EHA 2024: Cevostamab for Relapsed and Refractory Multiple Myeloma

At the European Hematology Association (EHA) 2024 in Madrid, we had the opportunity to interview myeloma specialist Dr. Joshua Richter, Director of Myeloma Services at The Blavatnik Family – Chelsea Medical Center at Mount Sinai. He shared important insights into an emerging bispecific antibody, cevostamab, and how it can play a unique role in myeloma treatment, even when compared to other bispecific antibodies.

What Is Cevostamab? 

Cevostamab is a bispecific antibody that targets Fc receptor-homolog 5 (FcRH5) on myeloma cells and CD3 on T cells. It leads to T-cell activation and potent killing of myeloma cells.

By binding to two specific regions (FcRH5 and CD3), this therapy is more likely to destroy only myeloma cells, reducing adverse effects commonly associated with less specific agents such as infections with BCMA-targeting bispecific therapies or taste/skin issues than GPRC5D-targeting bispecific antibodies.

CAMMA-2 Trial Details

Dr. Richter highlighted data presented at EHA from the ongoing CAMMA-2 trial. This trial focuses on relapsed and refractory myeloma patients who have progressed beyond BCMA-based therapies and are looking for therapies with new targets. BCMA stands for B-cell maturation antigen. BCMA-targeting therapies for myeloma treatment that patients on this trial may have used are: 

• Bispecific antibody constructs like teclistamab (Tecvayli, Johnson&Johnson) 
• Immuno-oncology therapies, antibody-drug conjugates (ADCs) like belantamab-mafodotin (Blenrep, GSK)
• CAR T-cell therapy like idecabtagene vicleucel (ide-cel, Abecma, BMS)) and ciltacabtagene autoleucel (cilta-cel, Carvykti, Johnson & Johnson).

This clinical trial is still recruiting participants, but if successful, cevostamab could be approved as a monotherapy to treat BCMA-exposed myeloma patients.

Promising Data from the CAMMA-2 Trial 

The CAMMA-2 trial data is promising, with an overall response rate (ORR) of approximately 67%. 

Specifically, the response rate is 60% for patients who progressed after treatment with antibody conjugates (belantamab mafodotin) and 73% for those who progressed after CAR-T cell therapy.

It’s important to note that the results so far were for 21 patients, and the trial is still enrolling, so the results may change since researchers need more time to confirm them.

Side Effects of Cevostamab

The adverse effects of cevostamab included low white blood cells, anemia, and low platelets. Infections occurred in 38% of patients, and serious adverse effects occurred in 48% of patients. 

Cytokine release syndrome (CRS) occurred in 71% of patients, but all events were grade 1 or 2, meaning they weren’t more severe than the flu since the dose was increased gradually to avoid an undesired reaction. 

What are Future Implications for Myeloma Therapies?

Although the search for a myeloma cure continues, the CAMMA-2 trial has provided some of the longest durations of therapy, treatment, progression-free survival (PFS), and overall survival (OS) to date. 

Despite ongoing challenges, a 73% response rate is highly encouraging. The future approval of new drugs like cevostamab that help patients with limited options holds great promise.

The advancements in bispecific antibody treatments, particularly those targeting specific receptors in myeloma cells, represent a significant step forward in myeloma care. With continued research and clinical trials, the hope for more effective and durable treatments for myeloma patients will be the future.

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Want to Know More About Immunotherapy for Myeloma?  

• ASCO 2024: BCMA-Directed Therapies in Relapsed Multiple Myeloma
• First R/R Myeloma Patient Treated with New BCMA-Directed Bispecific Antibody in Phase 3 Study 
• What are Antibodies and How are They Used in Multiple Myeloma? 

Sources:

• A Study Evaluating the Efficacy and Safety of Cevostamab in Prior B Cell Maturation Antigen (BCMA)-Exposed Participants With Relapsed/​Refractory Multiple Myeloma (CAMMA 2)
• Initial results from the Phase I/II CAMMA 2 study show the effectiveness of cevostamab in patients with RRMM who are triple-class refractory and have received a prior BCMA-targeted ADC or CAR T-cell therapy