The recommendation comes after positive phase 3 trial results in adult patients with relapsed and refractory multiple myeloma.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) announced the recommendation for approval of ciltacabtagene autoleucel (cilta-cel; Carvykti; Janssen Pharmaceutical) to treat relapsed and refractory multiple myeloma (RRMM). The recommended indication for this treatment is for adult patients with RRMM who have received at least 1 therapy prior to cilta-cel, such as an immunomodulatory agent (IMiD) or a proteasome inhibitor (PI); have presented disease progression on the previous therapy; and are refractory to lenalidomide.1
Cilta-cel is a CAR-T cell therapy that is directed against B-cell maturation antigen (BCMA), which is primarily visible on the surface of malignant multiple myeloma B-lineage cells in addition to late-stage B-cells and plasma cells. It previously received a conditional marketing authorization from the European Commission in May 2022 for adults with RRMM who received at least 3 prior therapies (eg, IMiD, PI, and anti-CD38 antibody) and demonstrated disease progression while on the last therapy. Cilta-cel is the first CAR-T cell therapy to receive a positive recommendation from the CHMP for the treatment of adult patients with RRMM and can be used as early as afte first relapse.1
“Early resistance to standard treatments is becoming more common in patients with lenalidomide-refractory multiple myeloma, highlighting a need for new options earlier in the course of treatment,” said Edmond Chan, MBChB, MD (Res), senior director, EMEA Therapeutic Area Lead Hematology, Janssen-Cilag Limited, in a press release. “Today’s recommendation from the CHMP recognizes the potential of cilta-cel to significantly improve outcomes for eligible patients with relapsed and refractory multiple myeloma, as early as after first relapse.”1
Trial Name: A Phase 3 Randomized Study Comparing JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA, Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Subjects With Relapsed and Lenalidomide-Refractory Multiple Myeloma.
ClinicalTrials.gov ID: NCT04181827
Sponsor: Janssen Research & Development, LLC
Completion Date (Estimated): June 30, 2027.
The recommendation made by the CHMP comes after supportive data from the CARTITUDE-4 study (NCT04181827). According to the investigators, this is the first randomized phase 3 trial to evaluate the efficacy and safety profile of cilta-cel compared with standard therapy—pomalidomide, bortezomib, and dexamethasone (PVd) or daratumab, pomalidomide, and dexamethasone (DPd)—in patients with relapsed and lenalidomide-refractory multiple myeloma who received at least 1 to 3 prior lines of therapy. The study, which will be conducted in 3 phases, includes screening (up to 28 days prior to randomization), treatment, and follow-up sections.1,2
The primary end point for the study is progression-free survival, with secondary end points including complete response rate (CR) or stringent complete response rate (sCR), overall minimal residual disease (MRD) negative rate, sustained MRD-negativity, MRD-negativity in patients with CR or sCR at 12 months follow-up, overall survival, and overall response rate (ORR). In addition, time to worsening symptoms were evaluated alongside quality of life from baseline.1,2
According to the results, patients who were treated with cilta-cel demonstrated a lower risk of disease progression or death compared to standard of care in patients with lenalidomide-refractory multiple myeloma. In addition, patients who were treated with cilta-cel had a stronger ORR (84.6% vs 67.3%, respectively), achieved CR or better (73.1% vs 21.8%, respectively), and had an absence of MRD (60.6% vs 15.6%, respectively).3
“We are committed to the advancement of cilta-cel and other immunotherapies, as we aim to improve outcomes for patients and redefine the multiple myeloma treatment paradigm,” said Sen Zhuang, MD, PhD, vice president of clinical research and development, Johnson & Johnson Innovative Medicine, in the press release. “Today’s milestone represents an important step forward in the treatment of this complex disease and in our ultimate goal of 1 day delivering a cure.”1
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