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 May 2024 edition.
The IMF team of medical editors has provided overviews of key studies. Yet, we encourage you to visit the actual articles in the journals for full details and to increase your understanding. Check the IMF Newsroom monthly for updates like this one.
In the Journals (Key Myeloma Research in May 2024)
"Autologous-allogeneic versus autologous tandem stem cell transplantation and maintenance therapy with thalidomide for multiple myeloma patients under 60 years of age: a prospective, phase II study"
Source
Kröger N, Wulf G, Hegenbart U, Burchert A, Stelljes M, Gagelmann N, Brecht A, Kaufmann M, Müller L, Ganser A, Wolf D, Bethge W, Bornhäuser M, Kiehl M, Wagner E-M, Schmid C, Reinhardt HC, Kobbe G, Salwender H, Heinicke T, Kropff M, Heinzelmann M, Ayuk F, Trümper L, Neubauer A, Völp A, Kluychnikov E, Schönland S, Wolschke C. Autologous-allogeneic versus autologous tandem stem cell transplantation and maintenance therapy with thalidomide for multiple myeloma patients under 60 years of age: a prospective, phase II study. Haematologica 2024;109(5):1469-1479; https://doi.org/10.3324/haematol.2023.282920.
Overview
Researchers did a study to compare two different stem cell transplant treatments for multiple myeloma.The study included 217 patients with an average age of 51 years old.
One group got an autologous-allogeneic tandem stem cell transplant (alloTSCT). This means they first got their own stem cells transplanted back, then later got stem cells from a donor. After the transplants, they took the drug thalidomide for 2 years.
The other group just got two autologous transplants of their own stem cells (autoTSCT), with thalidomide for 2 years after.
The researchers looked at how long patients lived without their cancer coming back (progression-free survival or PFS). They also looked at overall survival.
After 4 years, 47% of the alloTSCT group and 35% of the autoTSCT group were alive without their cancer progressing. This difference increased over time but was not statistically significant.
Patients getting alloTSCT had a higher risk of complications and death not from cancer. But they had a significantly lower risk of their cancer relapsing or progressing compared to autoTSCT.
Overall survival at 4 and 8 years was similar between the two groups.
In conclusion, while alloTSCT reduced cancer relapse more than autoTSCT over a 10-year follow-up, it did not significantly improve progression-free survival. More research is still needed.
Impact of race and ethnicity on early mortality in multiple myeloma: a SEER analysis
Source
Wei JX, Shastri A, Sica RA, Mantzaris I, Kornblum N, Shah U, Janakiram M, Gritsman K, Verma A, Goldfinger M, Cooper D, Shah N. Impact of race and ethnicity on early mortality in multiple myeloma: a SEER analysis. Haematologica 2024;109(5):1480-1486; https://doi.org/10.3324/haematol.2023.283304.
Overview
Over the last 20 years, treatments for multiple myeloma have improved, helping patients live longer. However, some patients still die within 2 years of diagnosis. This is called early mortality.
Researchers used data from cancer registries in the United States from 2000-2019 to study factors that may contribute to early mortality in multiple myeloma patients. They found that patients diagnosed between 2000-2005, older patients, male patients, and patients from certain racial minority groups (non-Hispanic Black and Hispanic) had higher chances of dying within 2 years.
Of these factors, being from a racial minority group was linked to lower overall survival at 2 years. The researchers looked at whether income level, which can impact access to care, explained these racial differences. However, they found that race had a distinct relationship with early mortality, regardless of income level.
Further analysis reinforced that race itself was a risk factor for early death in multiple myeloma, separate from income. The researchers discuss potential reasons for these racial disparities and ways to address them.
"Multiplex immunohistochemistry elucidates increased distance between cytotoxic T cells and plasma cells in relapsed myeloma, and identifies Lag-3 as the most common checkpoint receptor on cytotoxic T cells of myeloma patients"
Source
Ninkovic S, Purton LE, Harrison SJ, Quach H. Multiplex immunohistochemistry elucidates increased distance between cytotoxic T cells and plasma cells in relapsed myeloma, and identifies Lag-3 as the most common checkpoint receptor on cytotoxic T cells of myeloma patients. Haematologica 2024;109(5):1487-1500; https://doi.org/10.3324/haematol.2023.283344.
Overview
With multiple myeloma, the immune system does not work properly, allowing the cancer to grow. Researchers used a special staining technique to study the immune cells called T cells in bone marrow samples from patients with different stages of MM.
They looked at cytotoxic T cells, which can kill cancer cells, and measured how close these T cells were to the myeloma cancer cells. They compared newly diagnosed MM patients to those with relapsed or hard-to-treat MM.
The researchers found that in newly diagnosed patients, a higher percentage of the cytotoxic T cells were located close to the cancer cells compared to relapsed patients. This suggests the T cells may be better able to fight the cancer early on.
They also looked at certain proteins (checkpoint receptors) on the T cells that can prevent them from attacking cancer effectively. The Lag-3 protein was most common on the cytotoxic T cells in myeloma patients.
This study is the first to examine how close T cells are to myeloma cells in actual bone marrow samples. The findings support using new immunotherapies earlier in treatment that can help the T cells better recognize and kill the cancer cells.
"Pharmacologic targeting of the p62 ZZ domain enhances both anti-tumor and bone-anabolic effects of bortezomib in multiple myeloma"
Source
Marino S, Petrusca DN, Bishop RT, Anderson JL, Sabol HM, Ashby C, Layer JH, Cesarano A, Davé UP, Perna F, Delgado-Calle J, Chirgwin JM, Roodman GD. Pharmacologic targeting of the p62 ZZ domain enhances both anti-tumor and bone-anabolic effects of bortezomib in multiple myeloma. Haematologica 2024;109(5):1501-1513; https://doi.org/10.3324/haematol.2023.283787.
Overview
Researchers tested a drug called XRK3F2 that binds to p62. They found that giving XRK3F2 along with bortezomib had two major benefits:
- It increased killing of the multiple myeloma cancer cells through two different cell death processes called apoptosis and necroptosis.
- It helped preserve bone mass by allowing more new bone-building cells (osteoblasts) while blocking bone destruction by other cells (osteoclasts).
In experiments with human multiple myeloma cells and in mice with the cancer, using XRK3F2 and bortezomib together worked better than either drug alone at reducing tumor burden and preventing bone damage from the cancer.
The researchers suggest that drugs targeting p62, combined with proteasome inhibitors, could improve treatment for multiple myeloma by better killing the cancer cells and protecting bone health.
