Cilta-cel improves outcomes in lenalidomide-refractory multiple myeloma

medwireNews: Treatment with ciltacabtagene autoleucel (cilta-cel) significantly extends progression-free survival (PFS) relative to standard of care in people with lenalidomide-refractory multiple myeloma who have received up to three prior lines of therapy, find the CARTITUDE-4 investigators. The dual-binding, BCMA-directed chimeric antigen receptor (CAR) T-cell therapy also achieved significantly higher response rates and depth of response, presenting author Hermann Einsele (Universitätsklinikum Würzburg, Germany) told the audience at the EHA2023 Hybrid Congress in Frankfurt, Germany. He added that “CAR T-specific adverse events were manageable with appropriate supportive care,” and therefore “cilta-cel has the potential to be a new standard of care for patients with lenalidomide-refractory myeloma after first relapse.” Outlining the background to the study, Einsele explained that cilta-cel treatment resulted in a median PFS of around 3 years in the phase 1b/2 CARTITUDE-1 study comprising patients with three or more prior lines of therapy. But as T-cell function and accordingly CAR T-cell activity “are clearly better in less heavily pretreated patients,” in CARTITUDE-4 “we aimed to test cilta-cel in earlier lines against effective standard of care treatments,” he continued. The randomized phase 3 trial included 419 patients who had received one to three prior treatments, including a proteasome inhibitor and an immunomodulatory drug. The 208 participants assigned to the experimental arm underwent apheresis, bridging therapy, and lymphodepletion before receiving a single infusion of cilta-cel at a target dose of 0.75x106 CAR T-cells/kg. The other 211 participants received physician’s choice of pomalidomide, bortezomib plus dexamethasone (PVd), or daratumumab, pomalidomide plus dexamethasone (DPd), which were also the regimens used in the bridging phase in the cilta-cel group. After a median follow-up of 15.9 months, median PFS was not reached in the cilta-cel arm and was 11.8 months in the standard of care arm, a significant difference equating to a 74% reduction in the risk for progression or death. The respective 12-month PFS rates were 76% and 49%. The investigator pointed out that during the bridging phase, when both groups of patients were receiving PVd or DPd, “there was a higher rate of progression in the arm that was going to receive cilta-cel.” The overall response rate was significantly higher among patients who received cilta-cel than those given standard of care, at 84.6% versus 67.3%, and so was the complete remission rate, at 73.1% versus 21.8%. The median duration of response was unreached and 16.6 months, respectively. Overall survival was immature at the time of data cutoff, but the hazard ratio for death of 0.78 favored cilta-cel, albeit without reaching statistical significance. Einsele noted that 32 patients assigned to the cilta-cel group did not receive the CAR T-cell therapy due to progression (n=30) or death (n=2) during the bridging phase. He therefore also reported the outcomes for the as-treated population (n=176), among whom the 12-month PFS rate (from apheresis) was 90%, the overall response rate was 99.4%, and the complete remission rate was 86.4%. With regard to treatment-emergent adverse events (TEAE), hematologic side effects were the most common in both groups, with cases of grade 3 or 4 occurring in 94.2% of patients in the cilta-cel arm and 86.1% of those in the standard of care arm. “Most high-grade cytopenias resolved to grade 2 or lower by day 30,” the presenter highlighted. Grade 3 or 4 infections were reported in a comparable 26.9% and 24.5% of the cilta-cel and control groups, respectively, while second primary malignancies developed in 4.3% and 6.7%. There were 10 deaths due to TEAEs among patients who received cilta-cel and five among those treated with the control regimen, of which seven and one were due to COVID-19, respectively. “When safety measures consistent with the international guidelines were introduced, there were no further COVID-19-related deaths in the cilta-cel arm,” said Einsele. He also presented data on CAR T-cell-specific AEs, noting that any-grade cytokine release syndrome, neurotoxicity, and immune effector cell-associated neurotoxicity syndrome occurred in 76.1%, 20.5%, and 4.5% of the as-treated patients, with events of grade 3 or 4 in 1.1%, 2.8%, and 0.0%. The “lower incidences and severity” of these AEs in CARTITUDE-4 versus CARTITUDE-1 suggests “improved tolerability of cilta-cel when used earlier in treatment,” concluded the researcher. These results were published simultaneously in The New England Journal of Medicine and presented previously at the 2023 ASCO Annual Meeting in Chicago, Illinois, USA. medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group EHA2023 Hybrid Congress; Frankfurt, Germany & Virtual: 8–15 June N Engl J Med 2023; doi:10.1056/NEJMoa2303379 2023 ASCO Annual Meeting; Chicago, Illinois, USA: 2–6 June

At a glance: The STEP trials

Springer Medicine

Cilta-cel improves outcomes in lenalidomide-refractory multiple myeloma

Related topics

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

At a glance: The STEP trials

Springer Medicine

Please log in to get access to this content

Related topics

Keynote webinar | Spotlight on antibody–drug conjugates in cancer