2025.
Overview
Obesity is linked to a higher risk of developing multiple myeloma (MM) and its precursor, monoclonal gammopathy of unknown significance (MGUS). This study looked at how long-term obesity affects the progression from MGUS to MM. Researchers found that for patients with a healthy BMI (18.5 to less than 25) at the time of MGUS diagnosis, gaining excess weight (BMI of 25 or higher) increased the risk of developing MM. However, once patients already had a BMI of 25 or higher, the effect of weight gain was less clear. These findings suggest that keeping a healthy weight after a MGUS diagnosis may help prevent the disease from progressing to MM.
"Oral Plasmacytoma in Multiple Myeloma Patients: report of 18 cases"
Source
Lama Alabdulaaly, Maryam Jessri, Nathaniel Treister, Tiffany Tavares, Efstathios Pettas, Sook-Bin Woo, Jacob Laubach, Alessandro Villa, Oral Plasmacytoma in Multiple Myeloma Patients: report of 18 cases, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 2025, ISSN 2212-4403, https://doi.org/10.1016/j.oooo.2025.02.002. February 8, 2025.
Overview
Oral plasmacytoma is a rare condition that can occur in multiple myeloma (MM) patients, affecting the oral mucosa and jaw bones. In a study of 18 MM patients, most of them experienced symptoms like pain and bleeding, with the gingiva (gums) being the most common site affected. Gnathic (jaw) involvement was seen in some cases, while others had soft tissue disease without bone involvement. Despite treatment for the oral disease, most patients passed away within 5 months. This highlights the need for early recognition and management of oral plasmacytomas in MM patients.
"Second-line anti-CD38 monoclonal antibody therapy mitigates the negative impact of functional high-risk status in myeloma patients"
Source
Suzuki, K., Gunji, T., Nagao, R. et al. Second-line anti-CD38 monoclonal antibody therapy mitigates the negative impact of functional high-risk status in myeloma patients. Int J Hematol (2025). https://doi.org/10.1007/s12185-025-03941-1 February 9, 2025.
Overview
In multiple myeloma, patients with functional high risk (FHR) typically have worse outcomes. FHR is defined by a reduced M protein level or early disease progression within 12 months. This study looked at the use of anti-CD38 monoclonal antibodies (MoAb) as a second-line treatment for FHR myeloma. The study included 332 patients, with 29.4% being FHR. Results showed that overall survival (OS) was shorter for FHR patients, but those who received anti-CD38 MoAb treatment had outcomes similar to patients without FHR. This suggests that anti-CD38 MoAb could improve outcomes for FHR patients despite their initial poor prognosis.
"Prevalence and Survival Impact of Venous and Arterial Thrombosis among Multiple Myeloma Patients in Single Tertiary Care Center of Thailand: 5-Year Retrospective Review"
Source
Hongtongsagool, P., Teawtrakul, N., Wanitpongpun, C. et al. Prevalence and Survival Impact of Venous and Arterial Thrombosis among Multiple Myeloma Patients in Single Tertiary Care Center of Thailand: 5-Year Retrospective Review. Indian J Hematol Blood Transfus (2025). https://doi.org/10.1007/s12288-024-01938-0 February 11, 2025.
Overview
In Thai patients with multiple myeloma in this study, thrombosis (blood clots) occurs at relatively low rates, with venous thromboembolism affecting 8.22% and arterial thrombosis affecting 1.37%. The study found no significant difference in overall survival between patients with and without thrombosis, as survival rates were similar for both groups. The use of thromboprophylaxis (blood-thinning treatment) was linked to a lower risk of thrombosis without increasing the risk of bleeding. Overall, while thrombosis is uncommon in these patients, thromboprophylaxis may be beneficial in reducing clot risks.
"NK Cell Immaturity and NKp30 Expression Positively Correlate with Clinical Outcome in Multiple Myeloma Patients from the IFM2009 Clinical Trial"
Source
Villard, M., Viel, S., Karlin, L., Avet-Loiseau, H., Martinet, L., Marçais, A. and Walzer, T. (2025), NK Cell Immaturity and NKp30 Expression Positively Correlate with Clinical Outcome in Multiple Myeloma Patients from the IFM2009 Clinical Trial. Eur. J. Immunol., 55: e202451191. https://doi.org/10.1002/eji.202451191 February 11, 2025.
Overview
In multiple myeloma (MM), natural killer (NK) cells, which can attack MM cells, show altered behavior. In this study, NK cells in the bone marrow of MM patients were analyzed, revealing that although NK cells were more frequent, they had signs of immaturity. These NK cells also had changes in certain markers, with more immature and resident NK cells present in patients with advanced stages of the disease. Interestingly, a better clinical outcome was linked to immature NK cells, especially those with higher levels of the NKp30 receptor. This suggests that these immature NK cells might play a key role in fighting MM, offering a potential target for new treatments.
"Construction of tetravalent bispecific Tandab (CD3/BCMA)-secreting human umbilical cord mesenchymal stem cells and its efficiency in the treatment of multiple myeloma"
Source
Xiong, M., Kong, C., Lu, Y. et al. Construction of tetravalent bispecific Tandab (CD3/BCMA)-secreting human umbilical cord mesenchymal stem cells and its efficiency in the treatment of multiple myeloma. Stem Cell Res Ther 16, 69 (2025). https://doi.org/10.1186/s13287-025-04212-w February 12, 2025.
Overview
Researchers are exploring new therapies for multiple myeloma (MM), a cancer that urgently needs more targeted treatments. In this study, mesenchymal stem cells (MSCs) were engineered to produce a Tandab (CD3/BCMA), a dual-target antibody designed to treat MM. MSCs are promising because they naturally move toward tumors. The engineered MSCs were able to target BCMA-positive MM cells and activate human T cells to attack the cancer cells without affecting healthy cells. When tested in a mouse model, MSCs secreting Tandab significantly reduced the tumor size and boosted immune activity without causing side effects. This shows that MSC-based therapies could be a new way to treat MM.
"Current State of Evidence on Definitions and Management of High-Risk Multiple Myeloma"
Source
Mohan Lal, B., van Rhee, F. & Al Hadidi, S. Current State of Evidence on Definitions and Management of High-Risk Multiple Myeloma. Curr Oncol Rep (2025). https://doi.org/10.1007/s11912-025-01639-5 February 12, 2025.
Overview
This review focuses on high-risk multiple myeloma (HRMM) patients who still have poor outcomes despite recent treatment advances. It highlights the challenges in defining HRMM, as no universally accepted definition exists. Researchers are exploring various factors, such as clinical, genetic, and imaging data, to better identify these patients. While HRMM patients show varied responses to treatment, there is growing support for developing more targeted strategies to improve outcomes. The review stresses the need for a consistent definition of HRMM and emphasizes the importance of clinical trials to address gaps in treatment for this high-risk group.
