Dr Mohty on the Potential Role of BCMA-Targeted Bispecific Antibodies in Myeloma

Mohamad Mohty, MD, PhD, professor, hematology, Sorbonne University, head, Clinical Hematology and Cellular Therapy Department, Saint-Antoine Hospital discusses the potential role of treatment with BCMA-targeted bispecific antibodies in the treatment of multiple myeloma.

There have been significant strides made in the treatment armamentarium for patients with relapsed/refractory multiple myeloma, Mohty begins, specifically for those patients who may be triple-exposed or triple-refractory.

Currently, Mohty notes that BCMA-targeted bispecific antibodies are primarily utilized in the treatment of patients with advanced relapsed or refractory disease. These targeted approaches have shown efficacy in this setting, offering a new therapeutic option for patients who have exhausted other treatments. Future research aveneus will focus on moving these bispecific antibodies into earlier lines of therapy, aiming to further enhance patient outcomes in the long run, Mohty explains.

Besides integrating BCMA targeted therapies into earlier lines of treatment, Mohty mentions another area of exploration which will assess the combination of bispecific antibodies with other therapeutic modalities.

Mohty says that possible approaches may include pairing bispecific antibodies with immunomodulatory drugs, anti-CD38 monoclonal antibodies, or even with other bispecific antibodies targeting different antigens. These combinations are anticipated to enhance therapeutic efficacy by leveraging multiple mechanisms of action, potentially leading to deeper and more durable responses in patients with multiple myeloma. The development of these novel combinations is expected to be a key focus of research over the next 5-10 years, Mohty emphasizes.

The future use of BCMA-targeted bispecific antibodies in multiple myeloma appears promising, particularly as these agents are integrated into earlier treatment lines and combined with other therapies, he notes. Ongoing research is necessary to determine the most effective strategies for incorporating these innovative treatments into clinical practice, with the goal of achieving better outcomes for patients with myeloma, Mohty concludes.

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Mohamad Mohty, MD, PhD, discusses the potential role of BCMA-targeted bispecific antibodies in myeloma.

Dr Mohty on the Implications of Real-World Efficacy With Elranatamab in R/R Myeloma

Mohamad Mohty, MD, PhD, professor, hematology, Sorbonne University, head, Clinical Hematology and Cellular Therapy Department, Saint-Antoine Hospital, shares the rationale for investigating the real-world efficacy of elranatamab-bcmm (Elrexfio) in patients with relapsed/refractory multiple myeloma.

Mohty begins by stating there have been significant advancements in the treatment of patients with relapsed/refractory multiple myeloma, especially for those who are triple-exposed or triple-refractory. These patients have been treated with an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an IMiD, which makes their disease particularly challenging to manage when it relapses, he explains. Immunotherapies have emerged as a beacon of hope for this patient group, offering potential new avenues for treatment, according to Mohty. These therapies can be administered as either cellular therapies, such as CAR T cells, or bispecific antibodies, Mohty says. Selecting the right target for these therapies is essential, and BCMA has proven to be a highly effective target, he adds.

As a result, BCMA-directed therapies have been approved by regulatory agencies and are in clinical use, Mohty reports, adding that bispecific antibodies targeting BCMA have also been approved. The approvals of these agents were based on the outcomes of single-arm clinical trials, which demonstrated their efficacy, feasibility, and safety profiles, he explains.

Although clinical trials provide crucial data for approval, it is equally important to gather information on the use of these therapies outside of the trial setting, Mohty elucidates. Real-world patients tend to have some of the most difficult multiple myeloma cases to treat, and studies evaluating these patients provide valuable insights into the real-world application of these therapies, he notes.

The study investigating the real-world efficacy of elranatamab in patients with relapsed/refractory multiple myeloma used data from the French compassionate use program, Mohty expands. The findings highlighted the importance of real-world data in understanding the effectiveness and safety of new treatments for patients with relapsed/refractory multiple myeloma, particularly those who have exhausted conventional treatment options, he says. By examining these real-world applications, oncologists can better assess the impact of innovative therapies and refine treatment strategies to improve patient outcomes, Mohty concludes.

Mohamad Mohty, MD, PhD, shares the rationale for investigating the real-world efficacy of elranatamab in relapsed/refractory multiple myeloma.

Dr Mohty on the Real-World Efficacy of Elranatamab in R/R Multiple Myeloma

Mohamad Mohty, MD, PhD, professor, hematology, Sorbonne University, head, Clinical Hematology and Cellular Therapy Department, Saint-Antoine Hospital, discusses findings from the French compassionate use program evaluating the real-world efficacy of elranatamab-bcmm (Elrexfio) in patients with relapsed/refractory multiple myeloma.