"Factors associated with refractoriness or early progression after idecabtagene vicleucel in patients with relapsed/ refractory multiple myeloma: US Myeloma Immunotherapy Consortium real world experience. "Pharmacologic targeting of the p62 ZZ domain enhances both anti-tumor and bone-anabolic effects of bortezomib in multiple myeloma"
Source
Hashmi H, Hansen DK, Peres LC, Puglianini OC, Freeman C, De Avila G, Sidana S, Shune L, Sborov DW, Davis J, Wagner C, Kocoglu MH, Atrash S, Voorhees P, Simmons G, Ferreri C, Kalariya N, Anderson Jr. LD, Afrough A, Dima D, Khouri J, McGuirk J, Locke F, Baz R, Patel KK, Alsina M. Factors associated with refractoriness or early progression after idecabtagene vicleucel in patients with relapsed/ refractory multiple myeloma: US Myeloma Immunotherapy Consortium real world experience. Haematologica 2024;109(5):1514-1524
Overview
Idecabtagene vicleucel (ide-cel) is a promising CAR T-cell therapy for treating multiple myeloma. Yet, some patients do not respond well or relapse quickly after receiving this treatment.
Researchers looked at data from 211 multiple myeloma patients treated with the standard ide-cel CAR T-cell therapy across 11 cancer centers in the U.S. They wanted to understand what factors were associated with patients progressing (their cancer getting worse) or dying within the first 3 months after the CAR T-cell infusion.
They found that patients with the following characteristics were more likely to have early progression within 3 months:
- Prior spread of the cancer outside the bone marrow
- Previous treatment with other BCMA-targeted therapies
- High ferritin levels before lymphodepletion (prep for CAR T-cells)
- Needing bridging therapy to control the cancer before CAR T-cells
- Being Hispanic
- Having plasma cell leukemia
- Having the t(4;14) genetic abnormality
Of these risk factors, having prior spread outside the marrow, previous BCMA therapy, high ferritin, plasma cell leukemia, and t(4;14) were linked to worse progression-free survival in additional analysis.
Patients with 3 or more of these high-risk factors had very poor outcomes, with their cancer typically progressing again by 3.2 months after CAR T-cell therapy.
The researchers say identifying these high-risk patients early could allow for additional treatments before or after CAR T-cells to potentially improve their outcomes.
"Use of the Second Revision of the International Staging System for prognostic stratification of multiple myeloma patients in real-world clinical practice and the importance of sub-groups, including age "
Source
Uesugi Y, Ikeda D, Fukumoto A, Tabata R, Miura D, Narita K, Takeuchi M, Matsue K. Use of the Second Revision of the International Staging System for prognostic stratification of multiple myeloma patients in real-world clinical practice and the importance of sub-groups, including age. Haematologica 2024;109(5):1593-1597; https://doi.org/10.3324/haematol.2023.284173
Overview
Researchers looked at the Second Revision of the Revised International Staging System (R2-ISS) for multiple myeloma.This system further divides patients into risk groups by checking for an abnormality called gain of 1q using a test called fluorescence in situ hybridization (FISH).
The researchers reviewed data from 218 multiple myeloma patients diagnosed at their cancer center in Japan between 2014-2022. They followed proper ethical standards and had approval to analyze patient information.
In analyzing their patient data using the R2-ISS staging, the researchers found that factors like patient age may impact how useful clinical trial findings are when applied to real-world patients seen in regular clinical practice.
Many clinical trials have strict rules for who can participate, often excluding older or frailer patients. However, as the population ages, there are more of these older patient groups that need to be accounted for.
The researchers emphasize that doctors should consider patient factors like age when looking at data from clinical trials and staging systems like R2-ISS. Tailoring cancer care based on an individual's situation, beyond just staging system results, may help further improve treatment outcomes.
Insight from additional analyses of real-world patients can complement findings from clinical trials when making decisions about the best care approach for each multiple myeloma patient.
"A prospective, multicenter study on hematopoietic stem cell mobilization with cyclophosphamide plus granulocyte colony-stimulating factor and ‘on-demand’ plerixafor in multiple myeloma patients treated with novel agents"
Source
Mina R, Petrucci MT, Bonello F, Bongarzoni V, Saccardi R, Bertuglia G, Mengarelli A, Spadaro A, Lisi C, Curci P, Lemoli RM, Ballanti S, Floris R, Cupelli L, Tosi P, Olivieri A, Rota-Scalabrini D, Cangialosi C, Nozzoli C, Anaclerico B, Fazio F, Bruno B, Mancuso K, Corradini P, Milone G, Boccadoro M. A prospective, multicenter study on hematopoietic stemcell mobilization with cyclophosphamide plus granulocyte colony-stimulating factor and ‘on-demand’ plerixafor in multiple myeloma patients treated with novel agents. Haematologica 2024;109(5):1525-1534; https://doi.org/10.3324/haematol.2023.284023
Overview
For patients with newly diagnosed multiple myeloma who are eligible for a stem cell transplant, collecting enough hematopoietic stem cells (HSCs) is crucial. This allows the patient's blood counts to recover after the high-dose chemotherapy given as part of the transplant.
In this study, researchers evaluated a mobilization strategy to collect HSCs from 301 newly diagnosed multiple myeloma patients treated with novel drug therapies as their initial treatment. The mobilization used G-CSF, cyclophosphamide, and the drug plerixafor "on-demand" for patients struggling to mobilize stem cells.
The main objective was to see how many patients were "poor mobilizers" - collecting less than 2 million HSCs per kg body weight or needing plerixafor rescue to get an adequate collection.
Overall, 95% of patients collected at least 2 million HSCs/kg, with a median of 9.9 million collected. However, 16% were poor mobilizers - 11% needed plerixafor and 5% failed collection despite plerixafor.
For those given plerixafor, 90% were then able to collect over 2 million HSCs/kg.
Certain factors increased the risk of mobilization failure or needing plerixafor rescue: over 60% plasma cells in the bone marrow at diagnosis, prior lenalidomide treatment, and severe blood count problems during initial therapy.
The researchers concluded this mobilization approach using plerixafor as needed was effective for newly diagnosed myeloma patients, resulting in a high stem cell collection rate and yield after novel drug induction therapy.
"Minimal Residual Disease Status in Multiple Myeloma 1 Year After Autologous Hematopoietic Cell Transplantation and Lenalidomide Maintenance Are Associated With Long-Term Overall Survival"
Source
Marcelo C. Pasquini et al. Minimal Residual Disease Status in Multiple Myeloma 1 Year After Autologous Hematopoietic Cell Transplantation and Lenalidomide Maintenance Are Associated With Long-Term Overall Survival. JCO 0, JCO.23.00934. DOI:10.1200/JCO.23.00934. Accessed May 3, 2024.
Overview
The Prognostic Immunophenotyping in Myeloma Response (PRIMeR) study looked at minimal residual disease (MRD) in multiple myeloma patients. The patients were part of a clinical trial testing different treatments for multiple myeloma. The study used a special type of flow cytometry to measure MRD levels in 435 patients at different time points: before stem cell transplant, before maintenance therapy, and one year after transplant.
The main goal was to see if having no measurable MRD one year after transplant predicted better outcomes. The results showed that patients with no MRD at any time point had significantly better progression-free survival. Having no MRD one year after transplant also predicted better overall survival. Patients who had no MRD throughout or became MRD negative by one year had similar good outcomes. This study provides evidence that measuring MRD can help predict long-term outcomes and guide future trials to improve progression-free and overall survival in multiple myeloma.
