Findings from the CARTITUDE clinical program found that ciltacabtagene autoleucel (cilta-cel), an anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy for multiple myeloma (MM), achieved high response rates and durable responses in patients with relapsed/refractory and earlier-stage disease. These findings will be featured at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting and the European Hematology Association (EHA) Virtual Congress.
Durable Response in Heavily Pre-treated MM
Safety and efficacy of cilta-cel was tested in the phase 1b/2 CARTITUDE-1 trial of 97 patients with relapsed/refractory MM. Patients had received a median of six prior lines of therapy and 42% were penta-refractory.
At a median follow-up of 18 months, most patients (98%) responded to treatment, including 80% who achieved a stringent complete response (sCR). Progression-free survival (PFS) at median follow-up was 66% (95% confidence interval [CI], 54.9–75.0) and overall survival (OS) was 81% (95% CI, 71.4–87.6). Results were comparable regardless of factors such as prior lines of therapy or cytogenetic risk. In patients with minimal residual disease (MRD) evaluations (n = 61), 92% achieved MRD negativity at a median one month post-infusion.
“What is remarkable about this study is that these patients, who had previously received multiple treatment regimens, have responded to cilta-cel without their disease progressing,” said Saad Z. Usmani, MD, of the Levine Cancer Institute, in a press release. “These compelling results, paired with the manageable safety profile and sustained efficacy, demonstrate the potential of cilta-cel for patients with relapsed and refractory MM.”
The most common hematologic adverse events (AEs) were neutropenia (96%), anemia (81%), thrombocytopenia (79%); leukopenia (62%); and lymphopenia (53%). Cytokine release syndrome (CRS) was observed in most patients (95%) and resolved in 99% of patients within 14 days of onset. Grade ≥3 neurotoxicity was observed in 10% of patients.
New Phase 2 Data from CARTITUDE-2
In addition to findings from CARTITUDE-1, the ASCO and EHA annual meetings will also feature presentations on new phase 2 data from a cohort from CARTITUDE-2 trial, which evaluated cilta-cel in earlier-phase MM.
The investigators evaluated 20 patients who had progressive MM, received one to three prior lines of therapy, and were refractory to lenalidomide. At a median follow-up of 5.8 months, the overall response rate was 95%, with three-quarters of patients achieving an sCR or a complete response. Neurotoxicity occurred in 20% of patients in this cohort (n = 4), which were generally manageable, according to the authors. No neurocognitive treatment-emergent AEs or grade ≥3 neurotoxicity have occurred.
“Our aim is to develop therapies that improve patient outcomes, and importantly in patients with heavily pretreated multiple myeloma who have no other options,” said Sen Zhuang, MD, PhD, Vice President of Clinical Research and Development at Janssen Research & Development, LLC, in a press release. “The results from the CARTITUDE clinical development program continue to show the promise of cilta-cel and support our efforts to bring this important treatment to patients in need in the near future.”
“With the possibility of achieving the progression-free survival reported and responses deepening as observed in the longer-term follow-up, I’m hopeful that cilta-cel will be part of the armamentarium in the future for patients in need of an additional treatment option,” said Dr. Usmani.