Dr Parrondo on the Use of Cilta-Cel in Lenalidomide-Refractory Multiple Myeloma

Ricardo D. Parrondo, MD, hematologist/oncologist, Mayo Clinic, discusses the implications of findings from the phase 3 CARTITUDE-4 trial (NCT04181827) of ciltacabtagene autoleucel (cilta-cel; Carvykti) in lenalidomide (Revlimid)–refractory multiple myeloma.

CARTITUDE-4 compared cilta-cel with standard-of-care (SOC) therapy in patients with lenalidomide-refractory multiple myeloma who had received between 1 and 3 prior lines of therapy. At a median follow-up of 15.9 months (range, 0.1-27.3), the median progression-free survival (PFS) was not reached in patients who received cilta-cel vs 11.8 months (95% CI, 9.7-13.8) in those who received standard pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (PVd) or daratumumab (Darzalex), pomalidomide, and dexamethasone (DPd; HR, 0.26; 95% CI, 0.18-0.38; P < .001). The 12-month PFS rates were 75.9% (95% CI, 69.4%-81.1%) and 48.6% (95% CI, 41.5%-55.3%) in the cilta-cel and SOC arms, respectively. Furthermore, the respective overall response rates in these arms were 84.6% and 67.3% (risk ratio, 2.2; 95% CI, 1.5-3.1; P < .001; odds ratio [OR], 3.0; 95% CI, 1.8-5.0), and the respective complete response rates were 73.1% and 21.8% (risk ratio, 2.9; 95% CI, 2.3-3.7; P < .001; OR, 10.3; 95% CI, 6.5-16.4).

Based on the CARTITUDE-4 data, the FDA granted priority review to a supplemental biologics license application seeking the approval of cilta-cel for this indication in 2023.

Using CAR T-cell therapy earlier on in the treatment course, particularly in lenalidomide-refractory patients who have received 1 to 3 prior lines of therapy, can elicit superior PFS outcomes compared with SOC regimens, such as PVd or DPd, Parrondo says. However, many patients continue to relapse even after receiving cilta-cel. Additional research is therefore needed to increase the efficacy of CAR T-cell therapy for patients with multiple myeloma, Parrondo explains.

Future research directions in this patient population may include combining CAR T-cell therapies with other myeloma agents or other CAR T-cell products, Parrondo notes. CAR T-cell therapy has demonstrated notable efficacy in patients with lymphoma, and the goal is to elicit similar remission rates and potentially increase cure rates with such regimens in myeloma, Parrondo concludes.