"An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis"
Source
Pereira, R.; Bergantim, R. An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis. Int. J. Mol. Sci. 2024, 25, 4996. https://doi.org/10.3390/ijms25094996
Overview
Researchers looked at many studies on CAR-T cell therapy for multiple myeloma patients whose myeloma relapsed after other treatments. They found 29 studies that fit their criteria.
The studies showed that CAR-T cell therapy worked well for these patients. Around 83 out of 100 patients responded to treatment for a while.
Overall, CAR-T cell therapy seemed safe. Only around 7 out of 100 patients had serious side effects like an overactive immune system response. Around 1 out of 100 had serious nerve-related side effects.
Patients who received fewer treatments before CAR-T responded better. Patients with higher-risk cancer features or previous CAR-T exposure were more likely to have the overactive immune response side effect.
This new CAR-T therapy could help many multiple myeloma patients when other treatments stop working. While it has some risks, it seems effective and generally safe based on the evidence so far.
"Detection of clonal plasma cells in POEMS syndrome using multiparameter flow cytometry"
Source
Ishii, A., Tsukamoto, S., Mimura, N. et al. Detection of clonal plasma cells in POEMS syndrome using multiparameter flow cytometry. Sci Rep 14, 10362 (2024). https://doi.org/10.1038/s41598-024-61034-1 Accessed May 6, 2024.
Overview
From the study: "This study evaluated the sensitivity of EuroFlow-NGF [next-generation flow]-based MFC [multipareter flow cytometry] in detecting clonal plasma cells [PCs] in POEMS syndrome and demonstrated the usefulness of the optimized POEMS-flow, gating CD38 broadly from dim to bright and CD45 narrowly from negative to dim compared to EuroFlow-NGF-based MFC. This strategy needs to be validated in a larger cohort. This preliminary data indicates that POEMS-flow could improve the identification rate of monoclonal PCs in POEMS syndrome and become a valuable tool for diagnosing POEMS syndrome."
"Mass Spectrometry-Based Assessment of M-protein in Peripheral Blood During Maintenance Therapy in Multiple Myeloma"Detection of clonal plasma cells in POEMS syndrome using multiparameter flow cytometry"
Source
Tadeusz Kubicki, Dominik Dytfeld, David R. Barnidge, Dhananjay Sakrikar, Anna Przybyłowicz-Chalecka, Krzysztof Jamroziak, Pawel Robak, Jaroslaw Czyz, Agata Tyczynska, Agnieszka Agata Druzd-Sitek, Krzysztof Giannopoulos, Tomasz Wróbel, Adam Nowicki, Tomasz Szczepaniak, Anna Łojko-Dankowska, Magdalena Matuszak, Lidia Anna Gil, Bartosz Puła, Lukasz Szukalski, Agnieszka Końska, Jan Maciej Zaucha, Jan Walewski, Damian Mikulski, Olga Czabak, Tadeusz Robak, Ken Jiang, Jennifer Helen Cooperrider, Andrzej J Jakubowiak, Benjamin A. Derman; Mass Spectrometry-Based Assessment of M-protein in Peripheral Blood During Maintenance Therapy in Multiple Myeloma. Blood 2024; blood.2024024041. doi: https://doi.org/10.1182/blood.2024024041. Accessed May 7, 2024
Overview
Key points from the study:
- "Mass spectrometry provides significant prognostic information in the maintenance setting and complements bone marrow MRD in multiple myeloma.
- Without a baseline serum sample, mass spectrometry's prognostic performance is most significant after 18 months post-transplant."
"A research center's experience of T-cell redirecting therapies in triple-class refractory multiple myeloma"
Source
Borja Puertas, Adolfo Fernández-Sánchez, Elena Alejo, Beatriz Rey-Bua, Ana África Martín-López, Estefaía Pérez López, Miriam Lopez-Parra, Lucia Lopez-Corral, Norma C. Gutierrez, Ramón García-Sanz, Noemi Puig, Veronica Gonzalez-Calle, Maria-Victoria Mateos; A research center's experience of T-cell redirecting therapies in triple-class refractory multiple myeloma. Blood Adv 2024; bloodadvances.2024012773. doi: https://doi.org/10.1182/bloodadvances.2024012773 Accessed May 8, 2024
Overview
Key points from the study:
- "CAR-T resulted stronger responses than bispecific antibodies (BiAbs) but lacked clinical significance in the case of PFS.
- CAR-T followed by BiAbs could be one of the best treatment sequences for managing triple-class refractory myeloma."
"Target trial emulation of carfilzomib safety among patients with relapsed/refractory multiple myeloma using a nationwide observational data in Korea. Journal of Cancer Research and Clinical Oncology"
Source
Hyun Kyung Lee, Ha Young Jang, In‐Wha Kim, and Jung Mi Oh.Target trial emulation of carfilzomib safety among patients with relapsed/refractory multiple myeloma using a nationwide observational data in Korea. Journal of Cancer Research and Clinical Oncology (2024) 150:266 https://doi.org/10.1007/s00432-024-05800-8 Accessed May 10, 2024
Overview
The researchers wanted to look at the safety of the drug carflzomib when used to treat multiple myeloma patients whose cancer had returned or stopped responding to treatment. Carflzomib is often used for this purpose, but its approval was fast-tracked, so more real-world safety data was needed, especially in diverse populations.
They compared new users of the carflzomib combination treatment (called KRd) to those getting a different combination treatment (called Rd) using a national database of medical claims in Korea. The study included 4,580 multiple myeloma patients from 2007 to 2020.
Compared to Rd, the KRd group had significantly higher risks of blood-related side effects like anemia, low white blood cells, and low platelets. They also had more non-blood-related side effects like cough, low potassium, constipation, high blood pressure, and heart failure.
Of the non-blood side effects, cardiovascular issues like heart failure and high blood pressure had the highest increased risk with KRd.
In summary, the safety profile of carflzomib in Korean patients was similar to previous clinical trials. But caution is still advised when using carflzomib in Asian multiple myeloma patients because of the increased cardiovascular risks.
"Antigen escape as a shared mechanism of resistance to BCMA-directed therapies in multiple myeloma"
Source
Ross S. Firestone, Nicholas D Socci, Tala Shekarkhand, Menglei Zhu, Wei Ge Qin, Malin L. Hultcrantz, Sham Mailankody, Carlyn Rose Tan, Neha Korde, Alexander M. Lesokhin, Hani Hassoun, Urvi A. Shah, Kylee H. Maclachlan, Sridevi Rajeeve, Heather J. Landau, Michael Scordo, Gunjan L Shah, Oscar B Lahoud, Sergio A Giralt, Kazunori Murata, Saad Z Usmani, David J. Chung; Antigen escape as a shared mechanism of resistance to BCMA-directed therapies in multiple myeloma. Blood 2024; blood.2023023557. doi: https://doi.org/10.1182/blood.2023023557 Accessed May 10, 2024
Overview
Key points from the study:
- "Therapy-mediated loss of BCMA expression after belantamab mafodotin or anti-BCMA CAR T cells underlies teclistamab failure in RRMM.
