A post hoc subgroup analysis of CARTITUDE-4 trial demonstrated that ciltacabtagene autoleucel (cilta-cel) improved outcomes for patients with lenalidomide-refractory functional high-risk multiple myeloma (MM) after 1 prior line of therapy vs standard of care treatment.  

These results were presented by Luciano Costa, MD, University of Alabama at Birmingham, Birmingham, Alabama at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. 

Transcript:

Hi, my name is Luciano Costa. I'm a professor of medicine and director of the Myeloma Program at the University of Alabama at Birmingham. I'm here at ASCO 2024, presenting on behalf of the investigators for the CARTITUDE-4 trial, the results of that trial for a subgroup of patients with 1 prior line of therapy, particularly the patients with functional high-risk disease.

As many of you know, CARTITUDE-4 was a very important trial that enrolled patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy, who have disease that had been exposed to a proteasome inhibitor and exposed in refractory to lenalidomide, and randomized those patients between a control arm where patients receive a standard of care regimen, which was dara-pom-dex [daratumumab plus pomalidomide and dexamethasone] for the majority of patients, but they also had the option of pomalidomide bortezomibdexamethasone, or to receive that same regimen as a bridging therapy leading to an infusion of cilta-cel, or it would now be known as Carvykti.

This study overall was a positive study that lead to the approval of cilta-cel for this indication for patients with 1 to 3 prior lines of therapy with lenalidomide-refractory disease, which has really created a lot of enthusiasm, but also a lot of interest in seeing how this therapy performs as a second-line therapy for patients experiencing the first relapse. That's the object of this abstract.

For this abstract we emphasize the patients with functional high-risk, which are the patients who have progression within 18 months of the autologous transplant, or 18 months from the initial therapy for patients who did not receive transplant. Overall, there was about there was a 136 patients with this profile in the study, 68 in each arm of cilta-cel or control arm, and of which 40 and 39 respectively had functional high risk.

And when we look at the results, the cilta-cel arm produced more frequent responses, more frequent complete responses, and much more frequent MRD-negative responses than the control arm. And that translates to an improvement in progression for survival. That was notable for all patients with 1 prior line of therapy with a hazard ratio of 0.35, but was even more impressive for patients with functional high-risk disease with a hazard ratio of 0.27.

When you look at the safety profile, what we saw is very comparable with what we know about the cilta-cel toxicity and what we know for the entire study. The rate of grade 3 or higher diverse events and severe diverse events was comparable between the cilta-cel and the control arm in both the 1 line of therapy and 1 line of therapy and the function of high-risk populations. There will have a diverse event of special interest which are unique, of course, to CAR -T cell. CRS, which was present in 60% of the patients at some point, but only 1 case of grade 3 or higher CRS, which is compatible with the overall profile of cilta-cel. ICANS was uncommon, about 5% of the patients. We had a single case of cranial nerve palsy and a single case of parkinsonism that persists among the patients who receive cilta-cel.

This analysis emphasized the effect of cilta-cel on patients with 1 line of therapy, irrespective of being functional, high-risk or not, as long as they have received a prior potassium inhibitor and lenalidomide, and disease was resistant to lenalidomide. We think this data is going to be very helpful to healthcare professionals as they've encountered those patients in clinic, which is very common, to have a balanced discussion about risk and it and among the options, we're now having this renewed option of cilta-cel, a second-line therapy.

Source:

Costa L, Weisel K, van de Donk N, et al. Ciltacabtagene autoleucel vs standard of care in patients with functional high-risk multiple myeloma: CARTITUDE-4 subgroup analysis. Presented at the ASCO Annual Meeting. May 31–June 4, 2024; Chicago, IL. Abstract 7528