Norwalk, Conn., November 2, 2023 — The Multiple Myeloma Research Foundation® (MMRF®) announced today the recipients of three $7 million MMRF Myeloma Accelerator Challenge (MAC) Program Grants totaling $21 million. Each of these three-year multicenter translational projects aim to foster collaboration and advance compelling hypotheses that are ready for rapid testing in clinical trials, a critical step in the MMRF’s urgent pursuit of a cure for each and every myeloma patient.
“The MMRF makes significant strategic investments to generate robust molecular and clinical data and deliver translational research that drives better treatment options for patients,” said George Mulligan, PhD, Chief Scientific Officer at the MMRF. “These MAC Grants are a critical new part of this investment, and we are excited that the programs selected will bring together multiple centers to work in highly collaborative networks. Our strategic plan identifies specific research areas that need more attention and only through multi-center collaboration can we rapidly create a large set of patients and samples suitable for new research methods.”
The MAC Grants are focused on two critical areas of unmet need in myeloma and are part of the MMRF’s strategic priority to drive optimal treatment approaches for patients. The first is optimizing first-line therapy for high-risk newly diagnosed multiple myeloma because high-risk patients often relapse early and show inferior survival compared to standard-risk patients. The next is improving identification of high-risk smoldering multiple myeloma (HR SMM); smoldering multiple myeloma is an early, asymptomatic stage that can progress to active multiple myeloma. For each research topic, the pooling of resources and samples across a network of institutions dramatically improves the ability to drive meaningful results.
“The pace of research needs to accelerate if we are to address the significant unmet needs in multiple myeloma, and the way forward will take collaboration and funding,” said Michael Andreini, President and CEO at the MMRF. “Bringing together diverse teams through our MAC Grants that normally have many barriers to working together will bring greater focus and scale to these research priorities, yielding more timely and impactful insights for patients.”
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Sagar Lonial, MD, Winship Cancer Institute of Emory University, is leading a network of institutions including Atrium Health Levine Cancer Institute, Icahn School of Medicine at Mount Sinai, Massachusetts General Hospital, Mayo Clinic, Memorial Sloan Kettering Cancer Institute, and Dana-Farber Cancer Institute. This team will develop an improved definition of high-risk SMM through the generation and analysis of new SMM patient data. These include use of cutting-edge technologies and a large, collaborative set of patient samples, with the goal of better defining which patients are suited for early intervention, which types of interventions can have the greatest impact, and which patients can safely be observed due to a low risk of disease progression.
Prof. Pieter Sonneveld, MD, PhD, Erasmus Medical Center, is leading a European network of institutions including Erasmus Medical Center in Rotterdam, Amsterdam University Medical Centers, Julius Maximilian University of Würzburg, University of Turin, and the University of Salamanca. This team will investigate what makes less responsive, high-risk patients different from other patients with multiple myeloma. By combining different aspects of the disease, researchers will compile an integrated definition of high-risk multiple myeloma, a key step towards new treatments specifically designed for these patients.
Samir Parekh, MD, the Tisch Cancer Center at Mount Sinai, is leading a network of institutions including Albert Einstein Medical College, Hackensack University Medical Center, Stanford University Medical Center, University of California San Francisco, and Washington University of St. Louis. Using cutting-edge technologies, this team will analyze a large cohort of patient samples at the genomic and immune level to understand the critical events that drive high-risk multiple myeloma. The studies have the potential to identify new vulnerabilities that will be further studied using CRISPR gene editing in the laboratory.
Multiple myeloma is the second most common blood cancer in the US. It develops in the bone marrow and can spread throughout the body. In 2023, multiple myeloma is expected to be diagnosed in more than 35,000 Americans and take the lives of 12,000. Despite advances, most patients relapse and there is still no cure. Multiple myeloma is twice as common in the Black community compared to other ethnicities and the outcomes for Black patients are generally worse than that of white patients.
The Multiple Myeloma Research Foundation (MMRF) is the largest nonprofit in the world solely focused on accelerating a cure for each and every multiple myeloma patient. We drive the development and delivery of next-generation therapies, use data to drive optimal and more personalized treatment approaches, and empower myeloma patients with information and resources to extend their lives. Central to our mission is our commitment to advancing health equity so that all myeloma patients can benefit from the scientific and clinical advances we pursue. Since our inception, the MMRF has raised over $500 million for research, opened nearly 100 clinical trials, and helped bring 15+ FDA-approved therapies to market, which have tripled the life expectancy of myeloma patients. To learn more, visit www.themmrf.org.
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Multiple Myeloma Research Foundation Media Contact:
C.J. Volpe, Director, PR and Communications
203-652-0453
[email protected]
Is there a suggested sequence for the use of CAR T cells and bispecific antibodies?
There are two main challenges with finding the most appropriate sequence of CAR T cell therapy and bispecific antibodies. First, treatment sequencing has not been clinically addressed adequately and second, patients may not always receive the exact same sequence. Many clinicians will opt to offer CAR T cell therapy first for their relapsed/refractory patients due to the impressive response rates and duration of response. Furthermore, since CAR T cells are a “one-and-done” treatment, the time that patients get to experience off therapy allows their bodies and immune system to recover. However, CAR T-cell therapy can take several weeks to prepare which makes a patient’s disease biology an important factor to consider when deciding between a CAR T cell or a bispecific antibody. For example, patients for whom waiting a few weeks is not possible because their myeloma is aggressive (that is, fast-growing) might be better candidates for a bispecific antibody than a CAR T cell. But if the myeloma is slow-growing and there is a CAR T slot available, CAR T cell therapy would be the best choice.
However, patients shouldn’t get discouraged if they receive a bispecific antibody before CAR T cell therapy. Clinical trial data suggests that patients with relapsed/refractory multiple myeloma who are treated with CAR T therapy after bispecific antibodies can have an effective response. Furthermore, there are other types of CAR T cells under investigation that have different targets. Ultimately, bispecific antibodies are good options.
Do bispecific antibodies work in patients with high-risk multiple myeloma?
About half the patients in clinical studies of CAR T cells and bispecifics are considered high risk based on standard cytogenetic definitions like chromosomal translocation 4;14 or chromosome 17p deletion, among others. And in spite of having these cytogenetic abnormalities, patients are responding to these treatments; therefore, having high risk cytogenetics may not impact outcome as much with these types of treatments. However, most of these observations have come from single-arm studies and only a randomized, phase 3 study will help to discern whether any treatment is preferentially benefitting a high-risk subgroup of patients (for example, a large group of patients that are randomized to treatment A versus treatment B, and standard-risk and high-risk patients in each group are compared).