- Low/undetectable peripheral blood soluble BCMA reflects loss of BCMA expression by bone marrow plasma cells."
"The biological and clinical impact of deletions before and after large chromosomal gains in multiple myeloma"
Source
Anthony M. Cirrincione, Alexandra M Poos, Bachisio Ziccheddu, Marcella Kaddoura, Marc-Andrea Baertsch, Kylee H. Maclachlan, Monika Chojnacka, Benjamin T. Diamond, Lukas John, Philipp Reichert, Stefanie Huhn, Patrick Blaney, Dylan C Gagler, Karsten Rippe, Yanming Zhang, Ahmet Dogan, Alexander M. Lesokhin, Faith E Davies, Hartmut Goldschmidt, Roland Fenk, Katja C. Weisel, Elias K Mai, Neha Korde, Gareth J Morgan, Saad Z Usmani, Ola Landgren, Marc S. Raab, Niels Weinhold, Francesco Maura; The biological and clinical impact of deletions before and after large chromosomal gains in multiple myeloma. Blood 2024; blood.2024024299. doi: https://doi.org/10.1182/blood.2024024299 Accessed May 10, 2024
Overview
Key points from the study:
- "Hyperdiploid, historically considered an initiating event in multiple myeloma, can be preceded by deletions involving driver genes.
- Deletions within large chromosomal gains represent a novel mechanism that impacts both driver gene expression and clinical outcome."
"International Myeloma Working Group immunotherapy committee consensus guidelines and recommendations for optimal use of T-cell-engaging bispecific antibodies in multiple myeloma"
Source
Rodriguez-Otero, P., Usmani, S., et al. International Myeloma Working Group immunotherapy committee consensus guidelines and recommendations for optimal use of T-cell-engaging bispecific antibodies in multiple myeloma. The Lancet Oncology. Vol. 25, Issue 5, E205-E216. doi:https://doi.org/10.1016/S1470-2045(24)00043-3 Accessed May 16, 2024
Overview
Multiple myeloma remains incurable, despite many new drug treatments that have helped patients live longer. Recently, new immunotherapies that use the body's immune system to fight the cancer cells have been approved and shown very promising results.
These immunotherapies work differently than previous myeloma treatments and can cause different side effects. Because they are so new, doctors need guidance on how to properly manage patients receiving these therapies based on experiences from clinical trials.
This article provides expert consensus guidelines for using a specific type of immunotherapy called bispecific antibodies to treat multiple myeloma. The International Myeloma Working Group is also collecting data from patients receiving these new immunotherapies. The goal is to continuously learn and improve how doctors manage patients getting these pioneering cancer treatments.
New immunotherapy drugs are a major advance in the treatment of multiple myeloma, but doctors need guidance tailored to these treatments' unique effects so patients receive optimal care as usage expands worldwide.
"Bone marrow stromal cells induce chromatin remodeling in multiple myeloma cells leading to transcriptional changes"
Source
Binder, M., Szalat, R.E., Talluri, S. et al. Bone marrow stromal cells induce chromatin remodeling in multiple myeloma cells leading to transcriptional changes. Nat Commun 15, 4139 (2024). https://doi.org/10.1038/s41467-024-47793-5 Accessed May 16, 2024
Overview
Multiple myeloma is a cancer of the bone marrow. Normally, the bone marrow provides support for the myeloma cancer cells to grow and become resistant to treatments.
In this study, the researchers looked at how the bone marrow cells interact with myeloma cells from human cell lines. They found that this interaction changes the myeloma cells' genes related to cell movement and communication with other cells.
The same gene changes were seen in myeloma patients whose cancer had spread outside the bone marrow. This suggests these gene changes help myeloma cells survive outside the bone marrow environment.
Some newly diagnosed myeloma patients already had these gene changes. In those patients, the cancer spread faster, became treatment resistant sooner, and they had worse outcomes overall.
The researchers conclude that the bone marrow interactions cause genetic and epigenetic changes that predict how aggressive a patient's myeloma will be. Targeting these interactions could lead to new myeloma treatments.
"1q amplification and PHF19 expressing high-risk cells are associated with relapsed/refractory multiple myeloma"
Source
Johnson, T.S., Sudha, P., Liu, E. et al. 1q amplification and PHF19 expressing high-risk cells are associated with relapsed/refractory multiple myeloma. Nat Commun 15, 4144 (2024). https://doi.org/10.1038/s41467-024-48327-9 Accessed May 16, 2024
Overview
Multiple myeloma affects plasma cells, which are cells that make antibodies. The cancerous plasma cells quickly become resistant to the standard treatments like immunomodulatory drugs and proteasome inhibitors. This causes the cancer to progress.
Researchers can look at the DNA and RNA of myeloma cells to find markers that indicate a high risk of the cancer progressing after treatment. One of these markers is the gene PHF19, which controls the cell cycle and other processes.
In this study, the researchers analyzed DNA, RNA, and other data from over 325,000 myeloma cells from 49 patients. They identified a subtype of plasma cells associated with myeloma progression that they called relapsed/refractory plasma cells (RRPCs). These cells had alterations in chromosome 1q, mutations in the TP53 gene, and high expression of PHF19.
The researchers found that in RRPCs, cell cycle inhibitors were dysregulated, possibly controlled by the transcription factor PBX1 on chromosome 1q. They determined that PHF19 may act primarily through this subset of relapsed/refractory plasma cells to drive myeloma progression.
"How can we stamp out high-risk myeloma?"
Source
Rahul Banerjee, Joseph R. Mikhael; How can we stamp out high-risk myeloma?. Blood 2024; 143 (20): 2015–2016. doi: https://doi.org/10.1182/blood.2024024140 Accessed May 16, 2024
Overview
The study by Touzeau et al in Blood reports on the phase 2 IFM 2018-04 trial testing quadruplet induction therapy (daratumumab, carfilzomib, lenalidomide, dexamethasone) followed by double autologous stem cell transplant (ASCT) and maintenance therapy in patients with high-risk multiple myeloma. Key findings include:
- 36 out of 50 patients received both planned stem cell transplants after induction
- 2-year progression-free survival was 80-85%
- Infections like COVID-19 were common adverse events
The authors discuss how this approach using more intensive treatment for longer duration may improve outcomes in high-risk disease compared to standard therapy. They compare it to other recent trials like MASTER, GMMG-CONCEPT, and MUKnine that also used multi-drug induction and transplant in high-risk myeloma.
Potential challenges highlighted include ensuring adequate stem cell collection during quadruplet induction therapy. The authors raise questions around ideal induction regimen, role of double vs single transplant, and optimal maintenance therapy duration and drugs.
Overall, the study adds another intensive treatment paradigm showing promising outcomes in high-risk myeloma. However, many questions remain on best way to manage these higher-risk patients long-term.
"Smoldering multiple myeloma: taking the narrow over the wide path?"
