Dr Delforge on the Rationale for CARTITUDE-4 in Lenalidomide-Refractory Myeloma

Michel Delforge, MD, PhD, professor, Faculty of Medicine, Department of Hematology, director, member, Leuven Cancer Institute, member, Senior Academic Staff, Council of the Faculty of Medicine, Council of the Department of Oncology, University Hospital Leuven, University of Leuven, discusses the background for conducting the phase 3 CARTITUDE-4 study (NCT04181827) in patients with lenalidomide (Revlimid)–refractory multiple myeloma. This investigation evaluated treatment with ciltacabtagene autoleucel (ciltacabtagene autoleucel; cilta-cel) compared with alternative approaches.

CARTITUDE-4 represents a pivotal study, as it was one of the first to investigate the effectiveness of a single infusion of a CAR T-cell therapy, cilta-cel, in comparison with standard of care (SOC) regimens for patients with relapsed or refractory multiple myeloma, Delforge begins. Typically, the SOC in this context involves combination therapies administered until disease progression occurs, he shares. Although many of these combination regimens demonstrate efficacy, the reality is that most patients will ultimately face disease relapse, along with the associated burden of ongoing treatment, Delforge states.

In the CARTITUDE-4 trial, cilta-cel was compared with 2 SOC regimens: one consisted of pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone, and the other included daratumumab (Darzalex), pomalidomide, and dexamethasone, Delforge expands. Patients in this study had previously undergone at least 1 line of therapy and were refractory to lenalidomide, he says. The primary findings indicated that cilta-cel exhibited clear superiority over SOC regimens concerning various efficacy measures, including overall response rate, complete response rate, andprogression-free survival, as well as, according to the latest update, a significant improvement in overall survival, Delforge reports.

However, it is essential to acknowledge the study’s limitations, particularly regarding indirect comparisons, which often come with inherent challenges, he continues. The scientific community tends to be cautious about relying on indirect comparisons, as they can sometimes be used to support conclusions that are not particularly strong, according to Delforge. In the case of CARTITUDE-4, the comparisons serve a confirmatory role, providing clear evidence rather than merely attempting to validate less compelling claims, Delforge concludes.

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Michel Delforge, MD, PhD, discusses the rationale for conducting the CARTITUDE-4 trial investigating cilta-cel in lenalidomide-refractory multiple myeloma.

Dr Delforge on the Efficacy of Cilta-Cel in Lenalidomide-Refractory Myeloma

Michel Delforge, MD, PhD, professor, Faculty of Medicine, Department of Hematology, director, member, Leuven Cancer Institute, member, Senior Academic Staff, Council of the Faculty of Medicine, Council of the Department of Oncology, University Hospital Leuven, University of Leuven, discusses the efficacy of ciltacabtagene autoleucel (ciltacabtagene autoleucel; cilta-cel) in the phase 3 CARTITUDE-4 study (NCT04181827) compared with alternative approaches for the treatment of patients with lenalidomide (Revlimid)–refractory multiple myeloma.

The analysis of cilta-cel in the CARTITUDE-4 trial indicates that the CAR T-cell therapy provides significantly greater clinical benefit for patients with lenalidomide-refractory multiple myeloma compared with alternative treatments derived from daratumumab (Darzalex)–focused clinical trials. Specifically, cilta-cel demonstrated superior efficacy across multiple outcomes, including overall response rate (ORR), very good partial response, complete response (CR), and progression-free survival (PFS). In the CARTITUDE-4 trial, cilta-cel reduced the risk of progression or death by 63% and generated a 73% reduction in real-world PFS vs the comparator regimens. Furthermore, the risk of next treatment or death was reduced by 72% with cilta-cel. All findings were statistically significant (

 < .0001), reinforcing cilta-cel’s potential as a leading therapeutic option for patients with relapsed and refractory multiple myeloma who have been previously treated with immunomodulatory agents and proteasome inhibitors, according to Delforge.

To ensure consistency with the CARTITUDE-4 patient population, adjustments were made to align the dataset with the trial’s inclusion criteria, Delforge reports, noting that this analysis revealed a remarkable and statistically significant advantage with cilta-cel in outcomes such as ORR and CR. Notably, the odds ratio for CR or better reached 16.45, underscoring the impressive efficacy of cilta-cel, he says. These findings demonstrate a highly significant advantage withcilta-cel over the comparator treatments, rather than a minor or moderate improvement, he emphasizes.

This strong PFS benefit with cilta-cel reinforces the positive results seen in CARTITUDE-4, he continues. Although the data do not yet reflect an overall survival benefit with cilta-cel, the compelling nature of these findings speaks to the clinical efficacy of the agent, Delforge explains. This indirect comparison underscores cilta-cel’s clear superiority over the various standard regimens typically used in relapsed settings, he concludes.

Michel Delforge, MD, PhD, discusses the efficacy of cilta-cel in CARTITUDE-4 vs alternative approaches for lenalidomide-refractory myeloma.

Michel Delforge, MD, PhD

Articles

Dr Delforge on the Rationale for CARTITUDE-4 in Lenalidomide-Refractory Myeloma

Dr Delforge on the Efficacy of Cilta-Cel in Lenalidomide-Refractory Myeloma