HRQOL Improved With Cilta-Cel in Lenalidomide-Refractory Multiple Myeloma

Patient-reported outcomes from CARTITUDE-4 showed a median time to sustained worsening of symptoms of 23.7 months with cilta-cel and 18.9 months with standard of care.

Patient-reported outcomes demonstrated that ciltacabtagene autoleucel (cilta-cel; Carvykti), when compared with standard of care, led to health-related quality of life (HRQOL) improvements as well as delayed symptom worsening in patients with relapsed, lenalidomide (Revlimid)-refractory multiple myeloma, according to results from the phase 3 CARTITUDE-4 trial (NCT04181827) published in Lancet Haematology.

At a median follow-up of 15.9 months (IQR, 12.4-17.8), the Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) compliance post-baseline score was 70% to 81% for patients who received cilta-cel and 79% to 89% for patients who received standard of care; the MySIm-Q median time to sustained worsening of symptoms was 23.7 months with cilta-cel and 18.9 months with standard of care (HR, 0.42; 95% CI, 0.26-0.68; P = .0003).

European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core C30 (EORTC QLQ-C30) global health status (GHS) 12-month score mean changes were +10.1 points (95% CI, 7.0-13.1) for cilta-cel and −1.5 points (95% CI, −5.3 to 2.3) for standard of care; for EuroQol 5-Dimension 5-Level (EQ-5D-5L) visual analogue scale mean changes were +8.0 (95% CI, 5.2-10.7) and +1.4 (95% CI, −1.9 to 4.7), respectively.

“In CARTITUDE-4, cilta-cel provided greater improvements than standard of care in overall HRQOL, including multiple functional domains and patient-reported pain and fatigue, in patients with lenalidomide-refractory multiple myeloma after 1 to 3 previous lines of therapy,” Roberto Mina, MD, at the University of Turn, and author of the study, and fellow authors, stated. “Improvements were sustained until at least month 12 and encompassed overall health status, functioning, and multiple myeloma-specific symptoms including pain and fatigue.”

A total of 419 patients were randomly assigned, in a 1:1 ratio, to receive cilta-cel (n = 208) or standard of care (n = 211). Those in the cilta-cel arm underwent apheresis, 1 or more cycles of bridging therapy depending on clinical status and cilta-cel manufacturing time, and lymphodepletion consisting of 300 mg/m2 cyclophosphamide and 30 mg/m2 fludarabine daily for 3 days. Then, 5 to 7 days after lymphodepletion, patients were given a single cilta-cel infusion at a target dose of 0.75x106 CAR-T cells/kg. Standard of care was either 1800 mg of subcutaneous daratumumab (Darzalex), 4 mg of oral pomalidomide (Pomalyst), and 40 mg of oral or intravenous dexamethasone in 28-day cycles (n = 182), or 4 mg of oral pomalidomide, 1.3 mg/m2 of subcutaneous bortezomib (Velcade), and 40 mg of oral dexamethasone in 21-day cycles (n = 26).

To be included in the study, patients needed to be lenalidomide-refractory or relapsed/refractory multiple myeloma who received 1 to 3 prior lines of therapy with a proteasome inhibitor and an immunomodulatory drug, as well as an ECOG performance status of 0 or 1. Those who received prior CAR T-cell or anti-BCMA therapies were not permitted enrollment.

Clinical efficacy was previously reported with progression-free survival (PFS) as the primary end point, however, time to sustained worsening of patient-reported symptoms, change from baseline in the MySIm-Q, the EORTC QLQ-C30, and the EQ-5D-5L, were key secondary end points.

The median time to improvement on the MySIm-Q total symptom scale was 2.8 months (IQR, 0.3-6.2) for cilta-cel and 1.7 months (IQR, 1.2-3.0) for standard of care; on the total impact scale, it was 2.8 months (IQR, 0.4-6.5) and 1.4 months (IQR, 1.1-3.0). At month 12, 35% of the cilta-cel group and 14% of the standard of care group achieved clinically meaningful improvements in total multiple myeloma score compared with 11% and 33%, respectively, who achieved worse scores.

EORTC QLQ-C30 physical functioning, role functioning, and social functioning were all improved in the cilta-cel group, though they were not improved in the standard of care group.

In the cilta-cel group, EQ-5D-5L visual analogue scale scores fell from baseline to month 3, then increased over time to a least-squares mean of +8.0 points (95% CI, 5.2-10.7) at month 12 compared with a +1.4-point increase in the standard of care group. Results were similar at 18 months.

At the median follow-up of 15.9 months (IQR, 12.4-17.8), the primary analysis from the CARTITUDE-4 trial showed that cilta-cel “significantly improved” PFS over standard of care (HR, 0.26; 95% CI, 0.18-0.38; P <.001), increased the overall response rate (ORR; 85% vs 67%, respectively), depth of response (73% vs 22%), and rate of minimal residual disease negativity (61% vs 16%).

“With previously reported data showing that cilta-cel significantly improves PFS, ORR, and depth of response vs standard of care, the improvements in HRQOL that we observed support the use of cilta-cel in earlier lines of treatment for lenalidomide-refractory multiple myeloma,” the authors concluded.

Reference

Mina R, Mylin AK, Yokoyama H, et al. Patient-reported outcomes following ciltacabtagene autoleucel or standard of care in patients with lenalidomide-refractory multiple myeloma (CARTITUDE-4): results from a randomised, open-label, phase 3 trial. Lancet Haematol. 2025;12(1):e45-e56. doi:10.1016/S2352-3026(24)00320-X