Source
Herve Avet-Loiseau, Nizar J. Bahlis; Smoldering multiple myeloma: taking the narrow over the wide path?. Blood 2024; 143 (20): 2025–2028. doi: https://doi.org/10.1182/blood.2024023880 Accessed May 16, 2024
Overview
Some researchers have suggested doing medical interventions or treatments on smoldering multiple myeloma patients, even though their condition is not causing any issues currently. However, the abstract argues that this may actually be harmful.
Instead, the authors recommend closely monitoring smoldering multiple myeloma patients over time without any treatments. They suggest enrolling these patients in observational studies to better understand the biology of their abnormal plasma cells, including things like genetics, epigenetics, and the immune environment. This could help identify which patients are most likely to develop active multiple myeloma, so treatments can be considered at that point.
The main point is that treating smoldering multiple myeloma prematurely with interventions may do more harm than good. Careful monitoring and biological studies are favored over aggressive upfront treatments for this pre-cancerous condition.
"Data mining for second malignancies after CAR-T"
Source
Helen E. Heslop; Data mining for second malignancies after CAR-T. Blood 2024; 143 (20): 2023–2024. doi: https://doi.org/10.1182/blood.2024024446 Accessed May 16, 2024
Overview
This article in the journal Blood discusses a study by Elsallab et al. that looked at reports of second primary cancers after treatment with FDA-approved CAR-T cell therapies. CAR-T cell therapy is a type of cancer treatment that uses genetically engineered T cells to target cancer cells.
The study analyzed data from the FDA's database of adverse event reports (FAERS). Out of over 12,000 adverse events reported after CAR-T therapy, 536 (4.3%) were second primary cancers. Myeloid cancers like acute myeloid leukemia and myelodysplasia were most common. There were also 19 cases of T-cell cancers reported.
The FDA had previously announced an investigation into a potential risk of T-cell cancers after CAR-T therapy, as the CAR gene was detected in some T-cell cancer cases. However, other studies have not found an increased risk so far.
Patients receiving CAR-T therapy often have other risk factors for second cancers, like previous treatments and genetic mutations. The FAERS data has limitations in estimating true cancer risk.
While very effective, long-term monitoring of CAR-T recipients is important to understand the full risks. Enrolling patients in registries can help gather more complete data on second cancer rates compared to adverse event reports alone.
Overall, the benefits of CAR-T therapy still appear to outweigh the potential risks based on current knowledge. But continued study and patient follow-up is needed.
"Daratumumab, carfilzomib, lenalidomide, and dexamethasone with tandem transplant for high-risk newly diagnosed myeloma"
Source
Cyrille Touzeau, Aurore Perrot, Cyrille Hulin, Salomon Manier, Margaret Macro, Marie-Lorraine Chretien, Lionel Karlin, Martine Escoffre, Caroline Jacquet, Mourad Tiab, Xavier Leleu, Herve Avet-Loiseau, Alexandra Jobert, Lucie Planche, Jill Corre, Philippe Moreau; Daratumumab, carfilzomib, lenalidomide, and dexamethasone with tandem transplant for high-risk newly diagnosed myeloma. Blood 2024; 143 (20): 2029–2036. doi: https://doi.org/10.1182/blood.2023023597 Accessed May 16, 2024
Overview
Key points from the study:
- "Darzalex (daratumumab), Kyprolis (carfilzomib), and dexamethasone (KRd) induction and consolidation with double transplant is feasible in high-risk, transplant-eligible, newly diagnosed multiple myeloma.
- D-KRd with double transplant result in high rates of MRD negativity, progression-free survival, and overall survival in high-risk multiple myeloma."
"Second primary malignancies after commercial CAR T-cell therapy: analysis of the FDA Adverse Events Reporting System"
Source
Magdi Elsallab, Moataz Ellithi, Matthew A. Lunning, Christopher D’Angelo, Jihyun Ma, Miguel-Angel Perales, Matthew Frigault, Marcela V. Maus; Second primary malignancies after commercial CAR T-cell therapy: analysis of the FDA Adverse Events Reporting System. Blood 2024; 143 (20): 2099–2105. doi: https://doi.org/10.1182/blood.2024024166 Accessed May 16, 2024
Overview
From the study:
"Second primary malignancies were reported in 536 of 12 394 (4.3%) adverse event reports following chimeric antigen receptor T-cell therapies in the Food and Drug Administration Adverse Event Reporting System. Myeloid and T-cell neoplasms were disproportionately more frequently reported, warranting further follow-up."
"Clinical evaluation and determinants of response to HBI0101 (BCMA CART) therapy in relapsed/refractory multiple myeloma"
Source
Shlomit Kfir-Erenfeld, Nathalie Asherie, Eyal Lebel, Vladimir Vainstein, Miri Assayag, Tatyana Dubnikov Sharon, Sigal Grisariu, Batia Avni, Shlomo Elias, Rivka Alexander-Shani, Nomi Bessig, Alaa Shehadeh, Aseel Ishtay, Veronica Zelmanovich, Eran Zimran, Marjorie Pick, Ilan Roziner, Ron S. Kenett, Yael C. Cohen, Irit Avivi, Cyrille J. Cohen, Moshe E. E Gatt, Polina Stepensky; Clinical evaluation and determinants of response to HBI0101 (BCMA CART) therapy in relapsed/refractory multiple myeloma. Blood Adv 2024; bloodadvances.2024012967. doi: https://doi.org/10.1182/bloodadvances.2024012967 Accessed May 20, 2024
Overview
Key points frrom the study:
- "HBI0101, an academic BCMA CART therapy for multiple myeloma, is a safe, efficient and available local alternative to commercial drugs.
- High-risk cytogenetic, extramedullary disease and CART differentiation status are predictors of HBI0101 response durability."
"Multiple myeloma patients with a long remission after autologous hematopoietic stem cell transplantation"
Source
Magdi Elsallab, Moataz Ellithi, Matthew A. Lunning, Christopher D’Angelo, Jihyun Ma, Miguel-Angel Perales, Matthew Frigault, Marcela V. Maus; Second primary malignancies after commercial CAR T-cell therapy: analysis of the FDA Adverse Events Reporting System. Blood 2024; 143 (20): 2099–2105. doi: https://doi.org/10.1038/s41408-024-01062-2 Accessed May 16, 2024
Overview
From the study:
"Second primary malignancies were reported in 536 of 12 394 (4.3%) adverse event reports following chimeric antigen receptor T-cell therapies in the Food and Drug Administration Adverse Event Reporting System. Myeloid and T-cell neoplasms were disproportionately more frequently reported, warranting further follow-up."
"EVIDENCE meta-analysis: evaluating minimal residual disease as an intermediate clinical endpoint for multiple myeloma"
Source
Ola Landgren, Thomas J Prior, Tara Masterson, Christoph Heuck, Orlando F Bueno, Ajeeta B. Dash, Hermann Einsele, Hartmut Goldschmidt, Stefan Knop, Cong Li, Ulf-Henrik Mellqvist, Ian McFadden, Corina Oprea, Jeremy A Ross, Mihaela Talpes, Jay Hydren, Jenny Ahlstrom, Dickran Kazandjian, Rick Zhang, Gerald E Marti, Sean M. Devlin, Niels Weinhold, Maryalice Stetler-Stevenson; EVIDENCE meta-analysis: evaluating minimal residual disease as an intermediate clinical endpoint for multiple myeloma. Blood 2024; blood.2024024371. doi: https://doi.org/10.1182/blood.2024024371 Accessed May 20, 2024
Overview
Key points from the study:
- "MRD-negativity at 12 months reduced the risk of progression; the treatment effect on MRD was correlated with the treatment effect on progression-free survival (PFS).
