Elranatamab Shows PFS Benefit in Relapsed/Refractory Multiple Myeloma

Elranatamab (Elrexfio) demonstrated significantly better progression-free survival (PFS) compared with standard of care as monotherapy in adults with relapsed or refractory multiple myeloma (R/R MM) who had received at least 1 prior line of therapy, meeting its primary end point as assessed by blinded independent central review, according to topline results announced in a news release.¹

In the open-label, multicenter, randomized phase 3 MagnetisMM-5 study (NCT05020236), the B-cell maturation antigen (BCMA)-CD3 bispecific antibody was compared with daratumumab (Darzalex) plus pomalidomide (Pomalyst) and dexamethasone (DPd). No new safety signals were identified.

“[Elranatamab] has already helped address a significant unmet need in heavily pre‑treated patients, delivering deep, durable, and clinically meaningful responses,” Jeff Legos, PhD, MBA, chief oncology officer for Pfizer, stated in the news release. “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.”

Primary End Point Results

The PFS benefit observed at the prespecified interim analysis exceeded the target HR for efficacy, with most elranatamab-treated patients remaining free of progression at the time of the analysis. The detailed results will be submitted for presentation at a future medical congress. Overall survival, a key secondary end point, was not yet mature at the time of the interim analysis, and the trial remains ongoing to assess this outcome.

The comparator regimen of DPd represents an established standard of care for patients with R/R MM who have received prior lenalidomide and a proteasome inhibitor, making the head-to-head PFS superiority a clinically meaningful finding in this patient population.

Trial Design and Patient Population

MagnetisMM-5 is an open-label, multicenter, randomized phase 3 study that enrolled 497 patients across 26 countries. Eligible patients had received at least 1 prior line of treatment including lenalidomide (Revlimid) and a proteasome inhibitor. This double-class exposed population, having received both an immunomodulatory agent and a proteasome inhibitor, is a typical patient population in the RRMM landscape given the widespread use of these agents in frontline regimens.

Participants in the elranatamab arm received subcutaneous injections using a step-up priming dosing schedule: 2 step-up priming doses followed by a weekly 76 mg injection. Dosing frequency was adjusted to every 2 weeks after 24 weeks if a partial response was maintained for more than 2 months, and to every 4 weeks for all patients after 48 weeks on treatment. This extended-interval dosing schedule is designed to reduce patient burden over time while maintaining disease control. The trial’s secondary end points include objective response rate, complete response rate, duration of response, minimal residual disease negativity, and frequency of adverse events.²

Safety and Tolerability

The safety profile of elranatamab in MagnetisMM-5 was consistent with the drug’s known profile, and no new safety signals were identified. Elranatamab carries a boxed warning for cytokine release syndrome (CRS) and neurologic toxicity, which are class effects associated with BCMA-CD3 bispecific antibodies, necessitating step-up dosing and hospitalization for 48 hours after the first step-up dose and 24 hours after the second.³ The drug is available in the United States only through a Risk Evaluation and Mitigation Strategy program given these risks.

Other common treatment-related adverse events associated with elranatamab include fatigue, injection site reactions, diarrhea, musculoskeletal pain, decreased appetite, rash, cough, nausea, and fever. Decreased white blood cell, red blood cell, and platelet counts represent the most common severe laboratory abnormalities.

Current Approval Status and Clinical Context

Elranatamab is a subcutaneously delivered bispecific antibody that binds BCMA on myeloma cells and CD3 on T cells, activating cytotoxic T cells to kill myeloma cells. It is currently approved in more than 35 countries.¹ In the US, itreceived accelerated approval for adults with R/R MM who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. In the European Union, conditional marketing authorization was granted for patients who have received at least 3 prior therapies with disease progression on the last therapy.

The MagnetisMM-5 results, if confirmed in the final analysis, could support regulatory applications to extend elranatamab’s indication to earlier lines of therapy.

Broader Development Program

MagnetisMM-5 is part of a comprehensive elranatamab development program in double-class exposed patients. The fully recruited phase 3 MagnetisMM-32 study (NCT06152575) is designed to evaluate elranatamab in patients who previously received daratumumab as part of frontline multiple myeloma treatment, a population that is expected to grow substantially as anti-CD38 antibodies become increasingly standard in first-line regimens, creating a need for novel approaches at relapse that do not rely on daratumumab re-exposure. Other studies continue to evaluate elranatamab both as monotherapy and in combination regimens across multiple lines of therapy.

REFERENCES

1. Pfizer’s ELREXFIO significantly improves progression-free survival for double-class exposed patients with relapsed or refractory multiple myeloma. News release. Pfizer. April 29, 2026. Accessed April 29, 2026. https://tinyurl.com/mry8ux4k

2. A study to learn about the study medicine elranatamab alone and with daratumumab in people with multiple myeloma who have received other treatments (MAGNETISMM-5). ClinicalTrials.gov. Updated March 27, 2026. Accessed April 29, 2026. https://clinicaltrials.gov/study/NCT05020236

3. Elrexfio. Prescribing information. Pfizer; 2023. Accessed April 29, 2026. https://tinyurl.com/3zs5pexn