"Exploring the impact of Dysgeusia on Sensory Perception, Appetite, and Texture During Oral Nutritional Supplement Consumption in Head and Neck Cancer and Multiple Myeloma Patients"
Source
Ghias Kulsoom, Krawczyk Janusz, Gupta Ananya, Exploring the impact of Dysgeusia on Sensory Perception, Appetite, and Texture During Oral Nutritional Supplement Consumption in Head and Neck Cancer and Multiple Myeloma Patients, Clinical Nutrition Open Science, 2025, ISSN 2667-2685, https://doi.org/10.1016/j.nutos.2025.01.008. February 12, 2025.
Overview
This study explores how dysgeusia (altered taste) affects the taste and texture of oral nutritional supplements (ONS) in cancer patients undergoing treatment. Dysgeusia can make it harder for patients to enjoy food and stick to their nutritional plans. In this study, 61 cancer patients—31 with dysgeusia and 30 without—rated the taste and texture of an ONS using special sensory methods. The results showed that patients with dysgeusia found the ONS to have stronger sweet, caramel, vanilla, and creamy flavors, while those without dysgeusia preferred more neutral, runny textures. Dysgeusia patients also reported feeling less hungry and more thirsty, suggesting that their sensory preferences affect how they feel during meals.
The findings suggest that dysgeusia patients might benefit from ONS that are creamier or smoother to reduce unpleasant tastes. It also highlights the need for personalized ONS formulations to improve taste, making it easier for these patients to stick to their nutritional needs. This research helps us better understand the sensory experiences of cancer patients with dysgeusia and supports the development of ONS that better meet their needs
"Minimal Residual Disease–Based End Point for Accelerated Assessment of Clinical Trials in Multiple Myeloma: A Pooled Analysis of Individual Patient Data From Multiple Randomized Trials"
Source
Qian Shi et al., Minimal Residual Disease–Based End Point for Accelerated Assessment of Clinical Trials in Multiple Myeloma: A Pooled Analysis of Individual Patient Data From Multiple Randomized Trials. JCO 0, JCO-24-02020 DOI:10.1200/JCO-24-02020 February 12, 2025.
Overview
Recent advances in treatment for multiple myeloma (MM) have improved patient survival, but there is a need for quicker ways to approve new therapies. This study looks at using minimal residual disease-negative complete response (MRD-CR) as a faster marker to predict long-term survival in patients with newly diagnosed MM (both transplant-eligible and transplant-ineligible) and those with relapsed or refractory MM.
The study analyzed data from 11 clinical trials involving 4,773 patients. It found that achieving MRD-CR at 9 or 12 months (using a specific threshold) strongly correlated with longer progression-free survival (PFS) and overall survival (OS) in these patients. The results suggest that MRD-CR could be a reliable early marker for predicting the success of new MM treatments, helping to speed up their approval process. This approach could be useful in future trials to test new therapies in MM patients.
"Recombinant human thrombopoietin does not promote platelet engraftment in newly diagnosed multiple myeloma patients following autologous stem cell transplantation"
Source
Wang, R., Cai, J., Chen, Z. et al. Recombinant human thrombopoietin does not promote platelet engraftment in newly diagnosed multiple myeloma patients following autologous stem cell transplantation. Sci Rep 15, 5393 (2025). https://doi.org/10.1038/s41598-025-89535-7 February 13, 2025.
Overview
This study aimed to evaluate the impact of recombinant human thrombopoietin (rhTPO) on platelet engraftment after autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma (NDMM). A total of 40 patients who received high-dose chemotherapy and ASCT were analyzed, with 26 receiving rhTPO and 14 in the control group.
The study found no significant difference between the two groups in terms of platelet engraftment time, neutrophil engraftment, or the number of blood cell transfusions. The hospitalization duration and blood transfusion rates were similar between the groups. However, rhTPO treatment resulted in higher hospitalization costs.
While rhTPO did not improve platelet recovery or reduce transfusions after ASCT, it did increase treatment costs.
"Extramedullary Myeloma in the Era of CAR T-cell and Bispecific Antibody Therapies"
Source
Larysa Sanchez, Shambavi Richard, Extramedullary Myeloma in the Era of CAR T-cell and Bispecific Antibody Therapies, Seminars in Hematology, 2025,ISSN 0037-1963, https://doi.org/10.1053/j.seminhematol.2025.02.001. February 12, 2025.
Overview
Despite progress in multiple myeloma treatments, there are still challenges, especially for high-risk patients such as the elderly, those with plasma cell leukemia, or patients with myeloma affecting the central nervous system or spreading beyond the bone marrow. While T-cell redirecting therapies (like CAR T-cell therapy and bispecific antibodies) have shown strong results in advanced myeloma, there is concern about how well these treatments can address high-risk forms, such as extramedullary myeloma (when myeloma cells spread outside the bone marrow). This review explores how these therapies are currently performing in patients with extramedullary disease and their potential impact on treatment outcomes.
"Heme promotes venetoclax resistance in multiple myeloma through MEK-ERK signaling and purine biosynthesis"
Source
Remya Nair, An H. Vu, Abigail K. Freer, Karanpreet S. Bhatia, Dongxue Wang, Milan R. Savani, Shannon M. Matulis, Sagar Lonial, David L. Jaye, Lawrence H. Boise, Seung-Yong Seo, Timothy W. Corson, Ajay K. Nooka, Shruti Bhatt, Samuel K. McBrayer, Vikas A. Gupta, Xin Hu, Benjamin G. Barwick, Amit R. Reddi, Mala Shanmugam; Heme promotes venetoclax resistance in multiple myeloma through MEK-ERK signaling and purine biosynthesis. Blood 2025; 145 (7): 732–747. doi: https://doi.org/10.1182/blood.2024025690 February 13, 2025.
Overview
Despite progress in multiple myeloma treatments, there are still challenges, especially for high-risk patients such as the elderly, those with plasma cell leukemia, or patients with myeloma affecting the central nervous system or spreading beyond the bone marrow. While T-cell redirecting therapies (like CAR T-cell therapy and bispecific antibodies) have shown strong results in advanced myeloma, there is concern about how well these treatments can address high-risk forms, such as extramedullary myeloma (when myeloma cells spread outside the bone marrow). This review explores how these therapies are currently performing in patients with extramedullary disease and their potential impact on treatment outcomes.
