At the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois, Binod Dhakal, MD, Medical College of Wisconsin, Milwaukee, Wisconsin, presented phase 3 results from CARTITUDE-4.

He presented on the use of ciltacabtagene autoleucel (cilta-cel), a dual-binding, BCMA-targeting CAR-T cell therapy, versus the standard of care therapy of pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd) in lenalidomide-refractory multiple myeloma (MM).

Transcript:

Hello, my name is Binod Dhakal. I'm from [the] Medical College of Wisconsin, Milwaukee. I'm [an] associate professor of medicine focusing on multiple myeloma. Here at ASCO 2023, I'm very excited to present the results from CARTITUDE-4, which is a phase 3 clinical trial evaluating ciltacabtagene autoleucel, or “cilta-cel”, versus 2 highly effective standard-of-care regimens in patients with lenalidomide-refractory multiple myeloma, after 1 to 3 prior lines of therapy.

The patients we included in the study are refractory to lenalidomide and have 1, 2, [or] 3 prior lines of therapy. This is the first CAR-T study to include patients after the first relapse. After meeting the eligibility criteria, the patients are randomized into either receiving cilta-cel or standard of care. Patients receiving cilta-cel underwent apheresis and bridging therapy with 1 or more cycles, lymphodepletion before receiving a cilta-cel infusion, whereas patients in the standard of care, received either DPd—that is daratumumab, pomalidomide, and dexamethasone— or PVd—that is pomalidomide, bortezomib, and dexamethasone. Again, based on physician's choice, till progression.

Patients in the cilta-cel arm while in the bridging therapy, received the same treatment DPd or PVd, as in standard care arm based on physician's choice. The primary endpoint of this study was progression-free survival (PFS), and we performed [a] number of other endpoints. For secondary endpoints, that included complete response or better overall response rate, MRD-negative disease, overall survival, and patient-reported outcomes. We also looked at the cilta-cel pharmacokinetics in patients receiving cilta-cel.

Our results showed that cilta-cel leads to significant improvement in response and in progression of death compared to standard of care by 74%. The hazard ratio was .26. The median progression-free survival in the cilta-cel arm was not reached at the median follow-up of 16 months versus 11.8 months in the standard of care arm. The 12-month PFS rate was 76% in the cilta-cel arm and 49% in the standard of care arm.

When looking at the specific subgroups, we saw that cilta-cel consistently prolonged progression-free survival, versus standard of care in all subgroups, including the key subgroups as patients with high-risk cytogenetics, triple class refractory disease, ISS stage 3 disease, and patients with soft tissue plasmacytomas. Cilta-cel also led to increased rates and depth of response, including higher MRD-negativity rates, compared to the standard of care.

In terms of safety, we saw the side effect profile [as] consistent with the non-profile of cilta-cel, Grade 3, 4 treatment-emergent adverse events occurred in almost all patients in both the arms, [and] were mostly hematologic and resolved by day 30. Looking at the CAR-T-specific adverse events, they were manageable with appropriate supportive care. More importantly, we saw lower incidence and severity of CAR-T-specific adverse events like cytokine release syndrome, [immune effector cell-associated neurotoxicity syndrome] (ICANS), or delayed neurotoxic toxicities like motor and neurocognitive events, much lower than patients with CARTITUDE-1, where patients treated with 3 or more prior lines of therapy.

In summary, our results show that compared to [the] standard of care, cilta-cel significantly extended progression-free survival in patients with lenalidomide-refractory [myeloma] and 1 to 3 prior lines of therapy. The hazard ratio was .26, which is one of the best hazard ratios ever observed in any randomized trials [of] myeloma in this setting. Cilta-cel also leads to increased rates and depth of response, and [the] use of cilta-cel in early lines may lead to improve tolerability.

All of this data is suggestive of the cilta-cel being a new standard of care [for] patients with lenalidomide-refractory myeloma, after the first relapse.
 

Source:

Dhakal B, Yong K, Harrison S, et al. First phase 3 results from CARTITUDE-4: Cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma. Presented at ASCO Annual Meeting; June 2-6, 2023; Chicago, IL. LBA106.