Health Canada Approves Cilta-Cel for Relapsed/Lenalidomide-Refractory Myeloma

Health Canada has approved ciltacabtagene autoleucel (Carvykti; cilta-cel) for use in the treatment of adult patients with relapsed/refractory multiple myeloma who previously received 1 to 3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMID), and are refractory to lenalidomide.

This Notice of Compliance (NOC) marks cilta-cel as the first and only BCMA-targeted therapy that is approved for the treatment of patients with myeloma in the second line.

The regulatory decision is supported by results from the phase 3 CARTITUDE-4 trial (NCT04181827), in which, cilta-cel reduced the risk of disease progression or death by 74% compared with standard-of-care (SOC) treatment (HR, 0.26; 95% CI, 0.18-0.38; P < .0001) at a median follow-up of 15.9 months.

“The new approval for [cilta-cel] fills an important gap for patients with multiple myeloma who may require this therapy as early as first relapse and represents a significant milestone for Canadian patients with this disease,” Donna Reece, MD, chief medical officer of Canadian Myeloma Research Group, stated in a news release, “The first approval for cilta-cel was for its use in treating patients with refractory myeloma who had received at least 3 prior lines of therapy that included the 3 main drug classes [PIs, IMIDs, and anti-CD38 monoclonal antibodies]. However, myeloma treatment options have advanced rapidly, and Canadian patients with relapsed multiple myeloma may have received all these agents in second- or even first-line treatment, and yet have not qualified for cilta-cel—a highly effective immunotherapy that is transforming the treatment of multiple myeloma. This expanded indication will allow eligible patients with multiple myeloma to receive cilta-cel much earlier in their treatment journey.”

In the international, randomized, open-label CARTITUDE-4 trial, patients with relapsed/lenalidomide-refractory multiple myeloma were randomly assigned to receive cilta-cel (n = 208) vs a SOC regimen (n = 211), comprising either pomalidomide, bortezomib and dexamethasone (PVd; n =28) or daratumumab, pomalidomide and dexamethasone (DPd; n = 183). In the CAR T-cell therapy arm, all patients underwent leukapheresis and received bridging therapy.

At the 2024 International Myeloma Society Annual Meeting, investigators shared data from CARTITUDE-4showing that a single infusion of cilta-cel significantly extended overall survival in this patient population. The risk of death was reduced by 45% vs standard therapies.

Pyrexia, cytokine release syndrome, hypogammaglobulinemia, musculoskeletal pain, diarrhea, fatigue, upper respiratory tract infection, headache, hypotension, viral infection, and nausea were the most common nonlaboratory adverse effects observed among patients in CARTITUDE-4.

“The clinical trial showed that a single infusion of cilta-cel significantly lowered the risk of disease progression or death compared [with the] current SOC. This authorization means patients have a more effective treatment option that offers an opportunity for a deeper and durable response as early as their first relapse,” Richard LeBlanc, MD, added in the news release.

LeBlanc is a hematologist, medical oncologist, medical chief of the Clinical Immunology Laboratory, and head of the Multiple Myeloma Clinical Research Unit team; a clinical associate professor in the Department of Medicine at Université de Montréal; and the Myeloma Canada Chair on Multiple Myeloma.

Cilta-cel, which is a BCMA-directed, genetically modified autologous T-cell immunotherapy, previously received a NOC with conditions in February 2023 from Health Canada for the treatment of adult patients with multiple myeloma who have received at least 3 prior lines of therapy, including a PI, an IMID, and an anti-CD38 antibody, and are refractory to their last treatment.

Additionally, Canada’s Drug Agency recently recommended cilta-cel for reimbursement with conditions for eligible patients who have received 1 to 3 prior lines of therapy. According to the news release, Johnson & Johnson will continue working with the pan-Canadian Pharmaceutical Alliance to negotiate reimbursement for cilta-cel to enable public access.

“This milestone underscores our commitment to discovering and developing best-in-class therapies, particularly for incurable forms of cancer where patients face difficult prognoses,” Berkeley Vincent, president of Johnson & Johnson Innovative Medicine, Canada, emphasized. “Cilta-cel plays an important role in our work to redefine multiple myeloma and ultimately help patients achieve sustained remission. We are determined to get in front of cancer and these recent regulatory and access milestones for cilta-cel represent critical steps forward in reaching this goal.”

Reference

Health Canada authorizes CARVYKTI® (ciltacabtagene autoleucel) for patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy. News release. Biospace. November 22, 2024. Accessed November 26, 2024. https://www.biospace.com/press-releases/health-canada-authorizes-carvykti-ciltacabtagene-autoleucel-for-patients-with-relapsed-or-refractory-multiple-myeloma-who-have-received-one-to-three-prior-lines-of-therapy