FDA Grants Priority Review to Ide-Cel for Relapsed/Refractory Multiple Myeloma

The FDA has granted a Priority Review designation to idecabtagene vicleucel (ide-cel; BB2121) as treatment of adult patients with multiple myeloma who have received at least 3 prior therapies, including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and an anti-CD38 antibody, announced Bristol Myers Squibb in a press release.¹

The Prescription Drug User Fee Act action date has been set as March 27, 2021. Ide-cel is an investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy.

“Today’s Priority Review milestone recognizes the potential of this first anti-BCMA CAR T-cell therapy to address a critical unmet need of patients with multiple myeloma,” said Stanley Frankel, MD, senior vice president, Cellular Therapy Development, Bristol Myers Squibb, in a statement. “We are pleased by the significant progress that is being made in partnership with patients and the multiple myeloma community to bring ide-cel to adults with relapsed and refractory multiple myeloma who are triple-class exposed and may benefit from an important new therapeutic option.”

The Biologics License Application (BLA) was submitted based on findings from the pivotal phase 2 KarMMa study, which evaluated the safety and efficacy of ide-cel in patients with heavily pretreated and highly refractory multiple myeloma. Findings from this study were recently presented during the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Meeting.²

In the open-label, single-arm, multicenter study, 128 adult patients with relapsed/refractory multiple myeloma who had received prior IMiD, PI, and anti-CD38 antibody therapy were evaluated and had a median age of 61 years (range, 33-78). Overall, 35% of the patients had high-risk cytogenetics, 45% had high tumor burden, 39% had extramedullary disease, and 85% had ≥50% tumor BCMA expression. The ECOG performance status was either 0 (45%), 1 (53%), or 2 (2%), and the R-ISS disease stage was I (11%), II (70%), or III (16%).

Patients received a median of 6 prior anti-myeloma therapies (range, 3-16), and 90% of patients had undergone a prior autologous stem cell transplant. Additionally, 94% of patients were refractory to anti-CD38 antibodies while 84% were triple-refractory.

The primary end point was objective response rate (ORR) by independent review committee, and secondary end points included complete response (CR) rate, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and quality of life.

The ORR was 73% (95% CI, 65.8%-81.1%; P <.0001), with a CR rate of 33% (95% CI, 24.7%-40.9%; P<.0001). The median time to CR was 2.8 months (range, 1-11.8), and the median DOR was 10.7 months.

The median PFS was 8.8 months (95% CI, 5.6-11.6). OS data were not yet mature, but the median OS was 19.4 months (95% CI, 18.2-not evaluable). The 12-month OS rate was 78%.

The majority of patients (84%) experienced cytokine release syndrome (CRS), and 78% of cases were grade 1/2. Grade 3 CRS was only observed in 5 patients while grades 4 and 5 occurred in 1 patient each. Neurotoxicity occurred in 18% of patients, but there were no cases of grade 4/5 neurotoxicity. Neutropenia was reported in 91% of patients, and grade 3 or higher cases were noted in 89% of patients. Thrombocytopenia occurred in 63%, of which grade 3 or higher cases occurred in 52%.

Three deaths were reported due to adverse events, including CRS, aspergillus pneumonia, and gastrointestinal hemorrhage. Five deaths were related to myeloma progression.

Ide-cel was previously granted a Breakthrough Therapy designation by the FDA, as well as a Priority Medicine (PRIME) designation and validation of its Marketing Authorization Application by the European Medicines Agency, for the treatment of relapsed/refractory multiple myeloma. Bristol Myers Squibb plans to submit ide-cel for additional markets outside of the United States and European Union. It is currently not approved for any indication.¹

“Today’s acceptance of the BLA for ide-cel for Priority Review by the FDA marks a key moment in our journey to bring this BCMA-directed CAR T-cell therapy to multiple myeloma patients who are in desperate need of new options,” said Joanne Smith-Farrell, PhD, chief operating officer oncology, bluebird bio, in a statement. “Based on the body of evidence we have generated in an advanced, heavily pretreated patient population, our confidence in the potential of ide-cel as an important treatment option remains high.”

_References

_{1. US Food and Drug Administration (FDA) accepts for priority review Bristol Myers Squibb and bluebird bio application for anti-BCMA CAR T cell therapy idecabtagene vicleucel (ide-cel, bb2121). News Release. Bristol Myers Squibb. September 22, 2020. Accessed September 22, 2020. https://bit.ly/3kDhakH}

_{2. Munshi NC, Anderson Jr LD, Jagannath S, et al. Idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma (RRMM): Initial KarMMa results. J Clin Oncol. 2020;38(suppl):8503.}