FDA Approves Ide-Cel for Relapsed/Refractory Multiple Myeloma
The FDA has approved idecabtagene vicleucel (ide-cel; formerly bb2121; Abecma) for the treatment of adult patients with relapsed or refractory multiple myeloma after 4 or more prior therapies, including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and an anti-CD38 antibody.1
Ide-cel represents the first B-cell maturation antigen (BCMA)–directed chimeric antigen receptor (CAR) T-cell therapy approved.
Approval for ide-cel is supported by findings from the pivotal phase 2 KarMMa trial (NCT03361748), the results of which were recently published in The New England Journal of Medicine.2 The trial showed that ide-cel led to deep and durable responses in patients with heavily pretreated multiple myeloma.
“In the KarMMa study, ide-cel elicited rapid responses in the majority of patients, and these deep and durable responses were observed in patients with triple-class exposed and refractory multiple myeloma. As a treating physician, I often work with patients with relapsed or refractory multiple myeloma who are in critical need of new therapies. Now, with the approval of ide-cel as the first anti-BCMA CAR T cell therapy, we are excited to finally be able to offer patients a new, effective personalized treatment option that is delivered through a single infusion,” said Nikhil C. Munshi, MD, associate director, The Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute, Boston, Massachusetts, in a statement.
A total of 140 patients who had received at least 3 prior treatment regimens for multiple myeloma including an IMiD, a PI, and an anti-CD38 antibody and were refractory to their last treatment regimen, were enrolled in the study. However, only 128 patients received infusion with ide-cel.
Patients were first treated with lymphodepleting chemotherapy of fludarabine (30 mg/m2/day) and cyclophosphamide (300 mg/m2/day) followed by 1 of 3 dose levels of ide-cel: 150 x 106 (n = 4), 300 × 106 (n = 70), or 450 × 106 (n = 54) CAR-positive T cells. Those who remained on the trial for 2 years were asked to continue on to a follow-up study (GC-LTFU-001; NCT03435796).
The primary outcome measure was overall response rate (ORR) by International Myeloma Working Group (IMWG) criteria as assessed by independent review committee, and secondary end points were complete response (CR) or better rate, time to response (TTR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), minimal residual disease (MRD), safety, pharmacokinetics, and immunogenicity.
At baseline, the median patient age was 61 years (range, 33-78) and patients had a median of 6 years (range, 1-18) since their diagnosis. A majority of the patients were male (59%), had high tumor burden (51%), BCMA expression ≥50% at screening (85%), ECOG performance status of 1 (53%), and Revised International Staging System disease stage of II (70%). Thirty-five percent of patients had high-risk features.
The median number of prior therapies was 6 (range, 3-16) and 94% had previously undergone at least 1 autologous hematopoietic stem cell transplant (94%). Eighty-eight percent of patients required bridging therapy. Eighty-nine percent of patients had double-refractory disease, 84% were triple-refractory, and 26% were penta-refractory.
Sixty-two patients were still on study treatment as of the data cutoff; overall, patients were followed for a median of 13.3 months (range, 0.2-21.2). The ORR by IMWG criteria was 73% (95% CI, 66%-81%; P < .001), and CRs or better were reported in 33%. At the lowest dose, the response rate was 50%, 69% responded at the second dose level, and 81% responded at the highest dose level.
Twenty-six percent of patients achieved MRD-negative status and 79% of the patients who achieved a CR or better were MRD negative.
Median TTR was 1.0 month (range, 0.5-8.8) and 2.8 months (range, 1.0-11.8) for a response of CR or better. The median DOR was 10.7 months (95% CI, 9.0-11.3) for all patients and 11.3 months (95% CI, 10.3-11.4) at the highest dose level. In patients with a CR or better, the median DOR was 19.0 months (95% CI, 11.3-not estimable [NE]).
Median PFS was 8.8 months (95% CI, 5.6-11.6) overall; among patients with a CR or better, the median PFS was 20.2 months (95% CI, 12.3-NE). The median OS was 19.4 months (95% CI, 18.2-NE) and at 12 months, the OS rate was 78%, although OS data are still immature.
All patients treated with ide-cel had an adverse event (AE) and 99% had a grade 3/4 event. The majority of events occurred within 8 weeks of infusion. Most grade 3/4 AEs were hematologic, including neutropenia in 89%, anemia in 60%, thrombocytopenia in 52%, leukopenia in 39%, lymphopenia in 27%, and febrile neutropenia in 16%. These events were considered to be in part due to lymphodepleting chemotherapy. Other frequent grade 3/4 AEs included hypophosphatemia in 16%, hypocalcemia in 8%, hyponatremia in 5%, and cytokine release syndrome (CRS) in 5%.
Among AEs of interest, there were 4 grade 3/4 bleeding events observed, infections of any grade were reported in 69% and were grade 3/4 in severity in 22%, CRS of any grade was reported in 84% and only 1 case was grade 5, and neurotoxicity was reported in 18% at any grade and at grade 3 in 3%.
Thirty-four percent of patients died during the study with most deaths due to complications of myeloma progression, although 2% died from treatment-related AEs of bronchopulmonary aspergillosis, gastrointestinal hemorrhage, and CRS within 8 weeks of infusion.
“CAR T cell therapies have shown transformational potential for the treatment of hematologic malignancies, and we, with our partners at bluebird bio, are proud to bring the first CAR T-cell therapy to appropriate triple-class exposed patients with relapsed or refractory multiple myeloma, offering the chance for durable response,” said Samit Hirawat, MD, chief medical officer, Bristol Myers Squibb, in a statement. “Bristol Myers Squibb is now the only company with 2 approved CAR T-cell therapies with distinct targets of CD19 and BCMA. As our second FDA-approved CAR T-cell therapy, Abecma underscores our commitment to deliver on the promise of cell therapies for patients who are battling aggressive and advanced blood cancers with limited effective treatment options.”
The recommended dose of ide-cel is a one-time infusion at a range of 300 to 460 x 106 CAR-positive T cells.
The label for ide-cel includes boxed warnings for CRS, neurologic toxicities hemophagocytic lymphohistiocytosis/macrophage activation syndrome, and prolonged cytopenia.
References
1. U.S. Food and Drug Administration Approves Bristol Myers Squibb’s and bluebird bio’s Abecma (idecabtagene vicleucel), the First Anti-BCMA CAR T Cell Therapy for Relapsed or Refractory Multiple Myeloma. News release. Bristol Myers Squibb. March 26, 2021. Accessed March 27, 2021. https://bit.ly/3m0V915
2. Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2021;384(8):705-716. doi:10.1056/NEJMoa2024850
Published at Sat, 27 Mar 2021 14:15:00 +0000