A Biologics License Application has been submitted to the FDA for the use of idecabtagene vicleucel for the treatment of adult patients with relapsed or refractory multiple myeloma
A Biologics License Application (BLA) has been submitted to the FDA for the use of idecabtagene vicleucel (ide-cel; bb2121) for the treatment of adult patients with relapsed or refractory multiple myeloma.1
An application was previously submitted to the FDA in March 2020 for ide-cel in a similar indication—specifically as treatment of patients with multiple myeloma who have received at least 3 prior therapies, which should include an immunomodulatory (IMiD) agent, a proteasome inhibitor (PI), and an anti-CD38 antibody.2 However, the FDA issued a Refusal to File letter to the developers, Bristol Myers Squibb and bluebird bio, noting that the Chemistry, Manufacturing, and Control (CMC) module of the BLA required more information. No other clinical or nonclinical data were requested.3
The new BLA includes further details on the CMC module to address the outstanding issues from the FDA’s Refusal to File letter.1
Ide-cel is an investigational B-cell maturation antigen (BCMA)–directed chimeric antigen receptor (CAR) T-cell therapy. Data supporting the potential approval for the CAR T-cell therapy in this setting come from the pivotal phase 2 KarMMa study, which were presented at the American Society of Clinical Oncology (ASCO) 2020 Virtual Scientific Program.4
KarMMa is an open-label, single-arm, multicenter study exploring the safety and efficacy of ide-cel in patients with relapsed or refractory multiple myeloma. Patients in the study had received at least 3 prior therapies including an IMiD, a PI, and an anti-CD38 antibody.
Among the 128 patients, the median age was 61 months (range, 33-78), 35% of patients had high-risk cytogenetics, 51% had a high tumor burden, 39% had extramedullary disease, and 85% had ≥50% tumor BCMA expression. ECOG performance status was 0 (45%), 1 (53%), or 2 (2%). R-ISS disease stage was I (11%), II (70%), or III (16%).
Patients had received a median of 6 (range, 3-16) prior antimyeloma regimens. Almost all patients (94%) had undergone a prior autologous stem cell transplant and 34% had received at least 1. Ninety-four percent of patients were refractory to anti-CD38 antibodies and 84% were triple refractory.
Ide-cel was administered at doses of 150 x 106 (n = 4), 300 x 106 (n = 70), or 450 x 106 (n = 54).
The primary end point was objective response rate (ORR) by independent review committee and secondary end points were complete response rate (CR), 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) and CRs were observed in 33% (95% CI, 24.7%-40.9%; P <.0001). The median time to CR was 2.8 months (range, 1-11.8). The median DOR was 10.7 months and the median PFS was 8.8 months (95% CI, 5.6-11.6).
Although the OS data were not yet mature, at the time of the ASCO analysis, the median OS was 19.4 months (95% CI, 18.2-not evaluable) and the 12-month OS rate was 78%.
Cytokine release syndrome (CRS) was reported in 84% of patients and 78% of cases were grade 1/2. Grade 3 CRS was observed in 5 patients, grade 4 in 1, and grade 5 in 1. Neurotoxicity was seen in 18% of patients, but there were no grade 4 or 5 cases. Neutropenia was reported in 91% of patients and grade ≥3 cases were observed in 89%. Thrombocytopenia was reported in 63% with grade ≥3 cases in 52%. Three deaths were reported due to adverse events of CRS, aspergillus pneumonia, and gastrointestinal hemorrhage, and 5 deaths were due to myeloma progression.
Ide-cel was previously granted an FDA breakthrough therapy designation for the indication. The CAR T-cell therapy also received a Priority Medicines designation from the European Medicines Agency.
Bristol Myers Squibb and bluebird bio Announce Submission of Biologics License Application (BLA) to FDA for Idecabtagene Vicleucel (Ide-cel, bb2121) for Adults with Relapsed and Refractory Multiple Myeloma. News release. Bristol Myers Squibb and bluebird bio. July 29, 2020. Accessed July 30, 2020. https://bwnews.pr/31dZ1SH
Bristol Myers Squibb and bluebird bio announce submission of biologics license application (bla) for anti-bcma car t cell therapy idecabtagene vicleucel (ide-cel, bb2121) to fda. News release. Bristol Myers Squibb. March 31, 2020. Accessed July 30, 2020 https://bit.ly/2JwKbxO
Bristol Myers Squibb and bluebird bio provide regulatory update on idecabtagene vicleucel (ide-cel, bb2121) for the treatment of patients with multiple myeloma. News release. Bristol Myers Squibb. May 13, 2020. Accessed July 30, 2020 https://bwnews.pr/3cpgJa1
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.