Dr Anderson on the FDA ODAC Decision Regarding Cilta-Cel in R/R Multiple Myeloma

Kenneth C. Anderson, MD, program director, Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute; Kraft Family Professor of Medicine, Harvard Medical School, discusses the March 15, 2024 FDA Oncologic Drugs Advisory Committee (ODAC) decision regarding the use of ciltacabtagene autoleucel (cilta-cel; Carvykti) in relapsed/refractory multiple myeloma.

The takeaway from the ODAC decision regarding cilta-cel in relapsed/refractory multiple myeloma was its endorsement for use in patients with lenalidomide (Revlimid)–refractory myeloma who had received only 1 prior line of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), Anderson begins. This decision was based on data from the phase 3 CARTITUDE-4 trial (NCT04181827), where cilta-cel demonstrated superior outcomes compared with standard-of-care therapies, he explains. The progression-free survival (PFS) data favored cilta-cel significantly, with a median PFS that was not reached in the cilta-cel arm vs 11.8 months (95% CI, 9.7-13.8) in the standard-of-care arm (HR, 0.26; 95% CI, 0.18-0.38; P < .001). The median overall survival (OS) was also not reached in either arm, but at 2 years, the OS rate was notably higher at 79% with cilta-cel vs 66% with standard of care, Anderson reports. These data also supported the April 5, 2024 FDA approval of the agent for the treatment of patients with relapsed/refractory disease who have received at least 1 prior line of therapy, including a PI and an IMiD, and are refractory to lenalidomide.

This ODAC decision is exciting as it recommends extending the use of cilta-cel to patients with disease that is relapsed/refractory to only 1 prior treatment, an indication that differs from the agent’s initial approval for heavily pretreated patients who had undergone at least 4 prior therapies, he expands. Notably, only a minority of patients in CARTITUDE-4 had been exposed to CD38 monoclonal antibodies as part of their initial treatment, contrasting with common practice in North America where daratumumab (Darzalez) is frequently used in initial regimens for both transplant-eligible and transplant-ineligible patients, Anderson states.

Despite the promising efficacy results in the trial, there were concerns about early deaths in the cilta-cel arm, he continues. Additionally, secondary cancers emerged as a concern, with similar secondary cancer incidence rates observed between the cilta-cel and standard-of-care arms, according to Anderson. In summary, the ODAC decision highlights the efficacy and endorsement of cilta-cel for use earlier in multiple myeloma disease course, providing a meaningful treatment option for patients with relapsed/refractory disease who have undergone limited prior therapies, he concludes.