One type of high-risk myeloma patient that tends not to do well on bispecific antibody therapy, based on clinical study data, are those with extramedullary disease (EMD; that is, myeloma cells that are growing outside of the bone marrow). Patients with EMD do respond to treatment, but their response rate is not as high and not as long-lasting as in patients without EMD. Other strategies, such as combination therapies, are needed for these patients.
Welcome to our final day of coverage from the latest advances presented at the 20th International Myeloma Society (IMS) Annual Meeting. Highlights from today include recent findings on standard and emerging treatments including bispecific antibodies, and CAR T-cell therapy in patients with relapsed/refractory multiple myeloma (RRMM). Here’s a quick recap!
Sarclisa (isatuximab) is an anti-CD38 monoclonal antibody approved in combination with Kyprolis (carfilzomib) and dexamethasone (Isa-Kd) for patients with relapsed/refractory multiple myeloma (RRMM) after one or more prior therapy. The IKEMA trial, which compared the combination of Sarclisa, Kyprolis, dexamethasone (Isa-Kd) with Kyprolis and dexamethasone, showed that patients with RRMM (who had received 1-3 prior lines of therapy) benefit from the use of Isa-Kd, with a longer time before their disease returns (progression-free survival [PFS]) of 36 months compared to 19 months with Kd. In this final analysis of the IKEMA trial, French researchers reported a meaningful benefit in overall survival with Isa-Kd compared to Kd. Side effects associated with Isa-Kd, such as infusion reactions, diarrhea, and high blood pressure, were consistent with previous analyses, supporting it as a standard-of-care therapy for RRMM.
Yesterday we learned about the activity of venetoclax when combined with Kyprolis and dexamethasone in patients with a translocation of chromosomes 11 and 14 (t[11;14]). Today, researchers from Spain shared their findings from the Phase 3 CANOVA study that evaluated venetoclax and dexamethasone (VenDex) against pomalidomide and dexamethasone (PomDex) in patients with t(11;14)-positive RRMM who have received two or more prior treatments.
Their findings revealed that patients receiving VenDex showed a small improvement in progression free survival (the time before their disease came back) compared to PomDex (10 months vs 6 months) as well as an 8-month improvement in overall survival (32 months for VenDex compared to 24 months with PomDex. The most common side effects experienced by patients treated with VenDex included any infection, diarrhea, low white blood cell counts, and nausea (22%).
Forimtamig, a GPRC5DxCD3 T-cell-engaging bispecific antibody (BsAb), is currently being evaluated in patients with RRMM who have received one or more prior line(s) of therapy, and were refractory to a proteasome inhibitor (such as Velcade, Kyprolis or Ninlaro) and an immunomodulatory drug (such as Revlimid or Pomalyst). Forimtamig is in the same class as Talvey (talquetamab), which received FDA approval several weeks ago. Findings from an early phase study showed forimtamig induced deep and durable responses in heavily pre-treated pts and had a safety profile consistent with other investigational GPRC5D-directed therapies. (Carlo-Stella et al. ASH 2022).
In this abstract, researchers from the United Kingdom presented their analysis of clinical responses in high-risk patients. For this study, high-risk patients were defined as: age ≥65 years, >4 prior LOT, triple-class and penta-drug refractory disease, prior BCMA-targeted therapy (such as CAR-T or a bispecific antibody like Tecvayli aka teclistimab), high-risk cytogenetics (del(17p), t(4;14), t(14;16)), 1q21 gain (irrespective of other high-risk aberrations), International Staging System Stage III at baseline, and presence of soft tissue plasmacytoma (bone-based and extramedullary).
ORR across all dose levels of forimtamig was 67% and high ORRs were observed across all risk groups. Future studies will seek to identify the best dose and schedule of forimtamig for patients with RRMM.
Tecvayli (Teclistamab) was the first “off-the shelf” BCMA-targeted bispecific antibody approved for patients with heavily pretreated RRMM (patients who have received 4 or more lines of therapy). In this abstract, Dr Shonali Midha and colleagues from the Dana-Farber Cancer Institute in Boston shared their preliminary experience with the real-world use of Tecvayli. Their findings revealed that treatment with Tecvayli in a real-world setting showed similar responses to the previously reported clinical trials without any new side effects. The authors conclude that additional real-world follow up on the use Tecvayli in the real-world is needed to confirm these findings.
Carvykti (ciltacabtagene autoleucel) is approved for RRMM patients after at least four previous treatments. Given the success of CAR T-cell therapy in patients with RRMM who have failed many different treatments there is an interest in testing CAR T-cell therapy for patients who have received fewer prior therapies. Findings from the CARTITUDE-4 trial showed Carvykti significantly improved PFS compared to the standard of care (that is physician’s choice of either Pomalyst, Velcade and dexamethasone or Darzalex, Pomalyst, and dexamethasone. In this abstract, researchers from France reported findings from a prespecified subgroup of patients, including those aged < 65 yrs, patients who received 1 prior line of therapy (that is first relapse), ISS stage III, triple-class refractory, etc.
The results showed that Carvykti improved progression free survival in all subgroups, including by age, in those with high-risk features, and after first relapse. The authors conclude that these findings offer further support for the use of Carvykti in earlier lines of therapy.
Please be sure to listen to hear what myeloma experts had to say as they recap each day’s clinical research and discuss what these findings mean for myeloma patients here.
We look forward to more clinical updates in the months ahead!
Day 2 of IMS brought us some recent findings covered a mix of different drug combinations for both newly diagnosed and relapsed/refractory myeloma. Let’s dig into a big day of updates in myeloma treatment.
Revlimid is a key drug in the treatment of newly diagnosed patients with multiple myeloma. Unfortunately, due to the extensive use of Revlimid (lenalidomide)-containing regimens in the frontline setting and Revlimid-maintenance therapy, patients may develop resistance to treatment early in the disease course. Refractoriness is defined as no response to primary therapy (lenalidomide in our case) or progression within 60 days of the last dose.
Pomalyst (Pomalidomide) is approved for the use in patients who have previously received at least 2 drugs to treat multiple myeloma, including a proteasome inhibitor and Revlimid and have demonstrated disease progression on or within 60 days of completion of the last therapy. The combination of Pomalyst-Velcade (bortezomib), and dexamethasone (PVd) is a preferred option in patients who have received one ore more prior therapies, including those who have received Revlimid and Velcade.
