FDA approves Carvykti as second CAR T-cell therapy for advanced multiple myeloma
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The FDA approved ciltacabtagene autoleucel, a chimeric antigen receptor T-cell therapy for treatment of adults with relapsed or refractory multiple myeloma.
The indication applies to patients who received four or more previous lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.
Ciltacabtagene autoleucel (Carvykti; Janssen, Legend Biotech) — often called cilta-cel — is an autologous, gene-edited CAR T-cell therapy that targets the B-cell maturation antigen (BCMA) on the surface of cancer cells.
Cilta-cel is the second FDA-approved CAR-T cell therapy for adults with relapsed or refractory multiple myeloma. The FDA last year approved idecabtagene vicleucel (Abecma; Bristol Myers Squibb, bluebird bio) for the same indication.
The agency delayed its decision on cilta-cel last November so it could review additional information on an updated analytical method to evaluate the therapy.
The approval of cilta-cel should have a significant impact on clinical care for two reasons, according to Joshua P. Sasine, MD, PhD, assistant professor of medicine and director of the CAR-T program at Cedars-Sinai Cancer.
First, the efficacy of the treatment appears to be better than anything available for patients as a fourth line of therapy or later, he said.
“[Second], we are struggling to get the other commercially available CAR-T to patients given the supply chain limitations,” he told Healio. “This approval should allow for many more patients to receive CAR-T.”
Demand is “very high” among both patients with advanced multiple myeloma seeking the treatment and clinicians looking to refer patients, Sasine said.
“There is quite an appetite on both sides,” he said.
The manufacturing delays for idecabtagene vicleucel, also known as ide-cel, can be measured in terms of months for many patients, Sasine added.
“Despite being eligible, many patients will never receive CAR-T because of the limited supply,” he noted.
Sasine estimated that approximately 10% to 20% of patients with advanced multiple myeloma at his center who would have benefited from CAR-T ultimately have been able to receive the therapy. He said he hopes the approval of cilta-cel will increase the number of patients his center can treat, “although there is no guarantee [the manufacturer] won't also suffer from the same supply-chain constraints,” he said.
The FDA based approval of cilta-cel on data from the pivotal phase 1b/phase 2 CARTITUDE-1 trial.
The single-arm study included 97 patients (median age, 61 years; range, 43-78; 59% male; 71% white; 18% Black) with relapsed or refractory multiple myeloma who received at least three previous lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.
At median follow-up of 18 months, efficacy results showed an overall response rate of 98% (95% CI, 92.7-99.7) and a stringent complete response rate of 78% (95% CI, 68.8-86.1). Patients in the study achieved a median duration of response of 21.8 months.
Safety results showed cytokine release syndrome occurred among 95% of patients who received cilta-cel. Five percent of patients experienced grade 3 or higher CRS, with one case of grade 5 CRS reported.
Safety results showed an overall neurotoxicity rate of 26%, including 11 patients who had grade 3 or higher events. Twenty-three percent of patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS), including three patients (3%) who had grade 3 or grade 4 events and two patients (2%) with a grade 5 event.
“The responses in the CARTITUDE-1 study showed durability over time and resulted in the majority of heavily pretreated patients achieving deep responses after 18-month follow-up,” Sundar Jagannath, MD, principal study investigator and director of the Center of Excellence for Multiple Myeloma and professor of medicine, hematology and medical oncology at Tisch Cancer Institute at Icahn School of Medicine at Mount Sinai, said in a Janssen-issued press release. “The approval of cilta-cel provides physicians an immunotherapy treatment option that offers patients an opportunity to be free from anti-myeloma therapies for a period of time.”
Cilta-cel is comparable with ide-cel in terms of safety, Sasine said. However, cilta-cel has shown higher response rates and response duration during pivotal-phase testing.
“There are no randomized comparative trials between the two CAR-Ts but, among the single arm-trials, cilta-cel looks convincingly better from an efficacy standpoint,” he told Healio.
Cilta-cel will include a boxed warning that outlines risks for CRS, ICANS, Parkinsonism and Guillain-Barré syndrome, hemophagocytic lymphohistiocytosis/macrophage activation syndrome and prolonged and/or recurrent cytopenias associated with BCMA-directed CAR T-cell therapy. The FDA also is requiring the manufacturer to conduct a post-marketing observational study of patients treated with cilta-cel to comply with its Risk Evaluation and Mitigation Strategy monitoring program.
References:
Carvykti (prescribing information). Horsham, PA; Janssen Biotech; 2022.
Janssen. U.S. FDA Approves CARVYKT (ciltacabtagene autoleucel), Janssen’s first cell therapy, a BCMA-directed CAR-T Immunotherapy for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma. www.janssen.com/us-fda-approves-carvykti-ciltacabtagene-autoleucel-janssens-first-cell-therapy-bcma-directed-car-t. Published Feb. 28, 2022. Accessed March 1, 2022.
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