"Heme fuels venetoclax resistance in multiple myeloma"
Source
Mariateresa Fulciniti; Heme fuels venetoclax resistance in multiple myeloma. Blood 2025; 145 (7): 658–660. doi: https://doi.org/10.1182/blood.2024027671 February 13, 2025.
Overview
In a recent study, researchers found that heme, a natural substance in the body, plays a role in resistance to the drug venetoclax, which is used to treat multiple myeloma (MM). Heme is involved in producing energy within cells, but when its production is reduced, it makes MM cells more sensitive to venetoclax. The researchers showed that MM cells sensitive to venetoclax naturally produce less heme, so they absorb more heme from outside sources like food or broken red blood cells. However, adding extra heme makes MM cells less responsive to venetoclax. On the other hand, blocking the production of heme made the cells more sensitive to the drug.
The study also found that MEK-ERK signaling, a pathway inside cells, helps explain this resistance. When this pathway is activated, it can make cells less responsive to venetoclax. This research highlights how changes in a cell’s metabolism can affect how well cancer treatments work, and it suggests that targeting metabolic pathways like heme could improve treatment outcomes, especially for patients with resistant forms of MM.
"Lactate metabolism in clonal plasma cells and its therapeutic implications in multiple myeloma patients with elevated serum LDH level"
Source
Chawla, Y., Anderson, E.I., Smith, M. et al. Lactate metabolism in clonal plasma cells and its therapeutic implications in multiple myeloma patients with elevated serum LDH levels. Cancer Metab 13, 9 (2025). https://doi.org/10.1186/s40170-025-00379-1 February 13, 2025.
Overview
This study looked at the differences in metabolism between multiple myeloma (MM) cells from patients with high and low serum LDH (lactate dehydrogenase) levels, to find potential treatment targets. Researchers found that MM cells from patients with high serum LDH levels had higher levels of a protein called MCT1, which is involved in transporting lactate in and out of cells. When they blocked both MCT1 and its partner, MCT4, the MM cells from high LDH patients were more sensitive to treatment and died more easily. These findings suggest that targeting MCT1 and MCT4 could be a promising therapy for patients with high LDH levels in MM.
"Impact of Quadruplet Induction Therapy on Stem Cell Mobilization Yields in Newly Diagnosed Multiple Myeloma"
Source
Ryan Beechinor, Stepfanie Lam, Aaron Steele, Machelle Wilson, Jeffrey Fine, Ayman Ullah, Aaron Rosenberg, Impact of Quadruplet Induction Therapy on Stem Cell Mobilization Yields in Newly Diagnosed Multiple Myeloma, Transfusion Clinique et Biologique, 2025, ISSN 1246-7820, https://doi.org/10.1016/j.tracli.2025.02.001. February 13, 2025.
Overview
Daratumumab-containing quadruplet therapy is now a standard treatment for newly diagnosed multiple myeloma (NDMM) patients who are eligible for a stem cell transplant. However, since daratumumab can suppress the immune system, researchers wanted to see if it affects the ability to collect stem cells for transplant.
This study looked at 104 NDMM patients and compared stem cell collection between those who received a daratumumab-containing quadruplet therapy and those who had a traditional three-drug induction. The results showed that both groups successfully collected the required number of stem cells after their first attempt, meaning daratumumab did not significantly impact overall stem cell yield.
However, patients who received daratumumab needed more time for the apheresis procedure (a median of two days vs. one day in the non-daratumumab group). Because of this, the study highlights the importance of using supportive medications like granulocyte-colony stimulating factor (G-CSF) and plerixafor to improve stem cell collection.
These findings help guide best practices for stem cell collection in patients receiving daratumumab and may also impact the scheduling of apheresis machines to ensure efficient treatment.
"Overview of 1q abnormalities in multiple myeloma: scientific opinions from Italian experts"
Source
D’Agostino, M., Martello, M., De Paoli, L. et al. Overview of 1q abnormalities in multiple myeloma: scientific opinions from Italian experts. Ann Hematol (2025). https://doi.org/10.1007/s00277-025-06212-5 February 13, 2025.
Overview
Multiple myeloma (MM) is a blood cancer with a high level of genetic variation. One of the most common genetic changes in MM is the gain of extra material on the long arm of chromosome 1 (+1q). This alteration has been linked to treatment resistance, but the exact genetic factors behind this are still being studied.
Currently, a test called interphase fluorescence in situ hybridization (iFISH) is the standard way to detect +1q in MM. However, there is no universal guideline on how much extra +1q is needed for it to be considered clinically significant. Because iFISH has limitations, advanced sequencing methods may provide a more detailed picture of genetic abnormalities in MM.
Recent updates to the international staging system for MM now classify +1q as a high-risk feature. Research shows that +1q can affect how long remission lasts, suggesting that patients with this abnormality may need specialized treatment plans. However, because current data is inconsistent, doctors must consider +1q alongside other genetic and clinical factors when making treatment decisions. Ongoing studies will help clarify the full impact of +1q in MM and guide future treatment approaches.
Daratumumab-containing quadruplet therapy is now a standard treatment for newly diagnosed multiple myeloma (NDMM) patients who are eligible for a stem cell transplant. However, since daratumumab can suppress the immune system, researchers wanted to see if it affects the ability to collect stem cells for transplant.
This study looked at 104 NDMM patients and compared stem cell collection between those who received a daratumumab-containing quadruplet therapy and those who had a traditional three-drug induction. The results showed that both groups successfully collected the required number of stem cells after their first attempt, meaning daratumumab did not significantly impact overall stem cell yield.
However, patients who received daratumumab needed more time for the apheresis procedure (a median of two days vs. one day in the non-daratumumab group). Because of this, the study highlights the importance of using supportive medications like granulocyte-colony stimulating factor (G-CSF) and plerixafor to improve stem cell collection.
These findings help guide best practices for stem cell collection in patients receiving daratumumab and may also impact the scheduling of apheresis machines to ensure efficient treatment.
"PHLPP and LAMP2 predict favorable treatment response and survival in multiple myeloma patients who receive induction treatment with bortezomib"
Source
Han, Q., Han, W., Li, C. et al. PHLPP and LAMP2 predict favorable treatment response and survival in multiple myeloma patients who receive induction treatment with bortezomib. Ir J Med Sci (2025). https://doi.org/10.1007/s11845-025-03879-7 February 14, 2025.
Overview
Researchers have identified two proteins, PHLPP and LAMP2, that may help predict how well multiple myeloma (MM) patients respond to bortezomib, a common treatment. In this study, higher levels of PHLPP were linked to increased LAMP2 levels in bone marrow plasma cells. Patients with elevated levels of both proteins were more likely to achieve remission after treatment.