- MRD negativity is reasonably likely to eventually demonstrate a treatment effect on PFS."
"Immune status and selection of patients for immunotherapy in myeloma: a proposal"
Source
Madhav V. Dhodapkar; Immune status and selection of patients for immunotherapy in myeloma: a proposal. Blood Adv 2024; 8 (10): 2424–2432. doi: https://doi.org/10.1182/bloodadvances.2023011242 Accessed on May 28, 2024
Overview
New treatments for multiple myeloma use the body's own immune system to fight the cancer cells. Things like CAR-T cell therapy and bispecific antibodies are transforming how we treat this disease.
Researchers are realizing that the immune system itself plays a big role in how well other myeloma therapies work. People with myeloma have immune system changes that start early on when the cancer is developing. The immune environment around the tumor is also different.
Studies show that the state of a patient's immune system before and after treatment can affect how well they respond, including to the new immunotherapies. Whether their immune system is suppressed, excluded from the tumor, resistant to therapy, etc. seems to matter.
Myeloma is a cancer that spreads to many sites in the body. Just like solid tumors, considering the immune landscape in each of those tumor sites may be key for getting the most benefit from immunotherapies like CAR-T cells.
The researchers propose five distinct "immune types" of myeloma based on the spatial immune patterns. Using a classification like this could help doctors select the optimal immunotherapy for each patient to improve outcomes.
"Treg-derived TGF-β1 dampens cGAS-STING signaling to downregulate the expression of class I MHC complex in multiple myeloma"
Source
Zhang, D., Zhan, D., Zhang, R. et al. Treg-derived TGF-β1 dampens cGAS-STING signaling to downregulate the expression of class I MHC complex in multiple myeloma. Sci Rep 14, 11593 (2024). https://doi.org/10.1038/s41598-024-62298-3 Accessed May 21, 2024
Overview
In multiple myeloma (MM), the tumor cells don't show enough antigens (molecules that allow the immune system to recognize them as foreign) on their surface. This is because MM tumor cells have low levels of MHC class I molecules and high levels of PDL1 (a protein that suppresses immune responses). MM also has a lot of regulatory T cells (Tregs) which suppress the immune system.
The researchers set up experiments growing MM tumor cells together with Tregs from MM patients. They found that the Tregs made the tumor cells produce more TGF-β1 (a protein that helps tumors grow). TGF-β1 reduced MHC class I levels and increased PDL1 levels on the tumor cells by blocking the cGAS-STING pathway (an immune pathway).
When the researchers blocked TGF-β1 or activated the cGAS-STING pathway in mice with MM, it restored MHC I and reduced PDL1 on the tumor cells. This overcame the tumor-promoting effects of Tregs.
Tregs help MM tumors escape the immune system by increasing TGF-β1. Blocking TGF-β1 or activating cGAS-STING could be new treatment approaches by allowing the immune system to better recognize and attack the tumor cells.
"Pharmacodynamic changes in tumor and immune cells drive iberdomide’s clinical mechanisms of activity in relapsed and refractory multiple myeloma"
Source
Michael Amatangelo, Erin Flynt, Nicholas Stong, Pradipta Ray, Oliver Van Oekelen, Maria Wang, Maria Ortiz, Paulo Maciag, Teresa Peluso, Samir Parekh, Niels W.C.J. van de Donk, Sagar Lonial, Anjan Thakurta. Pharmacodynamic changes in tumor and immune cells drive iberdomide’s clinical mechanisms of activity in relapsed and refractory multiple myeloma. Cell Reports Medicine, 2024, 101571, ISSN 2666-3791, https://doi.org/10.1016/j.xcrm.2024.101571. Accessed May 21, 2024.
Overview
Key points from the study:
"Iberdomide:
- is pharmacodynamically active in late-line myeloma post-IMiDs.
- can overcome cereblon dysregulation associated with IMiD resistance.
- stimulates immune cell proliferation.
- shifts immunophenotype toward activated/effector memory T cells."
"Absolute Lymphocyte Count after BCMA CAR-T Therapy is a Predictor of Response and Outcomes in Relapsed Multiple Myeloma"
Source
Mateo Mejia Saldarriaga, Darren Pan, Caitlin Unkenholz, Tarek H Mouhieddine, Juan Esteban Velez-Hernandez, Katherine Engles, Joshua Alexander Fein, Jorge Monge, Cara A Rosenbaum, Roger Pearse, David S. Jayabalan, Christian A Gordillo, Hei Ton Chan, Samuel Yamshon, Santiago Thibaud, Markus Y Mapara, Giorgio GA Inghirami, Suzanne Lentzsch, Ran Reshef, Adriana Rossi, Samir Parekh, Sundar Jagannath, Shambavi Richard, Ruben Niesvizky, Mark Bustoros; Absolute Lymphocyte Count after BCMA CAR-T Therapy is a Predictor of Response and Outcomes in Relapsed Multiple Myeloma. Blood Adv 2024; bloodadvances.2023012470. doi: https://doi.org/10.1182/bloodadvances.2023012470 Accessed May 22, 2024
Overview
Key points from the study:
- "Maximum absolute lymphocyte count (ALCmax) in the first 15 days after BCMA CAR-T cell infusion is associated with deeper response and occurrence of cytokine release syndrome (CRS) and ICANS.
- ALCmax less than 0.5 x103/uL is predictive of non-responders, while that >1.0 is an independent prognostic biomarker for sustained response."
"Proposal for harmonizing the reporting of infections during treatment with bispecific antibodies in multiple myeloma"
Source
Heinz Ludwig, Nikhil C. Munshi, Evangelos Terpos, Ilvy Schweitzer, Noopur Raje, Philippe Moreau, Ajay K. Nooka; Proposal for harmonizing the reporting of infections during treatment with bispecific antibodies in multiple myeloma. Blood Adv 2024; bloodadvances.2024013461. doi: https://doi.org/10.1182/bloodadvances.2024013461 Accessed May 22, 2024
Overview
Researchers looked at medical records to understand the early signs and symptoms of a disease called AL amyloidosis before patients were diagnosed. This disease affects multiple organs in the body.
The study included 1,401 patients diagnosed with AL amyloidosis between 2015-2020. Their medical records from the 3 years before diagnosis were examined. The patients were diverse, including 46% females, 16% non-Hispanic Black, and 6% Hispanic. The median age was 71 years old.
The researchers identified 19 potential early conditions or symptoms that could be warning signs of AL amyloidosis, such as shortness of breath, fatigue, weight loss, and edema (swelling). On average, patients had 5 of these early conditions recorded before diagnosis.