In the first abstract, researchers from Turkey reported updates from the phase 3 OPTIMISMM, which has previously shown that PVd significantly prolonged progression-free survival (that is the length of time during and after treatment in which a patient is living with a disease that does not get worse) compared to Vd (11 vs 7 months). Participants enrolled in OPTIMISMM had a diagnosis of RRMM and had received 1-3 prior lines of therapy, including at least one round of Revlimid.
Their findings showed that patients who received PVd achieved a median overall survival (that is the length of time a patient survives) of 36 months compared with 32 months among patients treated with Vd. The most common side effects with PVd were low white blood cell counts (54%), burning/tingling in the hands and feet, also known as peripheral neuropathy (48%), and low platelet counts (40%). The researchers conclude that PVd is effective in patients for whom Revlimid is no longer a treatment option, including Revlimid-refractory patients after 1 prior line of therapy.
Venetoclax is a selective small‐molecule inhibitor of BCL‐2 that is FDA-approved for the treatment of chronic lymphocytic leukemia and has shown to be effective in treating myeloma patients with a translocation of chromosomes 11 and 14 (t[11;14]). An early phase clinical study showed that combination of venetoclax with plus Kyprolis (carfilzomib) and dexamethasone (VenKd) in RRMM showed an overall response rate (ORR) of 92% in patients who had a t(11;14).
In this abstract, Dr Jonathan Kaufman reported initial safety and efficacy data in patients with t(11;14) RRMM treated with one of 2 doses of Ven (400 or 800 mg) combined with Kyprolis and dexamethasone (Ven400Kd or Ven800Kd) compared to Kd alone. Their findings showed that patients treated with VenKd 400mg or VenKd 800mg achieved an ORR of 89% and 95%, respectively. Most common side effects observed were diarrhea, nausea, vomiting and fatigue. The incidence of side effects was higher with the higher dose of venetoclax.
This trial is ongoing and additional results will shed light on the clinical potential of venetoclax for the treatment of patients with t(11;14).
Iberdomide, Velcade, and Dexamethasone (IberVd) in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma (NDMM)
Iberdomide is a novel, potent oral cereblon E3 ligase modulator (CELMoD™) with a dual function: activate the immune system and directly kill myeloma cells by inducing the destruction of tumor-promoting proteins known as ikaros and aiolos.
In this abstract, researchers from Canada presented results from an early phase clinical trial that evaluated iberdomide in combination with Velcade and dexamethasone (IberVd). This combination has shown promising preliminary efficacy and safety in patients with RRMM in an early phase clinical trial.
Patients in the trial had untreated symptomatic NDMM, no autologous stem cell transplant planned, nor ineligibility due to age or comorbidities. Their findings showed:
The researchers concluded that IberVd showed high efficacy with deep responses in transplant ineligible patients with NDMM. The safety profile was manageable with no new safety signals, and no pts discontinued due to AEs. These findings support further assessment of iberdomide combinations in the frontline setting.
Be sure to hear what myeloma experts Dr. Sagar Lonial and Dr. Keith Stewart, had to say about the day’s presentations here.
Stay tuned for more updates from the final day at IMS 2023!
Renowned myeloma doctors and researchers from all over the world gathered in Athens, Greece at the 20th International Myeloma Society (IMS) Annual Meeting to present and discuss the latest advances in multiple myeloma research. Highlights from today included the use of risk factors to better predict minimal residual disease negativity, new findings on sustained MRD negativity with Sarclisa, Kyprolis, Revlimid, and dexamethasone in patients with high-risk myeloma, the latest results on mezigdomide, a novel cereblon E3 ligase modulator (CELMoD™) for the treatment of relapsed/refractory multiple myeloma, and the long-term benefits of using Zometa (zoledronic acid) for protection of bone disease in myeloma.
Minimal residual disease (MRD) is an important topic in the field of multiple myeloma, in large part because we have very active treatment regimens that can induce deep and sustained responses in most patients, something that was not possible just several years ago. Measuring MRD refers to counting the number of multiple myeloma cells that remain in a patient after a course of therapy is completed. Achieving MRD negativity (that is, no disease detected after treatment) in clinical trials is associated with a significantly longer time before disease progression (progression-free survival [PFS]) and overall survival; however, to date, there has been limited data on the role of sustained MRD negativity to inform whether to stop treatment. It is important to identify risk-factors of MRD resurgence and/or progressive disease (PD) among patients achieving undetectable MRD to avoid undertreatment and to test these hypotheses in clinical trials prior to adopting in clinical care.
Researchers from Spain reported their findings from an analysis of transplant-eligible MM patients enrolled in the GEM2012MENOS65/GEM2014MAIN clinical trials who achieved MRD negativity.
The only prognostic factors at diagnosis that predicted MRD resurgence and/or PD were an International Staging System (ISS) score of 3 and ≥0.01% of detectable circulating myeloma cells. Patients who achieved MRD negativity after induction (less than 6 months after starting treatment) had significantly lower risk of MRD resurgence and/or PD than those who achieved MRD negativity after 6 months from starting treatment.
The researchers conclude this model could be used in clinical trials to predict the risk of MRD resurgence and/or PD among patients achieving undetectable MRD to avoid undertreatment of transplant-eligible MM patients.
Specific cytogenetic abnormalities can be predictive of high risk of poor prognosis in patients with multiple myeloma; these include the presence of gain or amplification of chromosome arm 1q21 (gain/amp[1q21]), deletion of chromosome 1p (del[1p]), deletion of chromosome 17p (del[17p]), translocation of chromosomes 4 and 14 (t[4;14]), translocation of chromosomes 14 and 16 (t[14;16]), and translocation of chromosomes 14 and 20 (t[14;20]). MRD negativity has recently emerged as a potential surrogate for longer survival, regardless of a patient’s cytogenetic risk. Information from recent clinical trials suggests that extended intensified treatment can help achieve MRD negativity in patients who may have one or more of these high-risk features, which may lead to improved outcomes.
In the next abstract, researchers from Germany presented their findings from the phase 2 GMMG-CONCEPT trial that evaluated Sarclisa, Kyprolis, Revlimid, and dexamethasone (Isa-KRd) as induction therapy in high-risk multiple myeloma. Patients with high-risk multiple myeloma were defined by ISS stage 2 or 3 and any of del17p, t(4;14), t(14;16), or >3 copies 1q21 (amp1q21). Findings from this study were recently published in the Journal of Clinical Oncology (link). The authors showed that the combination of Isa-KRd resulted in high MRD negativity rates in patients with newly diagnosed, high-risk multiple myeloma, regardless of their transplant status.
Researchers reported:
The authors conclude that Isa-KRd effectively induces high rates of sustainable MRD negativity in the difficult-to-treat HRNDMM population, regardless of transplant status.
