Ciltacabtagene autoleucel benefit for lenalidomide-refractory FHR multiple myeloma
Dr Luciano Costa - University Of Alabama At Birmingham, Birmingham, USA
Here at ASCO 2024 we’re presenting on behalf of the CARTITUDE-4 investigators the subgroup analysis of that trial for patients with one prior line of therapy. CARTITUDE-4 was a trial that enrolled patients who had myeloma that was refractory to lenalidomide and had been previously exposed to a proteasome inhibitor. It randomised those patients to either a standard of care regimen, which was DPd or PVd at investigator’s choice, or that same regimen used as a bridging therapy leading into an infusion of cilta-cel after proper lymphodepletion therapy. Overall the study was a highly positive study and supported the approval in the US and all jurisdictions of cilta-cel as a therapy for patients with 1-3 prior lines of therapy.
In this abstract we’re really zooming in on the patients with one prior line of therapy, including the patients who have what we call functional high-risk disease which is myeloma that progresses within 18 months of the initial therapy or within 18 months of the autologous transplant. In this analysis we saw that the cilta-cel outperformed the standard of care in terms of frequency of responses, depth of responses, particularly MRD negative responses, and that translates into a substantial improvement in progression free survival. That was with a hazard ratio of 0.35 for patients with one prior line of therapy but when you look at patients with functional high risk that impact was even greater with a hazard ratio of 0.27.
When you look at the safety profile, the frequency of grade 3 or higher adverse events and the frequency of severe adverse events was very similar between the cilta-cel and the standard of care arms. The safety profile of cilta-cel that was seen was very in line with what we know for the overall study, with most patients having CRS but very infrequently grade 3 or higher CRS, very infrequently ICANS and very infrequently having other delayed neurotoxicity.
What could be the impact of this research?
This data is very important as we embrace with the reality that we now have cilta-cel approved for patients with one prior line of therapy as long as they are exposed to a PI and lenalidomide refractory. So we are all reassessing our practices and seeing how to best utilise that agent.
Of course, those patients with functional high risk are perceived as having a great unmet need. This study confirms that for those patients there is a substantial, robust benefit of clita-cel over standard of care. But it also showed that the benefit is not limited to those functional high risk patients; the same, or very similar, magnitude of benefit is seen throughout all the patients with one prior line of therapy. That really adds some important efficacy and safety data that myeloma physicians like myself are going to use when they discuss with the patients the potential impact of cilta-cel as compared to other options that they have available.