This retrospective analysis assessed the efficacy and safety of elranatamab in 101 patients from 22 centers who received the agent between 2022 and 2023. Most of the patients observed in this study would have been considered ineligible for enrollment in the registrational, phase 2 MagnetisMM-3 trial (NCT04649359). Findings from this study supported the 2023 

 for the treatment of patients with relapsed/refractory multiple myeloma who have received 4 or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Although the patient population observed in this study had unfavorable characteristics and disease features, at a median follow-up of 15.5 months (range, 3.4-18.8), the overall response rate (ORR) with elranatamab was 51.5%. This aligns with response rates that have been previously reported with the agent in more favorable patient populations, Mohty says. Importantly, 42% of these responses were very good partial responses (VGPRs) or better, which is encouraging to see since the quality of responses often correlates with improved outcomes, Mohty emphasizes. Furthermore, 22% of patients had a VGPR or better after 1 cycle of treatment.

Progression-free survival data from the study are difficult to assess, Mohty notes. He explains that this was not a clinical trial, so prespecified time to progression was not included. However, investigators were able to accurately assess duration of response (DOR), according to Mohty. The median DOR was 11 months (95% CI, 8-not assessed), and 48% of patients (95% CI, 31.1%-64%) had responses lasting at least 1 year. The 1-year overall survival rate was 42% (95% CI, 31.7%-52.1%). Overall, these study findings established the efficacy of elranatamab in this difficult-to-treat patient population, Mohty concludes.

Mohamad Mohty, MD, PhD, discusses the real-world efficacy of elranatamab in patients with relapsed/refractory multiple myeloma.

Mohamad Mohty, MD, PhD, professor, hematology, head, the Hematology and Cellular Therapy Department, Saint-Antoine Hospital and Sorbonne University, discusses the promise of the phase 2 MagnetisMM-3 trial (NCT04649359) in patients with relapsed/refractory multiple myeloma, which is investigating elranatamab (PF-06863135) monotherapy in this patient population.

In this open-label, international trial that is evaluating the efficacy of the novel bispecific antibody elranatamab, patients received 76 mg of subcutaneous elranatamab once weekly in 28-day cycles. At the 2023 EHA Congress, investigators found that at a median follow-up of 14.7 months (range, 0.2-25.1), the overall response rate was 61.0% (95% CI, 51.8%-69.6%), 35.0% of patients achieved a complete response (CR) or stringent CR, and 56.1% of patients achieved a very good partial response or better. Among evaluable patients, the median time to response was 1.2 months (range, 0.9-7.4).

Based on these beneficial outcomes, it is believed that it is possible for patients to achieve excellent progression-free survival outcomes with elranatamab while also a maintaining a good safety profile, Mohty begins. For example, the step-up dosing regimen and mode of administration of elranatamab allowed the trial investigators to limit the incidence of severe cytokine release syndrome and neurotoxicity, he emphasizes.

Regarding infections, important information was derived from patients who switched dosing after 6 cycles to receive the agent every 15 days, Mohty continues. Notably, the investigators saw a clear trend toward a decrease in infectious complications with this change to the dosing schedule. This is important, as it suggests that patients may be able to receive treatment less frequently, Mohty says.

The majority of patients who switched treatment schedules were able to maintain their responses over time, and the 15-month follow-up data show a positive risk balance, Mohty continues. These data provide an excellent foundation for the continued development of this bispecific antibody, Mohty concludes.

Mohamad Mohty, MD, PhD, discusses the promise of the phase 2 MagnetisMM-3 trial in patients with relapsed/refractory multiple myeloma, which is investigating elranatamab monotherapy in this patient population.

Dr Mohty on the Promise of Elranatamab in Relapsed/Refractory Multiple Myeloma

Mohamad Mohty, MD, PhD, professor, hematology, head, the Hematology and Cellular Therapy Department, Saint-Antoine Hospital and Sorbonne University, discusses unmet needs in patients with relapsed/refractory multiple myeloma and the rationale for investigating elranatamab (PF-06863135) monotherapy in this population in the phase 2 MagnetisMM-3 trial (NCT04649359).

MagnetisMM-3 is an open-label, international trial evaluating the efficacy of elranatamab, a novel bispecific antibody, in patients with relapsed/refractory multiple myeloma. Elranatamab targets both BCMA-expressing myeloma cells and CD3-expressing T cells. As a class of drugs, bispecific antibodies use immune therapy to target cancers, such as malignant plasma cells in multiple myeloma, Mohty says.