Mezigdomide is a novel cereblon E3 ligase modulator (CELMoD™) designed to activate the immune system and directly kill myeloma cells by inducing the destruction of tumor-promoting proteins known as ikaros and aiolos. CELMoDs are oral (taken by mouth) medications that have many similarities to immunomodulatory agents or IMiDs, but CELMoDs can be used even in patients who have relapsed after treatment with immunomodulatory agents.
In this abstract, researchers from Spain presented their findings from an early phase clinical trial that evaluated mezigdomide, a novel cereblon E3 ligase modulator (CELMoD™), in combination either Velcade and dexamethasone (MeziVd) or Kyprolis and dexamethasone (MeziVd) in relapsed/refractory multiple myeloma (RRMM) who had previously received the standard of care – a combination of three classes of drugs — and in some cases had been treated with BCMA targeting treatment, including CAR T-cell therapy. Results of the early phase trial were published online by the New England Journal of Medicine (link). Data reported from participants who received MeziVd was divided into two groups: MeziVd at varying doses (0.3, 0.6, 1.0mg) or 1.0mg of mezigdomide (MeziVd-1.0mg).
Researchers reported overall response rates (ORR) of 75% with MeziVd (either 0.3, 0.6, or 1.0mg of mezigdomide), 84% with MeziVd-1.0mg, and 85% with MeziKd.
The most frequent treatment-related side effects were low white blood cell counts (36%) and low platelet counts (21%) with MeziVd; low white blood cell counts (58%) and all infections (34%) with MeziVd-1.0mg; and low white blood cell counts (41%) and all infections (30%) with MeziKd.
With longer follow-up, MeziVd and MeziKd continued to show promising efficacy at all dose levels tested with a manageable safety profile in patients with RRMM. Future clinical trials will continue to examine the potential of this novel CELMoD in combination with other treatments.
Up to 85% of people with multiple myeloma experience bone disease. In some people, myeloma may cause thinning and weakening of the bones to the point where holes are formed in the bone, which can lead to pain or fractures. Even more patients will experience bone complications at some time point in their course of disease.
Progression of bone disease can be inhibited by treatment with Zometa. Zometa has been shown to increase quality of life and overall survival in myeloma patients, however Zometa is also associated to osteonecrosis of the jaw. The best length of treatment with Zometa is yet uncertain, as previous studies followed myeloma patients for up to 2 years.
In the final abstract, researchers from Denmark examined if treatment of myeloma bone disease up to 4 years with Zometa was safe and effective. Their findings showed that four years of monthly Zometa are superior to two years treatment in protection against progressive bone disease in multiple myeloma. The incidence of osteonecrosis of the jaw after 4 years was 4% and not significantly different between the two treatment groups. These results shed light on the clinical potential of long-term use of Zometa in protection of bone disease in myeloma.
Be sure to hear what myeloma expert, Dr. Saad Usmani, had to say about the day’s presentations here.
Stay tuned for more updates from IMS 2023!
20-year industry veteran to lead development, execution of MIF investment strategy
Norwalk, Conn., Oct. 5, 2023 — The Multiple Myeloma Research Foundation® (MMRF®) has announced the appointment of Stephanie Oestreich, Ph.D., MPA, as Managing Director of its venture philanthropy subsidiary, the Myeloma Investment Fund® (MIF®). In this role, Dr. Oestreich will lead the overall execution of the MIF’s investment strategy and serve as a member of the MMRF executive leadership team.
“We are thrilled to have Dr. Oestreich join our team as Managing Director of the MIF,” said Michael Andreini, President and CEO, the MMRF. “The MIF invests in the most promising companies that are developing innovative clinical assets and technologies that could be transformative for myeloma patients. Dr. Oestreich brings a wealth of business development experience in biopharma and biotech that will play an invaluable role in the continued growth and impact of our fund.”
Dr. Oestreich has more than 20 years of diverse experience in business development and strategic alliances spanning large biopharma, biotech, and early academic research. Previously, she served as Chief Business Officer at the biotech Galecto and Vice President at the cell therapy company Mnemo Therapeutics. In addition, Dr. Oestreich was a Venture Partner at RA Capital and Executive Vice President at Evotec, where she built its North American investment arm and started an incubator with Samsara BioCapital. Her experience also includes work at F. Roche Hoffmann-La Roche Ltd., where she served as International Business Leader, and Novartis in Business Development and in Commercial.
“The MMRF has made a tremendous impact to help advance new therapies for myeloma patients and I am truly excited to join this effort as Managing Director of the MIF,” said Dr. Oestreich. “Through the MIF’s investment strategy, we will continue our work to advance the development of novel treatments and innovative therapeutic strategies for patients.”
In addition to her role at the MIF, Dr. Oestreich currently serves on the boards of the German American Business Council in Boston and the Harvard Kennedy School’s Women’s Network and is the chair of the McCloy Alumni Association. She is also on the faculty of MIT, a member of the Launchpad Venture Group, an advisor at grIP Venture Studio to Biognosys (a Bruker company), Invitris, CART company CelineTx, and to the drug development and investment company Orange Grove Bio. She is also a member of the W20 Entrepreneurship task force, the official engagement group of the G20.
To learn more about the MIF, visit www.myelomainvestmentfund.org.
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About the Myeloma Investment Fund (MIF)
The Myeloma Investment Fund (MIF) is a venture philanthropy fund that invests in promising companies, clinical assets, and technologies in oncology to drive the development of new therapies for multiple myeloma. The MIF collaborates closely with portfolio companies to help them advance multiple myeloma research. This evergreen fund is supported entirely by philanthropy; all profits will be reinvested back into research for more effective treatments until there is a cure for every patient. For more information, visit www.myelomainvestmentfund.org.
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About the Multiple Myeloma Research Foundation (MMRF)
The Multiple Myeloma Research Foundation (MMRF) is the largest nonprofit in the world solely focused on accelerating a cure for each and every multiple myeloma patient. We drive the development and delivery of next-generation therapies, leverage data to identify optimal and more personalized treatment approaches, and empower myeloma patients and the broader community with information and resources to extend their lives. Central to our mission is our commitment to advancing health equity so that all myeloma patients can benefit from the scientific and clinical advances we pursue. Since our inception, the MMRF has committed over $500 million for research, opened nearly 100 clinical trials, and helped bring 15+ FDA-approved therapies to market, which have tripled the life expectancy of myeloma patients. To learn more, visit www.themmrf.org.
