Elranatamab for RRMM: Updates from the MagnetisMM trials

On August 14, 2023, the U.S. Food and Drug Administration (FDA) granted accelerated approval to elranatamab for the treatment of relapsed/refractory multiple myeloma (RRMM) in patients who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody. This approval was based on data from the MagnetisMM-3 clinical trial which is summarized here alongside the alternative MagnetisMM trials.⁴

Elranatamab is an investigational B-cell maturation antigen (BCMA) CD3 bispecific antibody currently under investigation in relapsed/refractory multiple myeloma (RRMM) as part of the MagnetisMM trials.¹ The latest results from the MagnetisMM trials were presented at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition,¹ the European Hematology Association (EHA) 2023 Hybrid Congress,² and the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.³

Here, we summarize key safety and efficacy data from the presentations of elranatamab in RRMM and in BCMA-naïve and -exposed subgroups.

MagnetisMM

The interventions and designs of the MagnetisMM trials included in this review are outlined in Table 1.

Table 1. Study design overview*

Elranatamab in RRMM (MM-1)¹

The latest data from MagnestisMM-1 includes 55 patients with RRMM, dosed at 250–1,000 µg/kg either weekly or fortnightly with subcutaneous elranatamab.

At a median follow-up of 12 months, 64% of patients achieved an overall response (ORR), with 10% achieving a complete response (CR), 7.3% a partial response, and 18.2% a very good partial response.

Secondary endpoint data:

• Median duration of response in responders (n = 35): 17.1 months
• Median progression-free survival: 11.8 months
• Measurable residual disease (MRD) negativity at any point: 100%
• MRD negativity at >6 months: 62%

Elranatamab in BCMA-naïve RRMM (MM-3)²

These data include the updated response and safety data at a 15-month follow up of the 123 patients who were BCMA-naïve from the MagnetisMM-3 trial. In the total cohort, an ORR of 61% was recorded, with 34.9% at CR or stringent CR. This cohort was divided into subgroups including by number of previous therapies and presence of extramedullary disease. Responses in these patient subgroups are shown in Figure 1.

Figure 1. Response rates in BCMA-naïve patients* 

BCMA, B-cell maturation antigen; CR, complete response; EMD, extramedullary disease; LOT, line of therapy; ORR, overall response rate; PR, partial response; R-ISS, revised International Staging System; sCR, stringent complete response; VGPR, very good partial response.
*Data from Mohty.²

Secondary endpoint data:

• MRD negativity at any point in patients who achieved CR/stringent CR (n = 29): 89.7%
• Median time to response in responders (n = 75): 1.2 months

Elranatamab in BCMA-exposed RRMM (MM-1, -2, -3, and -9)³

In a pooled analysis from the MagnetisMM-1, -2, -3, and -9 trials of patients who were exposed to ≥1 proteasome inhibitor, immunomodulatory drug, anti-CD38 antibody, and BCMA-directed therapy; 87 patients were evaluated for their response to elranatamab based on previous BCMA exposure. In the total population of exposed patients, an ORR of 46% was recorded, with a higher ORR of 52.8% in patients previously treated with CAR T-cell therapy (Figure 2).

Figure 2. Response rates in BCMA-exposed patients* 

ADC, antibody–drug conjugate; BCMA, B-cell maturation antigen; CAR-T, chimeric antigen receptor T cell therapy; CR, complete response; ORR, overall response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.
*Data from Nooka.³

Median progression-free survival, overall survival (OS), and duration of response data are presented in Figure 3, with the prior antibody-drug conjugate and prior CAR T-cell therapy groups provided for comparison.

Figure 3. Secondary endpoint data in BCMA-exposed patients* 

ADC, antibody–drug conjugate; BCMA, B-cell maturation antigen; CAR-T, chimeric antigen receptor T-cell therapy; OS, overall survival; PFS, progression-free survival.
*Data from Nooka.³

Safety of elranatamab^1-3

Safety data were deemed manageable by the researchers in all patient subgroups evaluated. Cytokine release syndrome (CRS) was the most common adverse event recorded across all MagnetisMM trials, with 87.3% of patients experiencing CRS in the non-BCMA differentiated population in MagnetisMM-1. Grade 3/4 CRS was exclusively observed in the BCMA-exposed population at 2.3%. Excluding CRS, the most frequently occurring adverse events were hematologic in all populations. Safety data are shown in Table 2.

Table 2. Adverse events*

Conclusion

The latest follow-up data from the MagnetisMM trials in combination support the further evaluation of elranatamab in patients with and without previous BCMA exposure. The findings also highlight patient subgroups that may achieve better responses, such as refractory (2–3 prior lines of therapy) patients in the naïve population and CAR T-cell therapy-treated patients in the exposed population. The differing study designs and participants make drawing direct comparisons between the MagnetisMM trials challenging, and comparisons should therefore be limited to equivalent subgroups within each trial.