Additionally, those with high PHLPP and LAMP2 levels experienced longer progression-free survival (PFS), meaning their disease stayed under control for a longer period. However, these proteins did not significantly impact overall survival (OS).
These findings suggest that measuring PHLPP and LAMP2 levels before treatment could help identify patients who are more likely to benefit from bortezomib. Further research may determine whether these proteins can be used as biomarkers to guide treatment decisions and improve outcomes for MM patients.
"Sustained Improvement in Health-Related Quality of Life in Transplant-Ineligible Newly Diagnosed Multiple Myeloma Treated With Daratumumab, Lenalidomide, and Dexamethasone: MAIA Final Analysis of Patient-Reported Outcome"
Source
Perrot, A., Facon, T., Plesner, T., Usmani, S.Z., Kumar, S., Bahlis, N.J., Hulin, C., Orlowski, R.Z., Nahi, H., Mollee, P., Ramasamy, K., Roussel, M., Jaccard, A., Delforge, M., Karlin, L., Arnulf, B., Chari, A., Wang, G., Gupta-Werner, N., Kaila, S., Pei, H., Matt, K., Gries, K.S., Carson, R., Borgsten, F. and Weisel, K. (2025), Sustained Improvement in Health-Related Quality of Life in Transplant-Ineligible Newly Diagnosed Multiple Myeloma Treated With Daratumumab, Lenalidomide, and Dexamethasone: MAIA Final Analysis of Patient-Reported Outcomes. Eur J Haematol. https://doi.org/10.1111/ejh.14392 February 14, 2025.
Overview
A long-term analysis of the phase III MAIA study found that adding daratumumab to lenalidomide and dexamethasone (D-Rd) improves the quality of life for patients with newly diagnosed multiple myeloma (NDMM) who are not eligible for a stem cell transplant. The study followed patients for a median of 64.5 months and assessed their overall health, physical function, pain, and fatigue using a standard questionnaire.
Results showed that patients treated with D-Rd had sustained improvements in their health and well-being over five years compared to those receiving lenalidomide and dexamethasone alone (Rd). These benefits were seen across different patient groups, including older adults and those with bone lesions. By year three, more D-Rd patients reported meaningful improvements in overall health, physical function, pain, and fatigue compared to those on Rd.
These findings highlight the long-term benefits of D-Rd in improving quality of life for transplant-ineligible NDMM patients, reinforcing its role as a preferred treatment option.
"Maraviroc enhances Bortezomib sensitivity in multiple myeloma by inhibiting M2 macrophage polarization via PI3K/AKT/RhoA signaling pathway in macrophages"
Source
Yang, H., He, Y., Qu, F. et al. Maraviroc enhances Bortezomib sensitivity in multiple myeloma by inhibiting M2 macrophage polarization via PI3K/AKT/RhoA signaling pathway in macrophages. Cell Div 20, 5 (2025). https://doi.org/10.1186/s13008-025-00145-1 February 14, 2025.
Overview
Multiple myeloma (MM) often becomes resistant to treatment, leading to relapse. Researchers have identified the protein CCR5 as a potential treatment target. In this study, they explored whether blocking CCR5 with the drug Maraviroc (MVC) could improve the effectiveness of the chemotherapy drug Bortezomib. They focused on how CCR5 influences M2 macrophages—immune cells that can help cancer cells grow and resist treatment.
The study found that MM patients had higher levels of CCL3, CCR5, and M2 macrophages, which were linked to drug resistance. MM cells released CCL3, which activated CCR5 and increased M2 macrophage activity. This process helped MM cells grow, made them harder to kill, and reduced their response to Bortezomib. However, when CCR5 was blocked with MVC, M2 macrophage activity decreased, and MM cells became more sensitive to Bortezomib. These results were seen both in lab tests and in mice with MM.
By targeting CCR5, MVC may help overcome drug resistance in MM by reducing harmful immune cell activity. This study suggests that blocking CCR5 could be a promising new strategy to improve MM treatment.
"Real-world evidence of Carfilzomib, Lenalidomide and Dexamethasone (KRD) Scheme in patients with relapsed / refractory multiple myeloma"
Source
Garcia-Guiñon, A., Charry, P.A., Jimenez, M. et al. Real-world evidence of Carfilzomib, Lenalidomide and Dexamethasone (KRD) Scheme in patients with relapsed / refractory multiple myeloma. Ann Hematol (2025). https://doi.org/10.1007/s00277-025-06240-1 February 15, 2025.
Overview
The combination of Kyprolis® (carfilzomib), Revlimid® (lenalidomide), and dexamethasone (KRd) is a common treatment for patients with relapsed or refractory multiple myeloma (RRMM), but there is limited real-world data on its effectiveness and safety. This study analyzed KRd treatment outcomes in hospitals across the Catalan region using medical records from 194 patients. The average patient age was 64, and all had previously received bortezomib, with some also having been treated with thalidomide or lenalidomide.
The study found that 73% of patients responded to KRd treatment, with 37% achieving a complete response or better. Response rates were influenced by disease stage, prior treatments, and previous lenalidomide use. Patients had a median progression-free survival of 26 months, and 70% were still alive after two years. The stage of the disease and LDH levels were important factors in predicting survival.
Overall, KRd showed good effectiveness and a safety profile similar to what was observed in phase III clinical trials. These findings support its continued use as a treatment option for RRMM in real-world clinical practice.
"Threonine and tyrosine kinase promotes multiple myeloma progression by regulating regucalcin expression"
Source
Xiaofeng Zhu, Zuxi Feng, Xiaohuan Peng, Tianning Di, YanHong Li, Jun Bai, Tao Ma, Lijuan Li, Liansheng Zhang, Threonine and tyrosine kinase promotes multiple myeloma progression by regulating regucalcin expression, Experimental Cell Research, 2025, 114454, ISSN 0014-4827, https://doi.org/10.1016/j.yexcr.2025.114454. February 15, 2025.
Overview
Researchers are looking for new ways to slow the growth of multiple myeloma (MM) and improve its treatment options. A recent study explored the role of a protein called threonine and tyrosine kinase (TTK) in MM.
The study found that MM patients had higher levels of TTK compared to healthy individuals. When researchers reduced TTK levels in MM cells, the cancer cells stopped growing, entered a resting phase, and were more likely to die. In contrast, increasing TTK levels made MM cells grow faster and resist cell death.
The researchers also discovered that TTK affects another protein called regucalcin (RGN), which is involved in cell growth and survival. When TTK levels were high, RGN levels were low, which helped MM cells survive and multiply. In a mouse model, blocking TTK slowed tumor growth, suggesting it could be a promising drug target.