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Multiple Myeloma Research Foundation Media Contact:
C.J. Volpe, Director, PR and Communications
203-652-0453
[email protected]
Findings underscore the ongoing value to the myeloma scientific community of the MMRF’s landmark molecular and clinical data and translational research programs
Norwalk, CT, September 27, 2023 – The Multiple Myeloma Research Foundation (MMRF) today announced that findings from three studies based on analyses of its CoMMpass℠ and CureCloud℠ datasets will be featured in an oral abstract and poster presentations at the 20th International Myeloma Society (IMS) Annual Meeting in Athens, Greece, September 27-30, 2023. Topics include:
Additionally, data from the CoMMpass Study are cited in 24 posters and four education sessions, demonstrating its enduring value in driving new advancements across multiple myeloma research. With its inclusion in more than 300, CoMMpass represents the largest longitudinal genomic dataset in multiple myeloma and has led to groundbreaking discoveries that have transformed how researchers understand the biology of the disease.
To develop a more comprehensive picture of myeloma disease biology, the MMRF is expanding the CoMMpass dataset with immune data from its Immune Atlas research program. In addition, the MMRF’s CureCloud, a first-of-its-kind registry, has amassed clinical, genomic, immune, and patient-reported outcome (PRO) data across more than 1,000 participants. The MMRF makes the datasets from CoMMpass, Immune Atlas, and CureCloud available to researchers, facilitating the development of optimal treatments for all myeloma patients.
“Our consistent investment in the generation, analysis and sharing of new data with researchers worldwide accelerates the pace of scientific discovery to benefit each and every myeloma patient,” said George Mulligan, Ph.D., Chief Scientific Officer of the MMRF and co-author on two of the studies to be shared at IMS. “I am optimistic that, with greater understanding of this disease biology and continued collaboration in the research community, multiple myeloma patients will have improved therapeutic options now and also steadily increasing approaches to rational and potentially curative treatment strategies.”
About the MMRF data to be shared at IMS 2023
Friday, September 29, 2023
Poster Session 3, 1:15 PM – 2:15 PM EEST
Multi-omic analysis of multiple myeloma subtypes reveals epigenetic programs of high-risk disease
Identifying the biology of high-risk multiple myeloma is critical to improving outcomes. Current markers imperfectly predict high-risk disease and there are limited data that integrate genetic, epigenetic, and transcriptional information with outcomes. DNA methylation data was generated based on 415 samples from the MMRF CoMMpass study and identified distinct epigenetic programs of high-risk disease.
Friday, September 29, 2023
Poster Session 3, 1:15 PM – 2:15 PM EEST
Single-Cell Profiling Reveals Inflammaging-associated Dysregulations in Rapidly Progressing Multiple Myeloma Patients
Modern therapies for multiple myeloma rely on the immune system for their effectiveness and positive outcomes. Dysregulation in the immune compartment can promote disease progress and hamper the effectiveness of immune-based therapies. In this study for the characterization of bone marrow and its association with the kinetics of multiple myeloma, researchers performed Single Cell Profiling on bone marrow samples from the MMRF CoMMpass cohort.
Friday, September 29, 2023
Poster Session 3, 1:15 PM – 2:15 PM EEST
The MMRF CureCloud research study: a real-world longitudinal investigation of patient treatments and outcomes, including Patient Reported Outcome (PRO) surveys
CureCloud integrates molecular and real-world evidence data, including electronic health records (EHR) and PROs collected at six-month intervals. This poster is an analysis of the baseline PRO data. In general, patients were able to answer the PRO instruments electronically. The results indicate that younger and less socioeconomically advantaged patients experienced higher financial toxicity.
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About the Multiple Myeloma Research Foundation (MMRF)
The Multiple Myeloma Research Foundation (MMRF) is the largest nonprofit in the world solely focused on accelerating a cure for each and every multiple myeloma patient. We drive the development and delivery of next-generation therapies, leverage data to identify optimal and more personalized treatment approaches, and empower myeloma patients and the broader community with information and resources to extend their lives. Central to our mission is our commitment to advancing health equity so that all myeloma patients can benefit from the scientific and clinical advances we pursue. Since our inception, the MMRF has committed over $500 million for research, opened nearly 100 clinical trials, and helped bring 15+ FDA-approved therapies to market, which have tripled the life expectancy of myeloma patients. To learn more, visit www.themmrf.org.
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Multiple Myeloma Research Foundation Media Contact:
C.J. Volpe, Director, PR and Communications
203-652-0453
[email protected]
Norwalk, CT, August 10, 2023 – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that the U.S. Food and Drug Administration (FDA) has granted accelerated approval of Talvey™ (talquetamab-tgvs) for the treatment of patients with heavily pretreated multiple myeloma. In response to the announcement, the Multiple Myeloma Research Foundation (MMRF) has issued the following statement:
“Although options for the treatment of multiple myeloma have expanded significantly in recent years, the disease remains incurable, and therefore, patients are in need of new treatment options,” said Michael Andreini, President and Chief Executive Officer, Multiple Myeloma Research Foundation. “Today’s approval of talquetamab provides patients with a new treatment approach for relapsed or refractory disease that is a welcome addition to the myeloma community.”
According to Janssen’s announcement, Talvey™ (talquetamab-tgvs) is a first-in-class bispecific antibody for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody. To learn more about Talvey™, please visit the Standard Drug Therapies section on our website.
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About the Multiple Myeloma Research Foundation (MMRF)
The Multiple Myeloma Research Foundation (MMRF) is the largest nonprofit in the world solely focused on accelerating a cure for each and every multiple myeloma patient. We drive the development and delivery of next-generation therapies, leverage data to identify optimal and more personalized treatment approaches, and empower myeloma patients and the broader community with information and resources to extend their lives. Central to our mission is our commitment to advancing health equity so that all myeloma patients can benefit from the scientific and clinical advances we pursue. Since our inception, the MMRF has committed over $500 million for research, opened nearly 100 clinical trials, and helped bring 15+ FDA-approved therapies to market, which have tripled the life expectancy of myeloma patients. To learn more, visit www.themmrf.org.
Media Contact:
C.J. Volpe
Multiple Myeloma Research Foundation
[email protected]
203-652-0453
Several abstracts presented at this year’s American Society of Clinical Oncology (ASCO) annual meeting highlighted advances in treating newly diagnosed multiple myeloma (NDMM) and relapsed/refractory MM (RRMM). Included were several reports on bispecific antibodies (bsAbs) and combinations, as well as new data on chimeric antigen receptor (CAR) T-cell therapies—particularly its use in earlier lines of treatment for RRMM.
