Cilta-Cel Shows ‘Promising Efficacy, Safety’ in Newly Diagnosed MM

Ciltacabtagene autoleucel (cilta-cel) plus lenalidomide maintenance provides deep and durable responses with no new safety signals in patients with multiple myeloma (MM) who have had suboptimal response to frontline autologous hematopoietic stem cell transplantation (HSCT), according to results from the phase II CARTITUDE-2 study.

The study was led by Bertrand Arnulf, MD, PhD, of Saint-Louis Hospital in Paris, France, and presented at the Twelfth Annual Meeting of the Society of Hematologic Oncology.

The primary endpoint was measurable residual disease (MRD) negativity at 10^–5. Patients received cilta-cel infusion five to seven days after lymphodepletion initiation. Safety was assessed in the first five patients who received only cilta-cel. For up to two years afterward, 12 patients initiated continuous lenalidomide maintenance for at least 21 days after cilta-cel.

The median follow-up was 22 months. Twelve of 15 (80%) MRD-evaluable patients achieved MRD negativity, and the median time to MRD negativity was one month. Overall response rate and 18-month progression-free survival were both 94%.

All patients experienced grade 3 or 4 treatment-emergent adverse events (TEAEs) such as neutropenia (94%), lymphopenia (65%), thrombocytopenia (47%), leukopenia (41%), infection (71%), and cytokine release syndrome (CRS; 82%). The median time to CRS onset was eight days, and the median time to recovery was three days.

Grade 1 immune effector cell–associated neurotoxicity syndrome occurred in one patient, with a median time to onset of seven days and a median time to recovery of one day. Other neurotoxicities (all grade 3 or less) occurred in six patients, with a median time to onset of 21 days and a median time to recovery of 70 days. One case of secondary malignancy (grade 3 myelodysplastic syndrome) was not considered treatment related.

“In patients with [newly diagnosed] MM and [less than a complete response] after frontline [autologous HSCT], a cilta-cel infusion [plus] lenalidomide maintenance demonstrated deep and durable responses and no new safety signals, supporting promising efficacy and safety in this population,” the researchers concluded.

Reference

Arnulf B, Kerre T, Agha M, 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 #MM-505. Presented at the Twelfth Annual Meeting of the Society of Hematologic Oncology. September 4-7, 2024; Houston, Texas.