These findings suggest that targeting TTK could be a new way to treat multiple myeloma. More research is needed to develop therapies that block TTK and test their effectiveness in patients.
"Antibody response to Pneumococcal, Influenza, and COVID-19 vaccination in patients with Multiple Myeloma: Vaccination efficacy in Multiple Myeloma Patients"
Source
Pranjal Singh, Charanpreet Singh, Kamaljeet Kamaljeet, VA Arun, RK Ratho, Archana Angrup, Arihant Jain, Sreejesh Sreedharanunni, Gaurav Prakash, Alka Khadwal, Pankaj Malhotra, Antibody response to Pneumococcal, Influenza, and COVID-19 vaccination in patients with Multiple Myeloma: Vaccination efficacy in Multiple Myeloma Patients, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.02.006. February 15, 2025.
Overview
People with multiple myeloma (MM) have a weakened immune system, making them more vulnerable to infections. Experts recommend vaccines for common respiratory illnesses, but there is limited data on how well they work in MM patients.
A recent study looked at the effectiveness of pneumococcal, influenza, and COVID-19 vaccines in newly diagnosed MM patients. Researchers tracked 30 patients who received these vaccines between January and June 2021. After vaccination, antibody levels increased significantly for all three infections. About 50–60% of patients developed a strong immune response (seroconversion), meaning their antibody levels rose at least four times.
No serious side effects were reported. Over six months, 10 patients developed respiratory infections, but none were caused by pneumococcus, influenza, or COVID-19.
These results suggest that vaccines can help MM patients build immunity against serious infections. However, since not all patients responded to the vaccines, more research is needed to improve protection strategies.
"Matching-adjusted indirect comparison of daratumumab-pomalidomide-dexamethasone and pomalidomide-bortezomib-dexamethasone in relapsed/refractory multiple myeloma"
Source
Wee Joo Chng, David Bin-Chia Wu, Cathy Kwang-Wei Wu, Aaron Springford, Caitlin H Daly, Sung-Hoon Jung, Matching-adjusted indirect comparison of daratumumab-pomalidomide-dexamethasone and pomalidomide-bortezomib-dexamethasone in relapsed/refractory multiple myeloma, Clinical Lymphoma Myeloma and Leukemia, 2025, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2025.02.007. February 15, 2025.
Overview
For patients with multiple myeloma (MM), lenalidomide is often used as a first-line treatment. However, when the disease no longer responds to lenalidomide, it becomes harder to treat. Two other treatment options, daratumumab, pomalidomide, and dexamethasone (DPd), and pomalidomide, bortezomib, and dexamethasone (PVd), have shown effectiveness in patients who have already been treated with lenalidomide. But there’s limited data comparing these two options directly.
A study used data from two major trials, APOLLO and OPTIMISMM, to compare the effectiveness of DPd and PVd. The results showed that DPd was likely to provide better progression-free survival (PFS) than PVd. Specifically, the risk of disease progression was 41% lower with DPd. Although DPd also seemed to improve overall survival (OS), the evidence wasn’t strong enough to confirm this for sure.
DPd appears to be more effective in improving PFS compared to PVd in patients with relapsed or refractory MM. However, more research through direct trials or real-world data is needed to confirm these findings.
"A Novel Two-Part Mixture Model for the Incidence and Time Course of Cytokine Release Syndrome After Elranatamab Dosing in Multiple Myeloma Patients"
Source
Irby, D., Hibma, J., Elmeliegy, M., Wang, D., Vandendries, E., Poels, K., Shtylla, B. and Williams, J.H. (2025), A Novel Two-Part Mixture Model for the Incidence and Time Course of Cytokine Release Syndrome After Elranatamab Dosing in Multiple Myeloma Patients. Clin Pharmacol Ther. https://doi.org/10.1002/cpt.3533 February 16, 2025. .
Overview
Cytokine release syndrome (CRS) is a common side effect of T-cell redirecting therapies like bispecific antibodies (BsAbs), which are used to treat cancers like multiple myeloma. CRS can be difficult to predict and measure accurately, especially when using standard models that don’t account for changes over time or different doses.
A recent study used a more advanced method, a two-part mixture model, to better understand how CRS develops after treatment with elranatamab, a BsAb targeting myeloma cells and T cells. The study found that higher levels of elranatamab exposure were linked to a higher chance of CRS. Additionally, early exposure to the drug increased the likelihood of CRS over time, but using premedication like steroids or IL-6 inhibitors helped reduce the risk.
This study is the first to use a Markov model to track CRS events after BsAb therapy, offering a better way to understand and predict CRS. This approach could help improve the development and safety of future BsAb treatments.
"Completion of Distress Screening and Correlates of Distress Score in Patients With Multiple Myeloma at Initial Evaluation at a Transplant Center"
Source
Estrada-Merly, N., Wu, J.F., Pezzin, L.E., Nataliansyah, M.M. and D'Souza, A. (2025), Completion of Distress Screening and Correlates of Distress Score in Patients With Multiple Myeloma at Initial Evaluation at a Transplant Center. Eur J Haematol. https://doi.org/10.1111/ejh.14394 February 16, 2025.
Overview
A recent study explored the use of the distress thermometer (DT) to measure emotional and psychological distress in patients newly diagnosed with multiple myeloma (MM). The DT survey was given to 1,011 patients at their first consultation at an academic center from 2015 to 2022. The study found that 68% of patients completed the survey, and certain factors influenced whether patients filled it out. These included race, neighborhood vulnerability, physical health, and the year of consultation. Patients who didn’t complete the survey were also less likely to undergo treatments like autologous stem cell transplantation.
Among those who completed the survey, most had low distress, with 22% reporting no distress at all. However, factors like being female and having a more advanced stage of MM were linked to higher distress scores.
The findings highlight some challenges in using the DT survey to fully understand the needs of high-risk patients. It suggests that relying solely on this tool may miss important issues faced by certain groups, such as non-Hispanic Black patients or those from socially vulnerable neighborhoods.
"Diagnosis and Management of Monoclonal Gammopathy of Undetermined Significance: A Review"
Source
Liu Y, Parks AL. Diagnosis and Management of Monoclonal Gammopathy of Undetermined Significance: A Review. JAMA Intern Med. Published online February 17, 2025. doi:10.1001/jamainternmed.2024.8124
Overview
Monoclonal gammopathy of unknown significance (MGUS) is a condition where there is a small amount of abnormal protein in the blood, but no symptoms or organ damage. It affects nearly 5% of adults. The main goal in managing MGUS is to tell it apart from more serious conditions like multiple myeloma (MM) or amyloidosis, which can cause harm to organs.