Researchers in Germany and Austria investigated the role of the anti-SLAMF-7 monoclonal antibody (mAb) elotuzumab in patients with NDMM in a randomized phase 3 study. Elotuzumab has demonstrated efficacy and is approved for RRMM, but its role in NDMM is unknown. Transplant-eligible NDMM patients (N=579) were randomized in a 1-to-1 ratio to receive six cycles of carfilzomib (K), lenalidomide (R) and dexamethasone (KRd) followed by four consolidation cycles of KRd and lenalidomide maintenance, all of which were given either with or without elotuzumab. Among the 574 patients who received treatment and were included in the intent-to-treat analysis, about one fourth had high-risk genetics. The coprimary outcomes of minimal residual disease (MRD) negativity and very good partial response (VGPR) or better were achieved in 49.8% of patients receiving elotuzumab plus KRd vs 35.4% of patients receiving only KRd, a significant difference (P=0.0005). Treatment-emergent adverse events (TEAEs) grade 3 or higher were slightly higher with elotuzumab (72.9% vs 62.5% in the KRd-only group). The most common adverse events (AEs) in both groups were febrile neutropenia, grade 3/4 thrombocytopenia, pneumonia, and grade 3/4 cardiac events. The researchers concluded that the addition of elotuzumab significantly improved the rate of early, deep MRD-negative remission in the frontline setting.
Investigators at Emory University found that carfilzomib, pomalidomide, dexamethasone (KPd) deepened responses in patients with high-risk NDMM (ie, presence of t[4;14], t[14;16], del17p, circulating plasma cells, or double-hit myeloma) who had achieved a partial response or better after initial treatment with autologous stem cell transplant. Patients (N=29) were treated with KPd; at study entry, 24.1% of patients had achieved a complete response (CR) or better, and 68.9% had a VGPR or better. By the end of the study, these values reached 79.3% and 100%, respectively. Of the 15 patients evaluable for MRD, MRD (10-5) and (10-6) was achieved in 80% and 53.3%, respectively. After a median follow-up of more than 2 years, the 36-month PFS was 63.2% and 36-month overall survival (OS) was 72.4%. Of the six patients who died while on the study, five died from progressive disease. TEAEs occurring in 20% or more of patients were fever (37.9%), fatigue (34.5%), grade 3/4 diarrhea (27.6%), nausea (24.1%), cough (20.7%), muscle cramps (20.1%), and acneiform rash (20.1%). About 10% of patients experienced grade 3/4 cardiac AEs, and 17.2% experienced grade 3/4 cataracts. Although responses were deepened in this high-risk population, progression-free survival (PFS) and OS remained poor, indicating that strategies for sustaining remission warrant further study.
In the RRMM setting, several studies evaluated the role of bsAbs both alone and in combination with other therapies.
In October 2022, the FDA approved teclistamab, the first bsAb (BCMA×CD3), for patients with RRMM who have received at least four prior lines of therapy including the three main classes of myeloma therapy (proteasome inhibitor [PI], immunomodulatory drug [IMiD], and anti-CD38 mAb) based on the results of the MajesTEC-1 study. Previously published results after 14 months of follow-up showed that teclistamab achieved an overall response rate (ORR) of 63%, with 39% of patients achieving a CR or better, as well as a median duration of response (DOR) of 18.4 months and a median PFS of 11.3 months.
Presented at this year’s ASCO was extended follow-up data (median follow-up: 22 months) from MajesTEC-1. Of 165 patients receiving teclistamab at the recommended phase 2 dose (RP2D; 1.5 mg/kg every week), 43% achieved a CR or better; median DOR was 24 months, with a median PFS of 12.5 months, and a median OS of 21.9 months. Hematologic AEs (any grade) included neutropenia (72%), anemia (54%), thrombocytopenia (42%), and lymphopenia (35%). Infections occurred in 78% of patients (52% grade 3/4), and nine immune effector cell-associated neurotoxicity syndrome (ICANS) events (all grade 1/2) were reported in five patients. Of the 49 patients continuing on the study, about 90% continue to receive dosing every 2 weeks. The authors suggest that the responses are deep, durable, and independent of refractory status, supporting teclistamab as a “safe and effective off-the-shelf BCMA bispecific therapy for patients with RRMM.”
Results from the phase 1/2 LINKER-MM1A study of the bsAb linvoseltamab (BCMA×CD3) in patients with RRMM were also reported at ASCO. Patients had progressed on at least three lines of therapy, including a PI, IMiD, and an anti-CD38 antibody, or were at least triple class (IMiD/PI/anti-CD38 Ab) refractory. Data published in advance of the meeting suggested that higher efficacy was observed with the 200-mg compared with the 50-mg dose, including in patients with high disease burden. The ORR for the 200-mg group (n=58) was 64% vs 50% with the 50 mg cohort (n=104). Median DOR was not reached for either cohort after median follow-up of 2.3 months for the 200-mg dose group and 4.7 months for the 50-mg dose group. A response at 6 months was seen in 89% of patients in the 200-mg group and 85% in the 50-mg group. The most common TEAEs were CRS, fatigue, and anemia. Grade ≥3 ICANS occurred in two patients in the 200-mg cohort and one patient in the 50-mg cohort. About 8% of patients in both groups discontinued treatment due to AEs. Infections occurred in 43% (Grade 3/4: 26%) in the 200-mg cohort and 59% (Grade 3/4: 31%) in the 50-mg cohort.
Another investigational bsAb, elranatamab (BCMA×CD3), is under FDA Priority Review for the treatment of patients with RRMM. A pooled analysis of 86 patients with RRMM previously treated with BCMA-directed approaches from the MagnetisMM clinical trials program found that elranatamab is safe and effective in this population. Previous BCMA-directed treatment included an antibody-drug conjugate (ADC; 67.4%), CAR T cells (41.9%), or both (9.3%). After a median follow-up of 10.3 months, ORR was 45.3% (41.4% with prior ADC and 52.8% with prior CAR T) and CR or better was achieved in 17.4% of patients. Median PFS was 4.8 months, and median OS was not reached by 10 months, with an OS rate of 60.1% at 9 months. Most common TEAEs were cytokine release syndrome (CRS; 65.1%), anemia (59.3%), neutropenia (44.2%), and thrombocytopenia (40.7%). ICANS was reported in 5.8% of patients. According to the researchers, these results support the use of elranatamab in RRMM and who have had prior exposure to BCMA-directed therapies.
