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

September 22, 2020

The FDA granted a Priority Review designation to idecabtagene vicleucel as treatment of adult patients with multiple myeloma who have received at least 3 prior therapies, including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody.

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.