MGUS doesn't cause symptoms and usually has low amounts of abnormal proteins and plasma cells. However, it needs to be carefully watched to ensure it doesn't develop into a more serious illness. Most people with MGUS have a very low risk of it turning into cancer—about 0.5% to 1% each year.
Doctors determine how to manage MGUS based on factors like the type of abnormal protein, its concentration, and the ratio of light chains in the blood. People with low-risk MGUS can typically be monitored with regular lab tests and don't need more invasive tests like bone marrow biopsies. Those with a higher risk may need additional tests, including bone marrow biopsies and imaging to check for signs of MM.
New research and advanced molecular testing could help doctors predict which patients are at the highest risk of developing cancer, ensuring the right people get more intense monitoring or treatment, while avoiding unnecessary tests for those at low risk. Ongoing clinical trials are exploring the best ways to screen, monitor, and treat MGUS to improve patient outcomes.
"A 2D-STI echocardiographic diagnostic model established for cardiac amyloidosis complicated with multiple myeloma"
Source
Hongmiao Shen, Jiali Fan, Xingyue Wu, Yue Huang, Hongying You, Zhi Yan, Yan Xie, Weiqin Yao, Shuang Yan, Yingying Zhai, Jingjing Shang, Song Jin, Bingyuan Zhou, Depei Wu, Chengcheng Fu, A 2D-STI echocardiographic diagnostic model established for cardiac amyloidosis complicated with multiple myeloma, International Journal of Cardiology, 2025, 133041, ISSN 0167-5273, https://doi.org/10.1016/j.ijcard.2025.133041. February 17, 2025.
Overview
A recent study focused on understanding the characteristics of multiple myeloma (MM) with amyloidosis (AL) and testing the effectiveness of a special type of echocardiogram, called 2D speckle tracking imaging (2D-STI), for diagnosing heart problems in MM patients with amyloidosis (MM-CA).
The study looked at 359 MM patients and divided them into groups based on whether they had amyloidosis and whether their heart was affected. Patients with MM-AL were more likely to experience heart failure and less likely to have bone pain compared to those without amyloidosis.
The study found that an echocardiographic model using multiple heart-related measurements (including left ventricular ejection fraction, pulmonary artery pressure, and global strain) had the best accuracy for diagnosing cardiac amyloidosis. This model showed a high accuracy rate of 90.8%, with high sensitivity and specificity.
While MM with and without amyloidosis shared similar symptoms, this new echocardiographic method can be a useful tool for early detection of heart issues in patients with MM and amyloidosis.
"Prognostic impact of patient-reported symptoms in multiple myeloma"
Source
Nadine Abdallah, Arwa Bohra, Aytaj Mammadzadeh, Francis Buadi, Prashant Kapoor, Angela Dispenzieri, Morie Gertz, Suzanne Hayman, Mohammed ElHaj, David Dingli, Joselle Cook, Moritz Binder, Yi Lin, Taxiarchis Kourelis, Rahma Warsame, Carrie Thompson, Terri Menser, S. Vincent Rajkumar, Shaji Kumar; Prognostic impact of patient-reported symptoms in multiple myeloma. Blood Adv 2025; 9 (4): 884–892. doi: https://doi.org/10.1182/bloodadvances.2024014232 February 25, 2025.
Overview
A study at Mayo Clinic investigated how patient-reported symptoms, including fatigue, pain, and quality of life (QOL), affect survival in people with newly diagnosed multiple myeloma (MM). The study used a simple 3-item questionnaire called the "Hematology Patient-Reported Symptom Screen" (HPRSS) to assess these symptoms.
The study found that fatigue, pain, and poor quality of life were linked to shorter progression-free survival (PFS) and overall survival (OS). Certain factors, like older age, being female, having comorbidities, and higher disease severity, were associated with more fatigue, pain, and lower QOL. Fatigue and low QOL were independently tied to lower overall survival, even when considering other factors like disease stage or treatment status.
The study also showed that combining the HPRSS scores into one composite score helped predict survival outcomes, with distinct survival rates for different symptom groups. This suggests that monitoring patient-reported symptoms can provide important insights into prognosis and guide treatment decisions in MM.
"The roadmap to integrate diversity, equity, and inclusion in hematology clinical trials: an American Society of Hematology initiative"
Source
Alice Kuaban, Alysha K. Croker, Jeffrey Keefer, Leonard A. Valentino, Barbara E. Bierer, Stephen Boateng, Donna DiMichele, Patrick Fogarty, C. Michael Gibson, Anna M. Hood, Lloryn Hubbard, Antonella Isgrò, Karin Knobe, Leslie Lake, Iman Martin, Michel Reid, Jonathan C. Roberts, Wendy Tomlinson, Lanre Tunji-Ajayi, Harriette G.C. Van Spall, Caroline Voltz-Girolt, Allison P. Wheeler, Alan E. Mast, Stephanie Seremetis; The roadmap to integrate diversity, equity, and inclusion in hematology clinical trials: an American Society of Hematology initiative. Blood Adv 2025; 9 (4): 687–695. doi: https://doi.org/10.1182/bloodadvances.2024013945 February 25, 2025
Overview
Designing clinical trials for blood disorders can be challenging because the patient groups are often small and not representative of the broader population. The American Society of Hematology (ASH) launched a project to address these challenges and make clinical trials more diverse, equitable, and inclusive. This initiative, called the "roadmap," involved discussions with experts from around the world to identify key issues and solutions.
The project highlighted eight main areas that need attention:
- Standardizing how demographic information is recorded.
- Involving people with lived experiences throughout the study.
- Recognizing how biases can limit patient enrollment.
- Ensuring fairness in how patients are chosen for trials.
- Expanding eligibility requirements.
- Using decentralized trial designs.
- Improving access to information about trials.
- Increasing involvement of community-based physicians.
- These efforts aim to create more inclusive trials that better represent the patient population, leading to better research, clinical decisions, and patient care.
Hematologic diseases like hemophilia and sickle cell disease are often considered rare because they affect small populations. This makes it hard to enroll diverse patients in clinical trials, as there are limited opportunities for participation and various biases can prevent certain groups from being included. To address these issues, ASH is committed to improving the diversity of clinical trials and ensuring they reflect the true diversity of the affected communities.
