A single dose of ciltacabtagene autoleucel (cilta-cel), an investigational B-cell maturation antigen–directed CAR T-cell therapy, resulted in early, deep, and durable responses in heavily pretreated patients with relapsed or refractory multiple myeloma, according to updated results from the phase 1b/2 CARTITUDE-1 clinical trial. These findings were reported by Saad Zafar Usmani, MD, FACP, Director, Plasma Cell Disorder Program, and Director, Clinical Research in Hematologic Malignancies, Levine Cancer Institute, Charlotte, NC, at the ASCO 2021 virtual annual meeting.
“The efficacy results observed in heavily pretreated patients with multiple myeloma receiving cilta-cel are remarkable,” he said. “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.”
Dr Usmani presented updated data on 97 patients (median age, 61 years; 58.8% men) who had received a median of 6 prior treatment regimens (range, 3-18). All patients had been exposed to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody; 42.3% were penta-drug refractory, and 99% were refractory to their most recent line of therapy. A total of 19.6% of patients had plasmacytomas (13.4% extramedullary, 6.2% bone-based) and 23.7% had high-risk cytogenetics. All patients in the trial had received a single infusion of cilta-cel (target dose: 0.75 × 106 viable CAR-positive T-cells) 5 to 7 days following lymphodepletion.
At a median follow-up of 18 months, the overall response rate in patients treated with cilta-cel was 97.9% and the stringent complete response rate (sCR) was 80.4%. The median time to first response was 1 month and the median time to best response was 2.6 months. Nearly 95% of patients had at least a very good partial response to therapy.
“Median duration of response for the whole population was 21.8 months, and that for sCR patients has not been reached,” Dr Usmani said. “Response rates were comparable—in the range of 95% to 100%—across the different subgroups, including median previous lines of treatment, refractoriness, extramedullary plasmacytomas, and cytogenetic risk.”
Minimal residual disease (MRD) negativity for the overall study population was 57.7%. Among patients who achieved a complete response or better, MRD negativity was 89.4% for the MRD-evaluable patients and 43.3% for all patients in the study.
The 18-month progression-free survival rate was 66% among all patients and 75.9% among patients who had an sCR. The 18-month overall survival rate was 80.9% for all patients.
The safety profile of cilta-cel was manageable and consistent with its mechanism of action. Investigators did not observe any new safety signals with the longer follow-up. The most common any-grade hematologic adverse events (AEs) were neutropenia (95.9%), anemia (81.4%), thrombocytopenia (79.4%), leukopenia (61.9%), and lymphopenia (52.6%).
The majority of patients (N = 92) experienced cytokine release syndrome (CRS), a common CAR T-cell therapy–related AE. The median duration of CRS was 4 days and 99% of cases resolved within 14 days of onset.
Neurotoxicity of any grade was observed in 20.6% of patients, with grade ≥3 neurotoxicity observed in 10.3% of patients. Immune effector cell–associated neurotoxicity syndrome (ICANS) of any grade was reported in 16.5% of patients, with 2.1% being grade ≥3. All cases of ICANS occurred within a median of 8 days (range, 3-12 days) and resolved within a median of 4 days (range, 1-12 days).
Successful new patient management strategies were introduced within the CARTITUDE program to prevent and reduce the incidence of neurotoxicity. These included enhanced bridging therapy to reduce tumor burden, early and aggressive treatment of CRS and cell-associated neurotoxicity syndrome, and handwriting assessments and extended monitoring.
“At the CARTITUDE program level, over 100 additional patients have been dosed. The patient management strategies that have been introduced have been able to prevent and reduce these adverse events successfully in the ongoing cilta-cel studies,” Dr Usmani said.
Cilta-cel is under further investigation in other multiple myeloma populations in earlier lines of therapy as well as outpatient settings.