The time from when the first potential warning sign appeared to when AL amyloidosis was diagnosed ranged from 3.2 to 21.4 months, depending on the condition. Many of the early conditions tended to occur together.
This information about the timing and patterns of early symptoms could help create methods to identify AL amyloidosis sooner before multiple organs are affected. Catching the disease earlier may improve outcomes.
"Prognostic impact of corticosteroid and tocilizumab use following chimeric antigen receptor T-cell therapy for multiple myeloma"
Source
Costa, B.A., Flynn, J., Nishimura, N. et al. Prognostic impact of corticosteroid and tocilizumab use following chimeric antigen receptor T-cell therapy for multiple myeloma. Blood Cancer J. 14, 84 (2024). https://doi.org/10.1038/s41408-024-01048-0 Accessed May 27, 2024
Overview
Researchers looked at how drugs used to treat side effects from CAR T-cell therapy affected treatment outcomes in multiple myeloma patients. CAR T-cell therapy can cause cytokine release syndrome (CRS) and neurological problems. Tocilizumab and corticosteroids are often given to manage these side effects.
The study included 101 multiple myeloma patients who received CAR T-cell therapy targeting the BCMA or GPRC5D proteins. Within 30 days after treatment, 34% were given corticosteroids and 49% received tocilizumab for CRS or neurological issues.
After following patients for over 2 years on average, the researchers found no significant difference in progression-free survival between those who did or did not receive corticosteroids or tocilizumab. Response rates and overall survival were also similar in all groups.
In their analysis, using corticosteroids and/or tocilizumab to manage side effects did not independently impact how long patients remained progression-free after CAR T-cell therapy.
The findings suggest that giving these drugs appropriately to control immune-related toxicities does not seem to negatively affect the anti-cancer efficacy and long-term outcomes of CAR T-cell treatment for relapsed/refractory multiple myeloma.
"Factors determining utilization of stem cell transplant for initial therapy of multiple myeloma by patient race: exploring intra-racial healthcare disparities"
Source
Ailawadhi, S., Adu, Y., Frank, R.D. et al. Factors determining utilization of stem cell transplant for initial therapy of multiple myeloma by patient race: exploring intra-racial healthcare disparities. Blood Cancer J. 14, 86 (2024). https://doi.org/10.1038/s41408-024-01067-x Accessed May 28, 2024.
Overview
In multiple myeloma, a stem cell transplant helps control the disease and delays it from getting worse.
In the United States, stem cell transplants for multiple myeloma are being used more overall. However, there are still two main issues: 1) the treatment is not being used enough in general, and 2) there are differences in who gets the treatment based on race and ethnicity.
The researchers looked at data from nearly 112,000 multiple myeloma cases. They studied different racial and ethnic groups: non-Hispanic whites, non-Hispanic blacks, Hispanics, non-Hispanic Asians, and others. They wanted to see what sociodemographic factors affected whether patients received a stem cell transplant within each group.
Across all racial and ethnic groups, factors like age, other health problems, insurance type, whether the facility was academic or community-based, and the facility's transplant volume all impacted transplant use. Gender did not make a difference.
There were some other factors that mattered for some groups but not others. These included the following:
- year of diagnosis
- income level
- education level
- geographic location of the facility
Overall, stem cell transplants are underutilized for multiple myeloma in the U.S,, even among non-Hispanic whites. Disparities also exist for underserved racial and ethnic groups. This study identified factors contributing to disparities within each group. Solutions can now be developed to increase appropriate transplant use for all patients.
"Stromal alterations in patients with monoclonal gammopathy of undetermined significance, smoldering myeloma, and multiple myeloma"
Source
Lucienne Bogun, Annemarie Koch, Bo Scherer, Roland Fenk, Uwe Maus, Felix Bormann, Karl Köhrer, Patrick Petzsch, Thorsten Wachtmeister, Romans Zukovs, Sascha Dietrich, Rainer Haas, Thomas Schroeder, Paul Jäger, Stefanie Geyh; Stromal alterations in patients with monoclonal gammopathy of undetermined significance, smoldering myeloma, and multiple myeloma. Blood Adv 2024; 8 (10): 2575–2588. doi: https://doi.org/10.1182/bloodadvances.2023011632 Accessed May 28, 2024
Overview
Key points from the study:
- "Stromal alterations are already imprinted in patients with asymptomatic stages that further progress in patients with multiple myeloma.
- The BMP/TGF-signaling pathway can play a role in progression and may become a potential therapeutic target to prevent end-organ damage."
"Mesenchymal stem cells: paving the way for myeloma onset?"
Source
Annamaria Gulla, Mariateresa Fulciniti; Mesenchymal stem cells: paving the way for myeloma onset?. Blood Adv 2024; 8 (10): 2573–2574. doi: https://doi.org/10.1182/bloodadvances.2024012705 Accessed May 28, 2024
Overview
A recent study looked at mesenchymal stem cells (MSCs) from the bone marrow of people with different stages of multiple myeloma. Researchers found that even in the early precancerous stage called monoclonal gammopathy of undetermined significance (MGUS), the MSCs already showed problems like increased aging and reduced ability to help form new blood cells and bone.
As multiple myeloma progressed from MGUS to the smoldering and active cancer stages, these issues with the MSCs worsened. The study identified a set of 296 genes that were abnormally expressed in the MSCs across all stages of the disease. Many of these genes are involved in the BMP/TGF-beta signaling pathway, which controls how MSCs develop into different cell types like bone cells.
The dysfunctional MSCs had trouble developing into bone and cartilage cells. However, blocking the TGF-beta signaling pathway with a drug helped restore the MSCs' ability to develop into bone cells. This suggests the BMP/TGF-beta pathway plays an important role in the MSC problems seen in multiple myeloma.
While the study was small, the findings raise the possibility that abnormal MSCs and disrupted bone marrow could help initiate multiple myeloma development, rather than just being a consequence of the cancer. The altered MSCs may also create an environment that suppresses the immune system's ability to fight the cancer.
This study provides new insights into how stem cells in the bone marrow may contribute to the development and progression of multiple myeloma from its earliest stages. Understanding these bone marrow changes could lead to new ways to predict disease progression and develop treatments.
"Final analysis of a phase II trial of daratumumab, carfilzomib, lenalidomide, and dexamethasone in newly diagnosed multiple myeloma without transplant"
Source
Derman, B.A., Cooperrider, J., Rosenblatt, J. et al. Final analysis of a phase II trial of daratumumab, carfilzomib, lenalidomide, and dexamethasone in newly diagnosed multiple myeloma without transplant. Blood Cancer J. 14, 87 (2024). https://doi.org/10.1038/s41408-024-01045-3 Accessed May 29, 2024
Overview
Researchers tested a new treatment for newly diagnosed multiple myeloma (a type of blood cancer). The treatment combined four drugs: daratumumab, carfilzomib, lenalidomide, and dexamethasone. Patients received 24 cycles of this treatment without having a stem cell transplant first.