"Application of Branched-Polyethyleneimine/Polyacrylic-Acid Self-assembled Nanocapsules Supported by Mesoporous Spherical Shell Structures in the Treatment of Multiple Myeloma, Colloids and Surfaces A: Physicochemical and Engineering Aspects"
Source
Liyuan Wang, Mengyu Xu, Meifang Xu, Xiaoqi Li, Hao Zheng, Lijuan Wang, Yanxi Zhu, Application of Branched-Polyethyleneimine/Polyacrylic-Acid Self-assembled Nanocapsules Supported by Mesoporous Spherical Shell Structures in the Treatment of Multiple Myeloma, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2025, 136461, ISSN 0927-7757, https://doi.org/10.1016/j.colsurfa.2025.136461. February 18, 2025.
Overview
The chemotherapy drug Doxil® (doxorubicin), or DOX, used to treat multiple myeloma (MM) can cause serious side effects. Although using nano-delivery systems has helped improve how well the drug works, its delivery efficiency remains a challenge.
Researchers have developed a new method to improve the delivery of DOX using hollow mesoporous titanium dioxide nanoparticles (H-mTiO2). These nanoparticles were modified with special chemicals (branched polyethyleneimine, polyacrylic acid, and A6 short peptide) to make the drug more efficiently target cancer cells. The new system showed a release rate of about 80% of the drug and increased the drug's concentration in tumors, significantly stopping multiple myeloma cell growth in lab tests.
Further testing in mice with multiple myeloma tumors showed that this new drug delivery method not only worked well at fighting the tumor but also reduced harmful side effects on healthy cells. This suggests that the targeted nano-delivery system could be a valuable tool for treating multiple myeloma.
"Clonal plasma cell proportion in the synthetic phase identifies a unique high-risk cohort in multiple myeloma"
Source
Zanwar, S., Jevremovic, D., Kapoor, P. et al. Clonal plasma cell proportion in the synthetic phase identifies a unique high-risk cohort in multiple myeloma. Blood Cancer J. 15, 20 (2025). https://doi.org/10.1038/s41408-025-01232-w February 18, 2025.
Overview
In patients with newly diagnosed multiple myeloma (NDMM), identifying high-risk cases is crucial for treatment planning. This study looked at the proportion of clonal plasma cells in the S-phase of the cell cycle as a possible marker for high-risk patients. The S-phase is a phase in the cell cycle where DNA is synthesized, and high levels of plasma cells in this phase can indicate a more aggressive disease.
Among 823 patients, 16% had S-phase levels of 2% or more. These patients had significantly worse outcomes, with a median progression-free survival (PFS) of 1.4 years, compared to 2.9 years for patients with lower S-phase levels. The median overall survival (OS) was also much shorter at 3.9 years for those with high S-phase, compared to 9.2 years for those with lower levels.
The study showed that having S-phase ≥2% was an independent predictor of worse survival outcomes, even after adjusting for other factors like age, kidney function, and treatment strategies. Patients with elevated S-phase were 2.5 times more likely to experience progression within 18 months of starting treatment. Importantly, when both elevated S-phase and high-risk genetic markers were present, the patients had the worst survival outcomes.
These findings suggest that S-phase ≥2% is a valuable and independent marker for predicting worse outcomes in NDMM, helping doctors better assess patient risk and treatment options.
"Co-Occurrence of Cytogenetic Abnormalities and High-Risk Disease in Newly Diagnosed and Relapsed/Refractory Multiple Myeloma"
Source
Martin F. Kaiser et al., Co-Occurrence of Cytogenetic Abnormalities and High-Risk Disease in Newly Diagnosed and Relapsed/Refractory Multiple Myeloma. JCO 0, JCO-24-01253 DOI:10.1200/JCO-24-01253 February 18, 2025.
Overview
Although survival for multiple myeloma (MM) patients has improved, some still face poor outcomes due to high-risk disease. Identifying these high-risk cases early is important for improving treatment. This study investigated how the presence of high-risk cytogenetic abnormalities (HRCAs) in newly diagnosed (NDMM) and relapsed/refractory (RRMM) patients affects their prognosis.
The study analyzed data from 24 clinical trials involving nearly 14,000 patients. Researchers focused on patients with one HRCA or two or more HRCAs. They found that patients with two or more HRCAs had a much higher risk of poor outcomes. Specifically, these patients had a 2.28 times higher risk of disease progression (PFS) and a 2.94 times higher risk of death (OS) compared to those with fewer or no HRCAs.
These results were consistent across treatment types and patient groups, including those with relapsed disease and those eligible for a transplant. The findings emphasize the importance of identifying patients with multiple HRCAs so that doctors can tailor treatment strategies to better address the needs of these high-risk patients.
"Comparison of Standard-of-Care Idecabtagene Vicleucel and Ciltacabtagene Autoleucel in Relapsed/Refractory Multiple Myeloma"
Source
Doris K. Hansen et al., Comparison of Standard-of-Care Idecabtagene Vicleucel and Ciltacabtagene Autoleucel in Relapsed/Refractory Multiple Myeloma. JCO 0, JCO-24-01730 DOI:10.1200/JCO-24-01730 February 18, 2025.
Overview
Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are two advanced CAR T-cell therapies targeting B-cell maturation antigen (BCMA), showing strong results in treating relapsed/refractory multiple myeloma (RRMM). This study compares their safety, effectiveness, and survival outcomes.
Data from 641 patients treated with either ide-cel (386 patients) or cilta-cel (255 patients) were reviewed. After 12 months of follow-up, the results showed that cilta-cel led to better treatment responses, with more patients achieving a complete response and longer progression-free survival (PFS) and overall survival (OS) compared to ide-cel. However, cilta-cel also came with a higher risk of severe side effects, such as cytokine release syndrome (CRS), infections, second cancers, and delayed neurotoxicity.
Both therapies showed no major differences in terms of severe cytopenia, neurotoxicity syndrome, or non-relapse mortality. Overall, cilta-cel had better efficacy but was linked to more frequent and severe toxicities.
"Mass Spectrometry–Based Proteomics in Clinical Diagnosis of Amyloidosis and Multiple Myeloma: A Review"
Source
Kratka, K., Sistik, P., Olivkova, I., Kusnierova, P., Svagera, Z. and Stejskal, D. (2025), Mass Spectrometry–Based Proteomics in Clinical Diagnosis of Amyloidosis and Multiple Myeloma: A Review (2012–2024). J Mass Spectrom, 60: e5116. https://doi.org/10.1002/jms.5116 February 19, 2025.
Overview
Proteomics, the study of proteins, is becoming an important tool in hospital diagnostic laboratories, especially with the advancement of mass spectrometry techniques. This review explores how proteomic analysis helps identify diseases, particularly through the study of protein biomarkers. It highlights the challenges in identifying disease-causing proteins, which can undergo changes (called posttranslational modifications or PTMs) like phosphorylation and glycosylation. These changes are crucial for normal protein function but can cause diseases if disrupted.
