The latest data from the CARTITUDE-2 cohort D were reported by Bertrand Arnulf, MD, PhD, of Hôpital Saint Louis and University Paris Cité in France, at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. He reported that, in patients with newly diagnosed multiple myeloma (NDMM) who achieved less than complete response (CR) after frontline autologous hematopoietic cell transplant (AHCT), a single infusion of ciltacabtagene autoleucel (cilta-cel) ± lenalidomide (len) maintenance resulted in deep and durable responses. Moreover, the associated treatment-emergent adverse events (TEAEs) were consistent with the known safety profile of cilta-cel.
Previous studies have demonstrated that cilta-cel, a B-cell maturation antigen-targeting chimeric antigen receptor (CAR) T-cell therapy, elicits deep and durable responses in heavily pretreated patients with relapsed or refractory MM. CARTITUDE-2 focused on patients with NDMM and a history of four to eight cycles of initial therapy, including induction, high-dose chemotherapy, and AHCT with or without consolidation. Dr. Arnulf reported that as of September 5, 2023 (median follow-up = 22 months), 17 patients received cilta-cel. Per protocol, the first five patients did not receive len maintenance after cita-cel, but the subsequent 12 patients did. Patients were a median age of 54 years; 6% had disease with high-risk cytogenetics; and 100% were International Staging System stage I at baseline. All patients had received prior immunomodulatory drugs and proteosome inhibitors.
“Overall response rate (ORR) was deep with cilta-cel,” Dr. Arnulf said, adding that the “response deepened over time and was durable.” Of the 15 measurable residual disease (MRD)-evaluable patients, 80% achieved MRD negativity at 10-5 with a median time to MRD negativity of one month. The ORR was 94%, and the median duration of response was not reached at the time of analysis. Progression-free survival and overall survival rates at 18 months were 94% each.
All patients had grade 3-4 TEAEs. Hematologic TEAEs included neutropenia (94%), lymphopenia (65%), thrombocytopenia (47%), and leukopenia (41%). One patient was diagnosed with prolonged cytopenia. Infections occurred in 71% of patients. The majority (82%) of patients experienced cytokine release syndrome (CRS) with a median time to onset of eight days. All CRS events were grade 1-2, and patients recovered in a median of three days. With regard to neurotoxicity, Dr. Arnulf said there were no cases of movement and neurocognitive TEAEs/parkinsonism. One patient did, however, experience immune effector cell-associated neurotoxicity syndrome with an onset of seven days and one day for recovery. Other neurotoxicities occurred in six patients with a median time to onset of 21 days and a median time to recovery of 70 days. One patient had a secondary malignancy of grade 3 myelodysplastic syndromes with an onset of 353 days that the investigators determined to not be related to treatment.
CAR T cells peaked in the blood at a median of 12 days post-infusion and remained detectable for a median of 43 days. Dr. Arnulf said that although CAR-T expansion was high, persistence was lower than that seen in previous studies. “I think we have much to learn to have an explanation,” he added.
Dr. Arnulf concluded his presentation by stating the new data reveal promising efficacy and safety of cilta-cel ± len maintenance in patients with NDMM who achieved less than a CR following AHCT frontline treatment.
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
Arnulf B, Kerre T, Agha ME, et al. Efficacy and safety of ciltacabtagene autoleucel ± lenalidomide maintenance in newly diagnosed multiple myeloma with suboptimal response to frontline autologous stem cell transplant: CARTITUDE-2 cohort D. Abstract 7505. Presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting; June 3, 2024; Chicago, Illinois.
