FDA Grants Breakthrough Therapy Designation to Elranatamab for Relapsed/Refractory Multiple Myeloma

The FDA has granted a breakthrough therapy designation to elranatamab for the treatment of patients with relapsed/refractory multiple myeloma.

The FDA has granted a breakthrough therapy designation to elranatamab (PF-06863135) for the treatment of patients with relapsed/refractory multiple myeloma, according to an announcement from Pfizer.1

The designation is based on 6-month follow-up data from cohort A (n = 123) of the phase 2 MagnetisMM-3 trial (NCT04649359). At a median follow-up of 6.8 months, the overall response rate (ORR) was 61.0%. Among responders, there was 90.4% likelihood of maintaining a response for at least 6 months.

“The FDA’s breakthrough designation recognizes the potential of elranatamab as an innovative medicine for people with multiple myeloma whose disease has relapsed or is refractory to existing treatments, which at present leaves very few avenues for staving off this currently incurable cancer,” Chris Boshoff, MD, PhD, chief development officer of Oncology and Rare Disease, Pfizer Global Product Development, said in a press release. “This marks Pfizer’s twelfth FDA breakthrough therapy designation in oncology, a testament to our relentless commitment to developing transformational cancer medicines in areas of high unmet need. We look forward to working with the FDA to accelerate the development of this therapy.”

Elranatamab is a BCMA- and CD3-directed bispecific antibody that has received both orphan drug designation and fast track designation from the FDA for the treatment of patients with relapsed/refractory multiple myeloma. The agent, which is administered subcutaneously, offers an ideal alternative to intravenous administration, and may reduce the risk of potential adverse effects, such as cytokine release syndrome (CRS).

MagnetisMM-3 is an open-label, multicenter, single-arm, phase 2 study evaluating the safety and efficacy of elranatamab monotherapy in patients with relapsed/refractory multiple myeloma in 2 cohorts. In cohort A, patients have not received prior BCMA-directed therapy, and in cohort B, prior BCMA-directed therapy is required.2

In addition, patients must be refractory to at least one immunomodulatory drug, 1 proteasome inhibitor, and 1 anti-CD38 antibody, be refractory to the last anti-myeloma treatment, and have measurable disease, an ECOG performance status of 2 or less, and resolved acute effects of any prior therapy to baseline severity or grade 1 or lower.

Patients will be excluded from enrollment if they have received a diagnosis of smoldering myeloma, active plasma cell leukemia, amyloidosis, or POEMS syndrome, or have undergone stem cell transplant within 12 weeks prior to enrollment.

Patients are receiving subcutaneous elranatamab at a dose of 76 mg every week with a 2-step-up priming dose regimen administered during the first week of treatment.

The primary end point is ORR, and key secondary end points include ORR by baseline extramedullary disease status, duration of response, complete response rate, progression-free survival, overall survival, minimal residual disease negativity rate, and frequency of treatment-emergent adverse effects (TRAEs).

The study showed that treatment with elranatamab was associated with a manageable safety profile. The most common TEAE regardless of causality was CRS (57.9%). Additionally, most events were low grade (grade 1, 43.2%; grade 2, 14.2%).

Updated data from MagnetisMM-3 will be presented at the 2022 ASH Annual Meeting and Exposition, taking place December 10 to 13, 2022, in New Orleans, Louisiana.


  1. Pfizer’s elranatamab granted FDA breakthrough therapy designation for relapsed or refractory multiple myeloma. News release. Pfizer Inc. November 3, 2022. Accessed November 3, 2022. https://bit.ly/3T20rbE
  2. MagnetisMM-3: study of elranatamab (PF-06863135) monotherapy in participants with multiple myeloma who are refractory to at least one PI, one IMiD, and one anti-CD38 mAb. ClinicalTrials.gov. Updated October 5, 2022. Accessed November 3, 2022. https://clinicaltrials.gov/ct2/show/NCT04649359