Cilta-Cel Emerges as a SOC in Lenalidomide-Refractory Multiple Myeloma

María-Victoria Mateos, MD, PhD

Ciltacabtagene autoleucel (cilta-cel; Carvykti) has solidified its status as a standard-of-care (SOC) treatment for patients with lenalidomide(Revlimid)-refractory multiple myeloma after 1 to 3 previous lines of therapy, according to María-Victoria Mateos, MD, PhD.

During the 51st Annual EBMT Meeting, Mateos presented updated data from the phase 3 CARTITUDE-4 trial (NCT04181827), which compared cilta-cel with SOC therapies in patients with lenalidomide-refractory multiple myeloma who received 1 to 3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD).1 At a median follow-up of 33.6 months (range, 0.1-45.0), patients who received the CAR T-cell therapy (n = 208) experienced a 45% reduction in the risk of death compared with those who received SOC agents (n = 211; HR, 0.55; 95% CI, 0.39-0.79; P = .0009). The 30-month overall survival (OS) rates were 76.4% and 63.8%, respectively.

“Cilta-cel is a new SOC for [patients with] relapsed/refractory multiple myeloma after 1 to 3 prior lines of therapy [who are] refractory to lenalidomide,” Mateos said in an interview with OncLive®. “There was a significant benefit in overall response rate and activity [in terms of] progression-free survival [PFS], but [there was a benefit] especially [regarding] OS. This is the first CAR T-cell therapy showing a benefit in OS in myeloma. The safety profile was acceptable and [patient] quality of life [QOL] was significantly improved [with cilta-cel].”

Prior data from CARTITUDE-4 supported the April 2024 FDA approval of cilta-cel for the treatment of adult patients with relapsed/refractory multiple myeloma who had received at least 1 prior therapy, including a PI and an IMiD, and who are refractory to lenalidomide.2

In the interview, Mateos, a consultant physician in the Hematology Department and an associate professor of medicine at the University of Salamanca in Spain, discussed the design of CARTITUDE-4, the clinical effect of the updated findings she presented, and future research avenues for cilta-cel in multiple myeloma.

OncLive: What were the key design features of CARTITUDE-4 and were there any notable differences in the baseline characteristics between the 2 arms?

Mateos: CARTITUDE-4 was a clinical trial conducted in [patients with] relapsed/refractory multiple myeloma after 1 to 3 prior lines of therapy. All patients had to be refractory to lenalidomide because this is a population with an unmet medical need. Most patients after just 1 prior line of therapy were refractory to lenalidomide. In this study, patients were randomly assigned 1:1 to receive a SOC therapy of either daratumumab [Darzalex] plus pomalidomide [Pomalyst] and dexamethasone [DPd] or pomalidomide plus bortezomib [Velcade] and dexamethasone [PVd], or cilta-cel following apheresis, bridging therapy with DPd or PVd, and lymphodepletion. The primary end point was PFS.

The baseline characteristics of the patients were quite comparable. The median number of prior lines of therapy [in both arms] was 2 [range, 1-3]. Approximately 25% of [all] patients were triple-class exposed, and [approximately] 15% were triple-class refractory.

What were the key efficacy data from the long-term update you shared during this year’s EBMT Meeting?

At a median follow-up of 33.6 months, there was a significant benefit in OS for [patients who received] cilta-cel vs SOC. Over 75% of patients in the cilta-cel arm remained alive at 33.6 months; the HR for OS was 0.55 [and was] sustained across the prespecified subgroups of patients. A benefit in PFS was also observed. The median PFS in the cilta-cel arm was not yet reached [NR] and the HR for PFS was 0.29 [95% CI, 0.22-0.39; P < .0001], indicating that the use of cilta-cel in patients [with relapsed/refractory multiple myeloma] after 1 to 3 prior lines of therapy reduced the risk of disease progression or death by 71%.

This benefit was also derived from the high complete response [CR] rate and stringent CR rate. [The] CR [or better] rate was 76.9% in the cilta-cel arm with a median duration of response that was NR [95% CI, not estimable (NE)-NE]. The minimal residual disease [MRD]–negativity rates [at a threshold of] 10-5 and 10-6 were also significantly higher for cilta-cel; approximately 60% of patients in the intention-to-treat population achieved MRD negativity status, with both sensitivity levels indicating that cilta-cel induced very deep responses.

Were there any new safety signals reported with cilta-cel?

At this follow-up, no new safety signals were reported. [Additionally], the QOL [data that were] reported throughout the time [period in terms of] new symptomatology were also significantly better for cilta-cel.

What are the next steps for the development of cilta-cel in multiple myeloma?

We have [now] reported the [updated] data from CARTITUDE-4 and this is a new SOC that is already approved by FDA and European Medicines Agency for patients with relapsed/refractory multiple myeloma after at least 1 prior line of therapy. The next step is to move [cilta-cel] to the first line of therapy. There are 2 ongoing phase 3 clinical studies evaluating the role of cilta-cel in the transplant-eligible population compared with autologous stem cell transplant, which is the SOC, and in the transplant-ineligible population compared with continuous therapy with lenalidomide, bortezomib, and dexamethasone followed by lenalidomide and dexamethasone.

[Moreover, with] cilta-cel combined with other strategies, such as BCMA- and GPRC5D-[targeted] bispecific monoclonal antibodies, we can [potentially] plan curative options for patients with standard-risk, newly diagnosed multiple myeloma. There are ongoing phase 2 clinical studies [examining] these curative approaches.

Disclosures: Mateos received honoraria from AbbVie, Amgen, BMS, GSK, Johnson & Johnson, Pfizer, Regeneron, Sanofi, and Stemline. She has participated in an advisory role for AbbVie, Amgen, BMS, GSK, Johnson & Johnson, Kite, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Stemline, and Takeda.

References

1. Mateos MV, San-Miguel J, Dhakal B, et al. Overall survival with ciltacabtagene autoleucel versus standard of care in lenalidomide-refractory multiple myeloma: phase 3 CARTITUDE-4 study update. Presented at: 51st Annual EBMT Meeting; March 30-April 2, 2025; Florence, Italy. Abstract OS14-02.
2. Carvykti is the first and only BCMA-targeted treatment approved by the US FDA for patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy. News release. Johnson & Johnson. April 5, 2024. Accessed April 7, 2025. https://www.jnj.com/media-center/press-releases/carvykti-is-the-first-and-only-bcma-targeted-treatment-approved-by-the-u-s-fda-for-patients-with-relapsed-or-refractory-multiple-myeloma-who-have-received-at-least-one-prior-line-of-therapy