ODAC Casts 11 to 0 Vote in Favor of Cilta-Cel in R/R Multiple Myeloma

The FDA previously accepted a supplemental biologics license application (sBLA) for cilta-cel as a treatment for patients with relapsed/refractory multiple myeloma in June 2023.

The FDA Oncologic Drugs Advisory Committee (ODAC) cast a vote of 11 to 0 in support of the risk/benefit profile of ciltacabtagene autoleucel (cilta-cel; Carvykti) for patients with relapsed/refractory multiple myeloma who have received 1 prior line of therapy.¹

The FDA previously accepted a supplemental biologics license application (sBLA) for cilta-cel as a treatment for patients with relapsed/refractory multiple myeloma in June 2023.² Supporting data for the application came from the phase 3 CARTITUDE-4 trial (NCT04181827), which assessed cilta-cel vs pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (PVd), or daratumumab (Darzalex), pomalidomide, and dexamethasone (DPd) for patients who are refractory to lenalidomide (Revlimid).³

“I voted yes. The data from CARTITUDE-4 are still somewhat immature, but it appears to be favorable in its totality at this time. While the risk of early death, often before therapy, is not ignored in this discussion or this vote, it does seem to be outweighed by the long-term potential benefits here,” Ravi A. Madan, MD, chair of the ODAC, and program director of the Center for Cancer Research, said during the broadcast.¹

A total of 419 patients were randomly assigned to receive either cilta-cel (n = 208) or standard care (n = 211). In the standard of care (SOC) arm, 183 patients received DPd, and 28 received PVd. In the cilta-cel arm, 176 patients received study treatment vs 208 in the SOC arm.

A significantly lower risk of progression or death was observed in the cilta-cel arm vs SOC (HR, 0.26; 95% CI, 0.18-0.38; P <.001). In the cilta-cel group, the median duration of progression-free survival (PFS) was not reached vs 11.8 months (95% CI, 9.7-13.8) in the SOC arm. At 12 months, the PFS was 75.9% (95% CI, 69.4%-81.1%) vs 48.6% (95% CI, 41.5%-55.3%).

A complete response or better was observed in 73.1% of patients in the cilta-cel arm vs 21.8% in the SOC arm (risk ratio, 2.9; 95% CI, 2.3-3.7; P <.001; odds ratio,10.3; 95% CI, 6.5-16.4). The overall response rate was 84.6% for patients in the cilta-cel arm vs 67.3% in the SOC arm (risk ratio, 2.2; 95% CI, 1.5-3.1; P <.001; odds ratio, 3.0; 95% CI, 1.8-5.0). An ongoing response at 12 months was estimated to occur in 84.7% of patients in the cilta-cel arm vs 63.0% in the SOC arm.

In 60.6% of patients in the cilta-cel arm, minimal residual disease (MRD) negativity was observed vs 15.6% in the SOC arm (risk ratio, 2.2; 95% CI, 1.8-2.6; P <.001; odds ratio, 8.7; 95% CI, 5.4-13.9). Additionally, MRD negativity for patients with evaluable samples was observed in 87.5% vs 32.7%, respectively.

At the time of the analysis, overall survival (OS) data were still immature (HR, 0.78; 95% CI, 0.5-1.2; P = .26). The estimated OS rate at 12 months was 84.1% vs 83.6% in the cilta-cel and SOC arms, respectively. In the cilta-cel group, the median time to symptom worsening was 23.7 months (95% CI, 22.1-not estimable [NE]) vs 18.9 months (95% CI, 16.8-NE) in the SOC arm.

Regarding safety, grade 3/4 adverse effects (AEs) occurred in 96.6% of patients in the cilta-cel arm vs 94.2% in the SOC arm. Serious AEs occurred in 44.2% vs 38.9%. Secondary primary cancers occurred in 4.3% of patients in the cilta-cel arm vs 6.7% in the SOC group.

A total of 26.9% vs 24.5% of patients in each arm had grade 3/4 infections. A total of 39 patients died in the cilta-cel group vs 46 in the SOC group. Reasons for death included disease progressions (n = 14 vs 30) and AEs from treatment (n = 10 vs 5). Of note, 15 deaths in the cilta-cel group and 11 in the SOC group were from AEs not related to treatment.

Cytokine release syndrome occurred in 76.1% of patients who received cilta-cel. The median time to onset was 8 days, and the median duration was 3 days.

Patient characteristics in the cilta-cel and SOC arms, respectively, included having a median age of 61.5 years vs 61.0 years. Additionally, 55.8% vs 58.5% were male, and 75.5% vs 74.4% were White. In each arm, 54.8% vs 57.3% had an ECOG performance status of 0, 65.4% vs 62.6% had international staging system stage I disease, and 59.4% vs 62.9% had high-risk cytogenetics.

References

1. March 15, 2024 Meeting of the Oncologic Drugs Advisory Committee (ODAC). Streamed live March 15, 2024. Accessed March 15, 2024. https://shorturl.at/fmxz7
2. Janssen submits supplemental biologics license application to U.S. FDA seeking approval of CARVYKTI® for the earlier treatment of patients with relapsed or refractory multiple myeloma. News release. Janssen. June 6, 2023. Accessed March 15, 2024. bit.ly/3qA1Aig
3. San-Miguel J, Dhakal B, Yong K, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N Engl J Med. 2023;389(4):335-347. doi:10.1056/NEJMoa2303379