A combination of two novel bsAbs, teclistamab and talquetamab, has shown promise with respect to both response rate and safety profile in RRMM. Teclistamab is the first BCMA-directed bsAb approved for the treatment of triple-class–exposed RRMM, and talquetamab is an experimental bsAb targeting the myeloma antigen G protein–coupled receptor 5D (GPRC5D×CD3). The multinational team of researchers behind the phase 1b RedirecTT-1 trial combining teclistamab and talquetamab proposed that targeting both antigens simultaneously might help overcome resistance mechanisms, such as antigen escape. The trial included 63 patients with RRMM and sought to identify the recommended phase 2 regimen (RP2R) for the combination. This was a heavily pretreated group, with patients having received a median 5 (1–11) prior treatments. Common TEAEs included CRS (81%), neutropenia (76%), and anemia (60%). One case of ICANS was reported. The ORR at the RP2R was 92% (12/13) among all evaluable patients. Of the 43% of patients who had extramedullary disease (EMD), the ORR was 83%. The researchers determined that, based on the results, this combination warrants further study in patients with high-risk EMD, for whom treatment options are currently limited.
Another study involving talquetamab (GPRC5D×CD3) evaluated this bsAb in combination with the anti-CD38 mAb daratumumab in patients previously treated with at least three lines of therapy. Preliminary results from the TRIMM-2 study showed promising efficacy for this combination, with the potential for a synergistic effect between the two agents. Updated results from 65 patients over a median follow-up of 11.5 months showed an ORR in about three fourths of the patients, with responses deepening over time. ORRs in patients exposed/refractory to prior therapy were 75%/76% for anti-CD38, 74%/64% for anti-BCMA, and 75%/75% for bsAb. At 12 months, 86% of responders, and 89% of patients with a CR or better, continued to show responses. Common AEs included CRS (78%; all grade 1/2), dysgeusia (75%), dry mouth (55%), anemia (52%), fatigue (45%), and skin exfoliation (45%). At data cutoff, 84% of responders remained on therapy, and the median PFS was 19.4 months, with 12-month PFS and OS rates of 76% and 93%, respectively. According to the researchers, the results from this steroid-sparing combination showed manageable safety and promising results in this heavily pretreated patient population, including patients refractory to anti-CD38/BCMA and T-cell redirecting therapies.
Risk of Infection With Bispecific Antibodies
Targeting BCMA and GPRC5D in RRMM with bsAbs has been associated with an increased infection risk, but this association requires further clarification. To investigate this issue, researchers followed 80 patients treated with 86 courses of bsAb therapy in early-phase clinical trials conducted between 2019 and 2022. Of the patients, 56 received BCMA bsAb,15 received GPRC5D bsAb combined with CD38 mAb with or without IMiDs, and 15 received GPRC5D bsAb monotherapy. A total of 117 infections were reported, 89 in the BCMA group, 24 in the GPRC5D combination group, and 4 in the GPRC5D monotherapy group. The infection rates were similar among patients receiving BCMA bsAb and GPRC5D bsAb, but the incidence of high-grade infections (grade ≥3) was higher with BCMA bsAb treatment (P=0.01). Grade 5 events were observed in 8% (n=7) of patients treated with BCMA bsAb compared to none treated with GPRC5D bsAb. According to the researchers, the findings suggest that the risk of infection with bsAb therapy is high in RRMM, and the risk is higher for BCMA bsAb compared to GPRC5D bsAb, with higher cumulative incidence of infection, higher-grade infection, and more infections that require hospitalization.
Another study investigated infections associated with talquetamab. In the phase 1/2 MonumenTAL-1 study, a total of 339 patients with RRMM received subcutaneous talquetamab, either once a week (n=143) or every 2 weeks (n=145); in addition, 51 had prior T-cell redirection therapy. The researchers found that new-onset infections were most likely to occur during the first two cycles of treatment. Grade 3/4 infections observed in more than two patients included pneumonia (3.5%) and urinary tract infection (2.1%) with the once weekly dose; and pneumonia (2.1%) and COVID-19 (2.1%) with the every-2-weeks dose. Among patients receiving prior T-cell redirection therapy, 6% developed pneumonia. According to the researchers, the rate of opportunistic infections was low with talquetamab, as were rates of discontinuation and deaths. Although not directly compared in this study, infection rates, particularly rates of fatal infections, appear lower with talquetamab than with BCMA-targeted T-cell–based therapies, the authors concluded.
Based on results from the CARTITUDE-1 trial, the FDA in February 2022 approved ciltacabtagene autoleucel (cilta-cel) for the treatment of adult patients with RRMM who had received at least four lines of therapy, including a PI, an IMiD, and an anti-CD38 mAb. Final results from CARTITUDE-1 were presented at this year’s ASCO. A total of 97 patients received cilta-cel over a median follow-up of 33.4 months (range, 1.5–45.2). Median DOR was 33.9 months; median PFS was 34.9 months, with an estimated 47.5% of patients maintaining response at 36 months. According to the researchers, the typical median OS in the heavily pretreated RRMM setting is only about 12 months, highlighting a substantial improvement with cilta-cel in this trial. Out of 49 patients evaluable for MRD, 26 remained MRD-negative for 12 months or more. Of those patients, 20 sustained an MRD-negative CR or better. In addition, 18 patients were MRD negative with a CR or better 24 months after infusion. Safety of cilta-cel was as expected. Overall, six new cases of second primary malignancy were reported, including two cases of basal cell carcinoma and one case each of myelodysplastic syndrome, B-cell lymphoma, melanoma, and prostate cancer. According to the researchers, the median PFS with a single infusion of cilta-cel is longer than that observed with any previously reported therapy in this setting. The ongoing CARTINUE study will follow the course of these patients over a 15-year period.
A retrospective study of data also indicated favorable outcomes for cilta-cel as standard-of-care (SOC) therapy in patients with RRMM. Overall, 177 patients from 12 US academic medical centers were leukapheresed and 139 received cilta-cel. Many patients (55%) in this analysis would have been considered ineligible to enroll in CARTITUDE-1. Of the patients, 83% received bridging chemotherapy, with an ORR of 28%. CRS (grade ≥3: 7%) developed in 81% and ICANS (grade ≥3: 8%) developed in 22% of patients. Infections were seen in 32% of patients. Best response rates, recorded in 118 patients, were partial response (PR) or better (80%); VGPR or better (62%); and CR or better (40%). The authors concluded that intended SOC with cilta-cel has a favorable ORR despite the fact that a larger proportion of patients in this analysis had high-risk features relative to CARTITUDE-1 trial patients; for example, more patients in the current study had EMD (35%) compared with the CARTITUDE-1 study (~14%).
