Dr Jagannath on the ODAC Meeting on the Safety of Cilta-Cel in R/R Multiple Myeloma

Sundar Jagannath, MBBS, director, Center of Excellence for Multiple Myeloma, professor, medicine (hematology and medical oncology), The Tisch Cancer Institute, Mount Sinai, discusses takeaways from the FDA’s Oncologic Drugs Advisory Committee (ODAC) Meeting on the safety considerations with ciltacabtagene autoleucel (cilta-cel; Carvykti) in patients with relapsed/refractory multiple myeloma.

At the ODAC Meeting, the committee voted 11 to 0 that the benefits of cilta-cel outweigh its risks for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory drug, and who are refractory to lenalidomide (Revlimid). Notably, data from the phase 3 CARTITUDE-4 trial (NCT04181827) spurred this conversation.

Jagannath begins by saying that in this trial, several patients who were randomly assigned to the control arm and received physician’s choice of standard-of-care (SOC) treatment experienced early disease progression and/or mortality, which raised questions. Specifically, it was noted that patients in the control arm may have been more likely to discontinue trial participation earlier than those in the cilta-cel arm due to awareness of not receiving the CAR T-cell therapy, leading to increased censoring of data in this group, according to Jagannath. This was attributed to the open-label nature of the study, potentially influencing patient decisions to withdraw from the study, he explains.

Furthermore, some patients who experienced disease progression on the control arm sought alternative treatments, including cilta-cel, which was already prepared for those who were randomly assigned to the CAR T-cell therapy arm, Jagannath emphasizes. Although initial outcomes with cilta-cel may appear concerning, survival rates in those who ultimately received the intended cilta-cel therapy were significantly improved over those in patients who received SOC, aligning with patterns seen with other complex medical interventions, he reports.

The consensus among the ODAC committee members was that the study design adequately demonstrated favorable progression-free survival and overall survival outcomes with cilta-cel vs SOC, Jagannath continues. They acknowledged the statistical end points defined by the study and recognized the impact of early events on trial outcomes. Ultimately, the committee felt confident in concluding that the studied drugs had successfully met their end points, he concludes.