Elranatamab Approaches EU Approval for Heavily Pretreated Relapsed/Refractory Multiple Myeloma

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The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended the approval of elranatamab-bcmm for the treatment of adult patients with relapsed/refractory multiple myeloma who were previously treated with 3 or more lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody, and who experienced disease progression on their last therapy.

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of elranatamab-bcmm (Elrexfio) for the treatment of adult patients with relapsed/refractory multiple myeloma who were previously treated with 3 or more lines of therapy, including an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody, and who experienced disease progression on their last therapy.1

The positive opinion was supported by data from cohort A of the phase 2 MagnetisMM-3 study (NCT04649359), which showed that at a median follow-up of 14.7 months (range, 0.2-25.1), elranatamab produced a confirmed objective response rate (ORR) of 61% (95% CI, 51.8%-69.6%) among heavily pretreated patients who were naïve to BCMA-directed therapy (n = 123). Furthermore, 35% of patients experienced a complete response (CR) or better, and 56.1% experienced a very good partial response (VGPR) or better. The likelihood of patients maintaining this response at 15 months was 71.5% (95% CI, 58.8%-80.9%).2

Results from this study also confirmed the feasibility of transitioning responders to a once-every-other-week dosing regimen with elranatamab after 24 weeks of weekly administration. Eighty percent of responders (n = 50) who switched to the bi-weekly dosing schedule before the data cutoff of March 14, 2023, either maintained or improved their response for at least 6 months post-transition. Additionally, 38% of these patients achieved a CR or better after switching to this dosing scheme.1

Based on the CHMP recommendation, the European Commission is expected to make a final decision on the agent’s approval in the coming months.1

“We discovered and developed [elranatamab] as an off-the-shelf [ready-to-use] fixed-dose option with a subcutaneous administration to be broadly accessible as quickly as possible,” Chris Boshoff, chief oncology research and development officer and executive vice president at Pfizer, stated in a news release. “We’re excited at the possibility of [elranatamab] reaching people with multiple myeloma that have relapsed and refractory disease across Europe. We’re also exploring the use of [elranatamab] in earlier lines of therapy to potentially help even more people with multiple myeloma.”

In August 2023, the FDA granted accelerated approval to elranatamab for the treatment of adult patients with relapsed/refractory multiple myeloma who received 4 prior lines of therapy, including a PI, IMiD, and anti-CD38 monoclonal antibody.3 That regulatory decision was based on results from MagnetisMM-3.

MagnetisMM-3 was a multicenter, open-label, single-arm study that enrolled patients 18 years of age or older with a prior diagnosis of multiple myeloma. Other key eligibility criteria included measurable disease per International Myeloma Working Group criteria, an ECOG performance status of 2 or less, and adequate bone marrow, hepatic, and renal function. Patients were also required to be refractory to 1 or more PI, IMiD, and anti-CD38 antibody, and they must have been relapsed or refractory to their last antimyeloma regimen. In cohort A, prior BCMA-directed therapy was not allowed.2

A total of 123 patients across 47 study sites in 10 countries were enrolled in cohort A from February 9, 2021, to January 7, 2022. Patients were treated with 2 step-up priming doses of 12 mg and 32 mg of elranatamab on day 1 and day 4, respectively, during the first 28-day cycle. This was followed by 76 mg of subcutaneous elranatamab once per week for up to 6 cycles. Patients who achieved a PR or better after 6 treatment cycles switched to a dosing interval of once every 2 weeks.

The study’s primary end point was ORR by blinded independent central review (BICR). Secondary end points included ORR per BICR by extramedullary disease status, investigator-assessed ORR, CR rate, time to response, duration of response (DOR), duration of CR or better, minimal residual disease (MRD)–negativity rate, progression-free survival (PFS), overall survival (OS), safety, pharmacokinetics, and immunogenicity.

Additional findings revealed that 7.3% of responders were still on treatment and had not achieved a CR at the time of data analysis. Secondary end points of median DOR, PFS, and OS were not reached at the time of follow up; however, the 15-month rates were 71.5%, 50.9% and 56.7%, respectively.

Regarding safety, treatment-emergent adverse effects (TEAEs) were reported in all patients treated with elranatamab in cohort A (n = 123), with 70.7% experiencing grade 3 or 4 toxicities. The most common TEAEs included cytokine release syndrome (any-grade, 57.7%; grade ≥3, 0%), anemia (48.8%; 37.4%), and neutropenia (48.8%; 48.8%). Notably, grade 3/4 AEs decreased from 58.6% to 46.6% with the biweekly dosing schedule. Any-grade infections were reported in 69.9% of patients, including 39.8% who had grade 3 or 4 infections.

Moreover, TEAEs led to dose reductions in 28.5% of patients and dose interruptions in 77.2% of patients. A total of 44.7% patients died while on study, including 30.1% who died due to disease progression. Non-PD TEAEs led to death in 11.4% of patients (n = 14), 6.5% of which were due to infections (n = 8).

Elranatamab will continue to be evaluated as both a single agent and in combination with standard or novel therapies across multiple myeloma indications through the MagnetisMM clinical development program.1

“People with multiple myeloma are prone to relapse and resistance, and they often have no choice but to recycle treatment classes as they go through successive rounds of therapy. Efficacious and tolerable new treatments are desperately needed, especially in later-line care,” lead study investigator Mohamad Mohty, MD, PhD, professor of hematology and head of the Hematology and Cellular Therapy Department at the Saint-Antoine Hospital and Sorbonne University, Paris, France, said in a press release. “With its generally manageable safety profile and clinically meaningful and durable responses among hard-to-treat patients, [elranatamab] offers a new tool in the fight against relapse and resistance.” 

References

  1. Pfizer’s Elrexfio Receives Positive CHMP Opinion for Relapsed and Refractory Multiple Myeloma. News release. Pfizer. October 13, 2023. Accessed November 1, 2023. https://www.pfizer.com/news/announcements/pfizers-elrexfiotm-receives-positive-chmp-opinion-relapsed-and-refractory
  2. Lesokhin AM, Tomasson MH, Arnulf B, et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat Med. 2023;29(9):2259-2267. doi:10.1038/s41591-023-02528-9
  3. Pfizer's Elrexfio receives US FDA accelerated approval for relapsed or refractory multiple myeloma. News release. Pfizer. August 14, 2023. Accessed November 1, 2023. 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
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