Elranatamab Achieves Positive Early Results in R/R Multiple Myeloma

Subcutaneous elranatamab (PF-06863135) appeared to elicit promising responses and a tolerable safety profile in patients with relapsed/refractory multiple myeloma, according to the results of the phase 1 MagnetisMM-1 study (NCT03269136).

Investigator-assessed responses per the International Myeloma Working Group (IMWG) criteria were observed starting at the 215 μg/kg dose (n = 20). At this dose level or above, a confirmed overall response rate (ORR) of 70% including a complete response (CR) or stringent CR rate of 30% was observed. The recommended phase 2 dose of 1000 μg/kg yielded an ORR of 83.3%, with 1 patient (16.7%) achieving a CR. The median time to response was 22 days (range, 21-50). Additionally, the probability of responders being event free at 6 months was 92.3% (95% CI, 56.7%-98.9%).

The dose-escalation study, which aimed to determine the safety and efficacy of the humanized BCMA-targeted bispecific monoclonal antibody, enrolled patients with relapsed/refractory multiple myeloma. Patients must have progressed on or be intolerant of established therapies including an immunomodulatory drug, a proteosome inhibitor, and an anti-CD38 monoclonal antibody. Additionally, patients were required to have measurable disease by IMWG criteria. Prior B-cell maturation antigen (BCMA)–directed therapy was also allowed.

Elranatamab was administered subcutaneously every week at 1 of several doses, including 80 μg/kg (n = 6), 130 μg/kg (n = 4), 215 μg/kg (n = 4), 360 μg/kg (n = 4), 600 μg/kg (n = 6), and 1000 μg/kg (n = 6). By the study’s data cutoff of February 4, 2021, 30 patients had undergone treatment with elranatamab.

Over half of patients enrolled on the study, the results of which were presented at the 2021 American Society of Clinical Oncology Annual Meeting, were female (56.7%) and the median age was 63.0 years (range, 46-80). Notably, 12% of patients were 65 years of age or older. The majority of patients had stage II disease (40.0%), followed by stage III (23.3%) and stage I (20.0%) disease.

Those enrolled had a median of 8.0 (range, 3-15) prior anti-myeloma therapies and 86.7% had disease that was triple refractory. Moreover, all patients enrolled had been treated with a proteasome inhibitor and immunomodulatory drug, and 96.7% had received an anti-CD38 therapy.

In terms of the additional doses, the 215 μg/kg dose yielded an ORR of 50.0% with 2 patients experiencing an sCR, 360 μg/kg yielded an ORR of 75.0% with 1 sCR, and the 600 μg/kg dose yielded an ORR of 66.7%, with 1 CR.

Among the 4 patients who received a prior BCMA-directed therapy, 3 achieved a response, including 1 sCR and 2 very good partial responses. Three patients were found to be negative for minimal residual disease. Additionally, among the 14 patients who achieved an IMWG-confirmed response, the median duration of response had not been reached.

In terms of safety, the most common any-grade hematologic adverse effects (AEs) included lymphopenia (83.3%) and anemia (60.0%); non-hematologic AEs included cytokine release syndrome (CRS; 73.3%), injection site reaction (50.0%), and nausea (36.7%). Grade 4 AEs included lymphopenia (63.3%), neutropenia (30.0%), thrombocytopenia (20.0%), and leukopenia (3.3%). Moreover, the most common grade 3 hematologic AEs included anemia (50%) and leukopenia (23.3%) and non-hematologic AEs included aspartate aminotransferase increase (10.0%) and alanine aminotransferase increase (10.0%).

Notably, patients were not given premedication or priming/set-up dosing to mitigate CRS, the incidence of which was 73.3% overall. CRS was limited to grade 1 and 2 events. Moreover, the median time to CRS onset was 1 day (range, 1-3) and lasted for a median duration of 3 days (range, 1-10). A total of 30% of patients were given tocilizumab (Actemra) and 10% were treated with steroids for CRS. CRS did not lead to treatment discontinuation, dose interruptions, or dose reductions.

Reference

Bahlis N, Raje NS, Costello C, et al. Efficacy and safety of elranatamab (PF-06863135), a B-cell maturation antigen (BCMA)-CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MM). J Clin Oncol. 2021;39(suppl 5):8006. doi:10.1200/JCO.2021.39.15_suppl.8006