Cohort A of MagnetisMM-3 enrolled 123 patients with relapsed/refractory disease who had received no prior BCMA-directed therapies. These patients had a median of 5 prior lines of therapy (range, 2-22), and all patients were triple-class refractory, meaning they had each received and progressed on at least 1 prior immunomodulatory drug, proteasome inhibitor, and anti-CD38 monoclonal antibody. This population has historically had limited treatment options, and bispecific antibodies represent new potential options, Mohty emphasizes.

In MagnetisMM-3, patients received 76 mg of subcutaneous elranatamab once weekly in 28-day cycles. Overall response rate (ORR) by blinded independent central review (BICR) served as the primary end point of this trial, with key secondary end points including duration of response, complete response (CR) rate, time to response, progression-free survival, minimal residual disease (MRD)–negativity rate, overall survival, and safety.

At a median follow-up of 14.7 months (range, 0.2-25.1), the confirmed ORR by BICR was 61.0% (95% CI, 51.8%-69.6%), including a CR/stringent CR (sCR) rate of 35.0% and a very good partial response rate of 56.1%. Among evaluable patients who achieved a CR/sCR, 89.7% achieved MRD negativity at the sensitivity threshold of 10–5. Of the patients who responded, the median time to response was 1.2 months (range, 0.9-7.4).

Mohamad Mohty, MD, PhD, discusses unmet needs in patients with relapsed/refractory multiple myeloma and the rationale for investigating elranatamab monotherapy in this population in the phase 2 MagnetisMM-3 trial. 

Dr Mohty on Bispecific Antibodies in R/R Multiple Myeloma

Mohamad Mohty, MD, PhD, professor of Hematology and head of the Hematology and Cellular Therapy Department at Saint-Antoine Hospital and Sorbonne University in Paris, France, discusses extended follow-up from cohort A of the phase 2 MagnetisMM-3 trial (NCT04649359) of elranatamab (PF-06863135) monotherapy in patients with relapsed/refractory multiple myeloma who received at least 1 proteasome inhibitor, 1 immunomodulatory drug, and 1 anti-CD38 antibody, and were naïve to BCMA-directed therapies.

Data presented at the 2023 EHA Congress showed that among all evaluable patients in cohort A (n = 123), elranatamab elicited an overall response rate (ORR) of 61.0% (95% CI, 51.8%-69.6%), including a stringent complete response (sCR) rate of 15.4%, a complete response (CR) rate of 19.5%, a very good partial response rate (VGPR) of 21.1%, and a partial response (PR) rate of 4.9%. In patients who received 2 or 3 prior lines of therapy (n = 26), the ORR was 73.1% with sCR, CR, VGPR, and PR rates of 19.2%, 26.9%, 23.1%, and 3.8%, respectively.

Additional data showed that the ORR and CR or better rate for patients without extramedullary disease (n = 84) were 71.4% and 40.5%, respectively. Those rates were 75.0% and 53.6%, respectively, for those with Revised International Staging System stage I disease (n = 28). 

The median time to response for the overall population was 1.2 months (range, 0.9-7.4). Among evaluable patients who achieved a sCR or CR (n = 29), the minimal residual disease–negativity rate at a 10

At a median follow-up of 14.7 months for the overall population in cohort A, the median progression-free survival (PFS) and overall survival (OS) had not yet been reached. The 15-month PFS and OS rates were 50.9% and 56.7%, respectively. The 15-month duration of response rate was 71.5%. The survival rates observed thus far are promising, if not unprecedented, for this patient population, Mohty concludes.

Mohamad Mohty, MD, PhD, discusses extended follow-up from cohort A of the phase 2 MagnetisMM-3 trial of elranatamab in patients with relapsed/refractory multiple myeloma.

Mohamad Mohty, MD, PhD

Articles

Dr Mohty on the Potential Role of BCMA-Targeted Bispecific Antibodies in Myeloma

Dr Mohty on the Implications of Real-World Efficacy With Elranatamab in R/R Myeloma

Dr Mohty on the Real-World Efficacy of Elranatamab in R/R Multiple Myeloma

Dr Mohty on the Promise of Elranatamab in Relapsed/Refractory Multiple Myeloma

Dr Mohty on Bispecific Antibodies in R/R Multiple Myeloma

Dr Mohty on Extended Follow-up Data from MagnetisMM-3 With Elranatamab in R/R Myeloma