Traditional methods like electrophoresis and immunochemistry are commonly used to detect proteins, but they often lack precision and can lead to false results. For example, diagnosing conditions like multiple myeloma and amyloidosis can be inaccurate with these older methods. Mass spectrometry, on the other hand, offers higher sensitivity and accuracy, making it ideal for detecting specific proteins, such as in minimal residual disease (MRD) in multiple myeloma and amyloid typing in amyloidosis. The review emphasizes the potential of mass spectrometry to revolutionize clinical proteomics and improve diagnostics, encouraging its wider use in labs.
"High WEE1 expression is independently linked to poor survival in multiple myeloma"
Source
Simhal, A.K., Firestone, R.S., Oh, J.H. et al. High WEE1 expression is independently linked to poor survival in multiple myeloma. Blood Cancer J. 15, 22 (2025). https://doi.org/10.1038/s41408-025-01230-y February 20, 2025.
Overview
Current methods for predicting outcomes in multiple myeloma (MM) focus on disease burden and a few specific genetic changes. However, gene expression panels have the potential to predict clinical outcomes but are not yet used in practice. The WEE1 gene, which plays a key role in cell cycle regulation, is often altered in various cancers, but its role in MM has not been fully explored.
In this study, researchers analyzed a large MM dataset (MMRF CoMMpass) and found that WEE1 expression levels could help predict patient outcomes. They identified two groups based on WEE1 expression: a high-risk group (top 1/3) and a low-risk group (bottom 1/3). The high-risk group had a significantly worse progression-free survival (PFS). These results were confirmed in two other clinical trials (Total Therapy 2 and 3).
The study showed that WEE1 expression could predict outcomes independently of other known biomarkers. Abnormal WEE1 expression was linked to changes in important pathways, including the P53 pathway, which is involved in cancer development. These findings suggest that measuring WEE1 expression could become a useful tool for predicting outcomes in newly diagnosed MM patients and could support research into WEE1 inhibitors as a potential treatment option.
"Thrombotic events in patients with multiple myeloma and their impact on overall survival"
Source
Chen, H., Zhang, Y., Wang, Z., Wu, L., Fei, X., Wei, W., … Zhou, F. (2025). Thrombotic events in patients with multiple myeloma and their impact on overall survival. Hematology, 30(1). https://doi.org/10.1080/16078454.2025.2464316 February 19, 2025.
Overview
Thrombotic events (TEs), which include blood clots, are common and serious complications in patients with newly diagnosed multiple myeloma (NDMM). This study aimed to identify factors that increase the risk of thrombosis and to understand how TEs affect the survival of myeloma patients.
The study analyzed 181 patients with NDMM who were treated at a hospital between July 2020 and March 2024. It found that 11% of patients developed TEs, with 8.3% having venous thrombosis and 2.8% having arterial thrombosis. The patients who developed TEs were older than those who did not (70 years vs. 64 years).
The study showed that age is a key risk factor for developing TEs, and these events negatively impact the overall survival of myeloma patients. Those with arterial thrombosis had a more severe reduction in survival than those with venous thrombosis. The results suggest that careful management of blood clot prevention (thromboprophylaxis) is especially important for older myeloma patients.
"Interimsanalyse von IMROZ publiziert"
Source
Borchers, M. Interimsanalyse von IMROZ publiziert. InFo Hämatol Onkol 28, 32 (2025). https://doi.org/10.1007/s15004-025-0851-y February 20, 2025.
Overview
In patients with newly diagnosed multiple myeloma (NDMM) who are not eligible for a transplant, adding the anti-CD38 antibody isatuximab (Isa) to a treatment regimen of bortezomib, lenalidomide, and dexamethasone (VRd) appears to offer better progression-free survival (PFS) compared to VRd alone. This conclusion comes from the second interim analysis of the phase III IMROZ study, which followed patients for almost five years.
After a median follow-up of nearly 60 months, the PFS rate was 63.2% for the Isa-VRd group, compared to 45.2% for those on VRd alone. This represents a significant improvement (hazard ratio [HR] for progression or death 0.60; p < 0.001). The study involved 446 patients, with a median age of 72, who were randomly assigned to either the Isa-VRd treatment or VRd alone.
While the overall survival (OS) data are not yet finalized, the 60-month OS estimate was slightly higher in the Isa-VRd group (72.3%) compared to the VRd group (66.3%). Fewer people died from progression-related causes in the Isa-VRd group (4.9% vs. 12.2%), which suggests the combination may help prevent the disease from advancing more effectively.
However, the Isa-VRd combination did come with some additional risks. More patients in the Isa-VRd group experienced deaths from adverse events (11% vs. 5.5%) and developed second primary cancers (8.4% vs. 4.4%). The rate of serious side effects and infections was also slightly higher in the Isa-VRd group, and more patients experienced severe neutropenia.
These findings suggest that adding isatuximab to standard treatment could help manage multiple myeloma more effectively, although it comes with some increased risks.
"Deciphering response dynamics and treatment resistance from circulating tumor DNA after CAR T-cells in multiple myeloma"
Source
Hosoya, H., Carleton, M., Tanaka, K. et al. Deciphering response dynamics and treatment resistance from circulating tumor DNA after CAR T-cells in multiple myeloma. Nat Commun 16, 1824 (2025). https://doi.org/10.1038/s41467-025-56486-6 February 20, 2025. n, H., Zhang, Y., Wang, Z., Wu, L., Fei, X., Wei, W., … Zhou, F. (2025). Thrombotic events in patients with multiple myeloma and their impact on overall survival. Hematology, 30(1). https://doi.org/10.1080/16078454.2025.2464316 February 19, 2025.
Overview
Despite advances in treatment, patients with multiple myeloma (MM) will relapse. Researchers developed a new approach using circulating tumor DNA (ctDNA) to better understand the tumor's genetics, track treatment progress, and detect early signs of relapse in MM patients.
The study analyzed 412 samples from 64 patients, including those with newly diagnosed or relapsed/refractory MM. It found that ctDNA levels were closely linked to important clinical markers and patient outcomes. The researchers also expanded this approach to track CAR-specific cell-free DNA (CAR-cfDNA) in patients receiving anti-BCMA CAR T-cell therapy.
They found that ctDNA levels after CAR T-cell therapy were connected to how long it took for the disease to progress. Additionally, ctDNA from blood samples was able to detect measurable residual disease (MRD), which matched results from bone marrow tests. The study showed that ctDNA-MRD could predict relapse and identify new treatment-resistant cancer cells.
These results suggest that ctDNA can play an important role in the molecular analysis and ongoing monitoring of MM, helping to improve how the disease is tracked and treated.