The main goal was to see how many patients achieved a stringent complete response or had very low levels of residual cancer cells (less than 1 in 100,000) after 8 cycles of treatment.
A total of 42 patients started the treatment. After 8 cycles, 75% achieved the stringent response or very low residual disease goal. This met the pre-defined threshold for the treatment to be considered effective.
The researchers also looked at lower levels of residual disease over time. More patients achieved an even deeper response as treatment continued beyond 8 cycles.
They used three different methods to measure residual disease levels. Two of the methods agreed well with each other, especially later in treatment.
With this treatment approach, 85% of patients were free of cancer progression at 3 years. 95% were still alive at 3 years. The most common side effect was upper respiratory infections. Overall, the extended treatment was effective and had acceptable safety.
"Management of complications of chimeric antigen receptor T-cell therapy: a report by the European Society of Blood and Marrow Transplantation"
Source
Penack O, Peczynski C, Boreland W, Wolff D, Moiseev I, Schoemans H, Koenecke C, Graham C, Peric Z. Management of complications of chimeric antigen receptor T-cell therapy: a report by the European Society of Blood and Marrow Transplantation. Haematologica; https://doi.org/10.3324/haematol.2023.284810 Accessed May 30, 2024
Overview
CAR-T cell therapy is a standard treatment for some blood cancers like lymphoma, multiple myeloma, and leukemia. However, this therapy is still new and evolving rapidly. There are no widely accepted guidelines on how to best manage complications from CAR-T cell treatment.
Researchers from the European Society for Blood and Marrow Transplantation (EBMT) suspected there were significant differences between European cancer centers in how they prevent, diagnose, and manage short-term and long-term side effects of CAR-T cell therapy.
To investigate this, the EBMT surveyed 227 European centers that provide CAR-T cell therapy. 106 centers (47%) fully answered the survey questions on topics like selecting the CAR-T product, logistics, managing cytokine release syndrome and neurotoxicity from the immune effects, as well as later phase management including low blood cell counts.
The survey found some common patterns but also significant variety between centers in how they clinically manage important aspects of CAR-T cell therapy. This shows a high need for more standardized treatment guidelines and future research in several key areas, including:
- Treating severe or steroid-resistant cytokine release syndrome/neurotoxicity
- Managing low blood cell counts
- Allowing early hospital discharge and outpatient management
- When to provide antibody replacement therapy
"LILRB4 represents a promising target for immunotherapy by dual targeting tumor cells and myeloid-derived suppressive cells in multiple myeloma"
Source
Gong L, Sun H, Liu L, Sun X, Fang T, Yu Z, Sui W, Xu J, Wang T, Feng F, Lei L, Rui W, Liu Y, Zhao X, An G, Lin X, Qiu L, Hao M. LILRB4 represents a promising target for immunotherapy by dual targeting tumor cells and myeloid-derived suppressive cells in multiple myeloma. Haematologica; https://doi.org/10.3324/haematol.2024.285099 Accessed May 30, 2024.
Overview
CAR-T cell therapy is a standard treatment for some blood cancers like lymphoma, multiple myeloma, and leukemia. However, this therapy is still new and evolving rapidly. There are no widely accepted guidelines on how to best manage complications from CAR-T cell treatment.
Researchers from the European Society for Blood and Marrow Transplantation (EBMT) suspected there were significant differences between European cancer centers in how they prevent, diagnose, and manage short-term and long-term side effects of CAR-T cell therapy.
To investigate this, the EBMT surveyed 227 European centers that provide CAR-T cell therapy. 106 centers (47%) fully answered the survey questions on topics like selecting the CAR-T product, logistics, managing cytokine release syndrome and neurotoxicity from the immune effects, as well as later phase management including low blood cell counts.
The survey found some common patterns but also significant variety between centers in how they clinically manage important aspects of CAR-T cell therapy. This shows a high need for more standardized treatment guidelines and future research in several key areas, including:
- Treating severe or steroid-resistant cytokine release syndrome/neurotoxicity
- Managing low blood cell counts
- Allowing early hospital discharge and outpatient management
- When to provide antibody replacement therapy
"Comparison of infectious complications with BCMA-directed therapies in multiple myeloma"
Source
Nath, K., Shekarkhand, T., Nemirovsky, D. et al. Comparison of infectious complications with BCMA-directed therapies in multiple myeloma. Blood Cancer J. 14, 88 (2024). https://doi.org/10.1038/s41408-024-01043-5 Accessed May 31, 2024
Overview
Researchers looked at serious infections in multiple myeloma patients treated with three different BCMA-targeted therapies - CAR-T cell therapy, bispecific antibodies (BsAb), and antibody-drug conjugates (ADC).
They studied 256 patients - 92 received CAR-T, 55 got BsAb, and 109 had ADC treatment.
The incidence (occurrence) of severe infections was highest in the BsAb group (40%) compared to the CAR-T (26%) and ADC (8%) groups. Some BsAb patients even died from infections (7%).
Comparing just the CAR-T and BsAb therapies that redirect T cells, CAR-T had a significantly lower rate of severe infections at 1 year.
During times when patients had low antibody levels, BsAb patients had more infections than CAR-T patients.
When not neutropenic, CAR-T patients had a lower severe infection risk and rate compared to BsAb.
In conclusion, BsAb therapy had a higher and more lasting risk of severe infections overall. Low antibody levels increased infection risk more with BsAb, while low white blood cell levels increased it more with CAR-T.
"Impact of Extraosseous Extramedullary Disease on Outcomes of Patients with Relapsed-Refractory Multiple Myeloma receiving Standard-of-Care Chimeric Antigen Receptor T-Cell Therapy"
Source
Dima, D., Abdallah, AO., Davis, J.A. et al. Impact of Extraosseous Extramedullary Disease on Outcomes of Patients with Relapsed-Refractory Multiple Myeloma receiving Standard-of-Care Chimeric Antigen Receptor T-Cell Therapy. Blood Cancer J. 14, 90 (2024). https://doi.org/10.1038/s41408-024-01068-w Accessed May 31, 2024
Overview
Researchers looked at serious infections in multiple myeloma patients treated with three different BCMA-targeted therapies - CAR-T cell therapy, bispecific antibodies (BsAb), and antibody-drug conjugates (ADC).
They studied 256 patients - 92 received CAR-T, 55 got BsAb, and 109 had ADC treatment.
The incidence (occurrence) of severe infections was highest in the BsAb group (40%) compared to the CAR-T (26%) and ADC (8%) groups. Some BsAb patients even died from infections (7%).
Comparing just the CAR-T and BsAb therapies that redirect T cells, CAR-T had a significantly lower rate of severe infections at 1 year.
During times when patients had low antibody levels, BsAb patients had more infections than CAR-T patients.
When not neutropenic, CAR-T patients had a lower severe infection risk and rate compared to BsAb.
In conclusion, BsAb therapy had a higher and more lasting risk of severe infections overall. Low antibody levels increased infection risk more with BsAb, while low white blood cell levels increased it more with CAR-T.