Elranatamab Meets Phase 3 PFS End Point in R/R Myeloma After Anti-CD38 Therapy and Lenalidomide

Treatment with elranatamab-bcmm (Elrexfio) monotherapy yielded a statistically significant and clinically meaningful reduction in the risk of disease progression or death vs investigator's choice of standard regimens in patients with relapsed/refractory multiple myeloma who received at least 1 prior line of therapy including an anti-CD38 antibody and lenalidomide (Revlimid), meeting the primary end point of progression-free survival (PFS) in the phase 3 MagnetisMM-32 trial (NCT06152575).¹

The comparator regimens comprised elotuzumab (Empliciti), pomalidomide (Pomalyst), and dexamethasone (EloPd); pomalidomide, bortezomib (Velcade), and dexamethasone (PVd); or carfilzomib (Kyprolis) and dexamethasone (Kd).

At the prespecified interim analysis for efficacy, PFS was assessed by blinded independent central review (BICR). Topline findings announced by Pfizer showed that more than 75% of patients treated in the elranatamab arm had not experienced disease progression or death from any cause at the time of the analysis, and the estimated 18-month PFS rate in the experimental group was 68%; the median PFS had not been reached. Data for overall survival (OS), a key secondary end point, remain immature, and follow-up will continue to the next prespecified OS analysis.

Safety data for elranatamab were consistent with its known profile, and no new safety signals were identified. Infection prophylaxis measures were instituted from the start of the study. Grade 3 or higher infections occurred in 27.5% of patients in the elranatamab arm vs 18.1% of patients in the investigator's choice arm, and grade 5 infections occurred at rates of 0.8% and 1.6%, respectively.

Pfizer plans to submit the data to global health authorities, and detailed results will be shared at a future medical meeting and submitted for publication.

"The MagnetisMM-32 results are particularly compelling given the rigorous and clinically relevant benchmark of 3 established standard-of-care regimens. Demonstrating a significant PFS benefit against this active control highlights the potential of elranatamab to provide an important treatment option for patients whose disease has progressed following anti-CD38 therapy and lenalidomide," C. Ola Landgren, MD, PhD, professor of medicine, chief of the Myeloma Division, and director of the Sylvester Myeloma Institute at the University of Miami Miller School of Medicine, stated in a news release.

In August 2023, the FDA granted accelerated approval to elranatamab for the treatment of adult patients with relapsed/refractory multiple myeloma who have previously received at least 4 lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody.² This prior approval was supported by data from the phase 2 MagnetisMM-3 trial (NCT04649359).

How was MagnetisMM-32 designed?

MagnetisMM-32 was an open-label, multicenter, randomized phase 3 trial that enrolled 523 patients across 26 countries.¹ Eligible patients needed to be at least 18 years of age with multiple myeloma per International Myeloma Working Group criteria who received 1 to 4 prior lines of therapy including an anti-CD38 antibody, such as daratumumab (Darzalex) or isatuximab-irfc (Sarclisa), and lenalidomide.³ Documented disease progression on, or failure to respond to, the last line of therapy was required. Other key inclusion criteria comprised measurable disease and an ECOG performance status of 2 or lower.

Patients were excluded if they received prior BCMA-directed or CD3-redirecting therapy; had plasma cell leukemia; had known central nervous system involvement; or underwent stem cell transplant within 12 weeks of enrollment.

Patients were randomly assigned to receive elranatamab monotherapy or investigator's choice of EloPd, PVd, or Kd. Elranatamab was administered subcutaneously as 2 step-up priming doses followed by weekly doses in 28-day cycles, with a transition to dosing every 2 weeks and then monthly.¹

The primary end point was PFS by BICR, and the key secondary end point was OS.^1,3 Additional secondary end points include PFS on next-line treatment, objective response rate, duration of response, very good partial response or better rate, complete response rate, minimal residual disease negativity rate, safety, and health-related quality of life.³

“The treatment landscape for multiple myeloma continues to evolve as anti-CD38–based regimens and lenalidomide are increasingly used earlier in care. Yet many patients ultimately experience disease progression, with limited treatment options available following these commonly used therapies. MagnetisMM-32 demonstrates that [elranatamab], an off-the-shelf, fixed-dose monotherapy, delivers a significant and clinically meaningful PFS benefit and an encouraging safety profile in this increasingly important treatment setting, with median PFS not yet reached and a high percentage of patients remaining progression-free at the time of analysis,” Jeff Legos, PhD, MBA, chief oncology officer at Pfizer, added in a news release.¹ “These findings further strengthen the rationale for moving BCMA-directed therapy earlier in the treatment journey and underscore Elrexfio's potential to help redefine outcomes for patients.”

References

1. Pfizer's Elrexfio outperforms standard regimens and meets primary endpoint in phase 3 study in relapsed or refractory multiple myeloma. News release. Pfizer. October 27, 2026. Accessed October 27, 2026. https://www.pfizer.com/news/press-release/press-release-detail/pfizers-elrexfio-outperforms-standard-regimens-and-meets
2. Pfizer's Elrexfio receives US FDA accelerated approval for relapsed or refractory multiple myeloma. News release. Pfizer. August 14, 2023. Accessed October 27, 20236 https://investors.pfizer.com/Investors/News/news-details/2023/Pfizers-ELREXFIO-Receives-U.S.-FDA-Accelerated-Approval-for-Relapsed-or-Refractory-Multiple-Myeloma/default.aspx
3. MagnetisMM-32: a study to learn about the study medicine called elranatamab in people with multiple myeloma (MM) that has come back after taking other treatments (including prior treatment with an anti-CD38 antibody and lenalidomide). ClinicalTrials.gov. Updated August 24, 2026. Accessed October 27, 2026. https://clinicaltrials.gov/study/NCT06152575