A late-breaking abstract presenting data from the CARTITUDE-4 phase 3 trial reported that compared with SOC (pomalidomide, bortezomib, and dexamethasone [PVd] or daratumumab, pomalidomide, and dexamethasone [DPd]), a single infusion of the dual-binding BCMA-targeting CAR T-cell therapy cilta-cel was associated with a significant improvement in PFS in patients with lenalidomide-refractory MM after first relapse. CARTITUDE-4 represents the first phase 3 study designed to evaluate the efficacy and safety of CAR T-cell therapy in patients with lenalidomide-refractory MM after first relapse, including patients earlier in the course of disease and treatment than were included in previous CARTITUDE trials.
CARTITUDE-4 included 419 patients with lenalidomide-refractory MM who had received between one and three lines of therapy, including a PI and IMiD. In the cilta-cel arm (n=208), patients received bridging therapy with physician’s choice of either PVd or DPd followed by a single cilta-cel infusion 5 to 7 days after lymphodepletion. No manufacturing failures were reported. In the SOC arm, patients received either PVd (n=28) or DPd (n=183) until disease progression. During a median follow-up period of 16 months, the 12-month PFS rates were 76% versus 49% for cilta-cel and SOC, respectively (HR 0.26; P<0.0001). Cilta-cel was associated with a significantly improved ORR (P<0.0001) and an improved number of CR or greater responses (P<0.0001) compared with SOC. MRD negativity rate was also improved with cilta-cel (P<0.0001). In addition, there was a positive trend toward improved OS in the cilta-cel arm (HR=0.78). Grade 3/4 AEs occurred in 97% and 94% of patients treated in the cilta-cel or SOC arms, respectively (including infections [27% vs 25%] and cytopenias [94% vs 86%]). In the cilta-cel arm, 76% had CRS (1% grade 3; no grade 4/5), 5% had ICANS (all grade 1/2) and one patient had a grade 1 movement/neurocognitive AE.
Researchers from the Dana-Farber Cancer Institute and others presented results from a phase 1 study of PHE885, a T-charge–manufactured BCMA-directed CAR T-cell therapy in patients with RRMM. BCMA-directed CAR T-cell therapies have been approved for RRMM, though implementation in clinical practice is subject to lengthy manufacturing times and strong demand for access. According to the researchers, T-charge manufacturing can shorten manufacturing time to less than 2 days and preserve T cell stemness, resulting in rapid expansion and prolonged CAR T-cell persistence.
In the current study, PHE885 produced high response rates with no unexpected safety findings in heavily pretreated patients with RRMM. A total of 46 patients were evaluated with a range of doses of PHE885. Patients had a median of 4 (2–10) prior lines of treatment, 37% had EMD, and 96% were triple-class refractory. Although these patients had aggressive disease, only 28% required bridging therapy due to the quick production time of PHE885. CRS of any grade was noted in 96% of patients and ICANS occurred in 22% (7% grade 3). Other common treatment-related grade 3/4 AEs included anemia (54%), neutropenia (50%), and thrombocytopenia (37%). In the 43% of patients evaluable for efficacy, ORR was 98%. Of 10 evaluable patients, 6 were MRD negative at 10-5 (by next-generation sequencing).
Data from a phase 1 study of another rapid CAR T-cell therapy, GC012F, was presented by several research groups based in China. GC012F is a BCMA/CD19 dual-targeting fast CAR T-cell therapy. According to the researchers, the novel FasT CAR-T platform enables manufacturing of the treatment in 22 to 36 hours. In data previously reported by the group, GC012F led to deep and durable responses in 29 patients with RRMM. The latest data presented at ASCO included 12 months of efficacy follow-up for these patients, 90% of whom had high-risk disease (by Stratification for Myeloma and Risk-Adapted Therapy [mSMART]). ORR was 93.1% (27/29), stringent CR was 82.8% (24/29), and 89.7% achieved a VGPR or better. GC012F was still detectable in 23 patients at 6 months and in 16 patients at 12 months after infusion, with a median time of persistence of 410 days. All 29 patients achieved MRD negativity by flow cytometry (sensitivity 10-4 to 10-6). The median DOR was 37.0 months, and the median PFS was 38.0 months. Of the 29 patients, 25 had CRS of any grade, but no cases of ICANS were observed. The researchers noted that these updated results show that GC012F provides deep and durable responses along with a very high MRD negativity rate, suggesting that GC012F warrants further investigation in this setting.
Belantamab mafodotin (belamaf) is an antibody-drug conjugate that targets BCMA. In November 2022, the manufacturer of belamaf (GSK) initiated the process for withdrawing belamaf from the US market based on findings from DREAMM-3, which did not meet the requirements of the FDA Accelerated Approval regulations. Patients included in DREAMM-3 had RRMM at second relapse and were receiving third-line or later treatment. New results from the DREAMM-3 phase 3 trial in RRMM suggest that belamaf produced more durable and deeper responses compared to the comparator of pomalidomide plus low-dose dexamethasone (Pd); however, no difference was observed in PFS between the two groups. A total of 325 patients were randomized in a 2:1 ratio to receive belamaf or Pd. Over a median duration of follow-up of 11.5 months, median PFS was longer with belamaf (11.2 months vs 7.0 months), but the PFS was similar between the treatment groups (P=0.558). Belamaf appeared to induce deeper responses compared with Pd and showed a longer DOR: at 12 months, the probability of maintaining response was 0.768 with belamaf vs 0.484 with Pd. The safety profile was consistent with previous reports for belamaf and Pd. Current research efforts with respect to belamaf are focusing on its role in combination with established and novel agents.
Another study of belamaf, DREAMM-9, evaluated this agent in combination with bortezomib, lenalidomide, and dexamethasone (VRd) in a phase 1 study in patients with transplant-ineligible NDMM. Data from the updated interim analysis suggested that belamaf plus VRd had no new safety signals and provided early and deep antimyeloma responses in this setting. Patients were separated into seven different cohorts including 12 to 14 patients each. Grade ≥3 AEs occurred in 35% of patients and led to belamaf dose reductions in 7% and dose delays in 63% of all treated patients. The most commonly reported nonocular AEs across all cohorts were thrombocytopenia (46%), constipation (36%), diarrhea (34%), and peripheral sensory neuropathy (31%). Of the patients, 100% of patients in two cohorts, both at the highest dose of 1.9 mg/kg responded. Median time to VGPR or better ranged from 2.1 to 3.1 months (months) across cohorts.
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Jointly provided by the MMRF and RedMedEd.
This educational activity is supported by educational grants from Bristol Myers Squibb and GSK.
