Elranatamab improved PFS vs SOC combination therapy in relapsed/refractory multiple myeloma, meeting the primary end point of the MagnetisMM-5 trial.
Treatment with elranatamab-bcmm (Elrexfio) monotherapy led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with standard-of-care (SOC) daratumumab (Darzalex) plus pomalidomide (Pomalyst) and dexamethasone (DPd) in patients with relapsed/refractory multiple myeloma who received at least 1 prior line of therapy, meeting the primary end point of the phase 3 MagnetisMM-5 trial (NCT05020236).1
A news release from Pfizer stated that the majority of patients in the elranatamab arm remained progression free at the time of the prespecified interim analysis, with data exceeding the expected HR for PFS. Overall survival (OS) data remained immature at the time of this analysis.
Findings from MagnetisMM-5 will be shared with global health authorities and submitted for presentation at a future medical meeting.
“Effective intervention earlier in the course of disease represents a critical opportunity to improve outcomes for people living with multiple myeloma,” Jeff Legos, chief oncology officer at Pfizer, stated in a news release. “[Elranatamab] has already helped address a significant unmet need in heavily pretreated patients, delivering deep, durable, and clinically meaningful responses. The MagnetisMM-5 results reinforce our confidence in [elranatamab’s] potential to benefit patients earlier in their treatment journey and support our comprehensive strategy to evaluate [elranatamab] both as monotherapy and as part of combination approaches across multiple lines of therapy.”
In August 2023,
MagnetisMM-5 is an open-label, multicenter, randomized study enrolling patients at least 18 years of age with confirmed multiple myeloma per International Myeloma Working Group criteria who have measurable disease based on serum M-protein levels; urinary M-protein levels; or serum immunoglobulin free-light chain (FLC) levels and abnormal serum immunoglobulin kappa to lambda FLC ratio.3 Prior anti-myeloma therapy is required, which needs to include lenalidomide (Revlimid). An ECOG performance status of 2 or lower is also needed for enrollment.
The study is excluding patients with smoldering multiple myeloma, plasma cell leukemia, amyloidosis, or POEMS syndrome. Other key exclusion criteria comprised prior treatment with a BCMA-directed therapy, and stem cell transplant within 12 weeks of enrollment or active graft-vs-host disease.
The study comprised 2 parts. Part 1 was a safety lead-in, where patients treated with at least 3 prior lines of therapy received escalating doses of elranatamab in combination with daratumumab to identify the recommended dose for the combination in part 2.4 In part 2, patients who received between 1 and 4 prior lines of therapy were randomly assigned 1:1:1 to receive elranatamab monotherapy; elranatamab plus daratumumab; or DPd.
After assessing dose-limiting toxicities as the primary end point in part 1, PFS per blinded independent central review is the primary end point in part 2. Investigator-assessed PFS, PFS on subsequent therapy, OS, objective response rate, duration of response, complete response (CR) rate, duration of CR, time to response, minimal residual disease–negativity rate, safety, and quality of life are secondary end points in part 2.
