6% (95% CI, 66.0%-84.3%). In those who achieved an sCR, the 12-month PFS rate was 84.5% (95% CI, 72.0%-91.8%) and was 68.0% (95% CI, 46.1%-82.5%) in patients who had a very good partial response.
“Patients with relapsed/refractory myeloma have a median overall survival of only 9.2 months in triple-refractory [disease] and only 5.6 months in penta-refractory. In this study, we know that the median PFS is at least a full year and we still haven’t even reached a median PFS after a median duration of follow-up of 12.4 months,” Madduri commented.
Additionally, cytokine release syndrome (CRS), a common CAR T-cell therapy–related AE, was reported in 94
At 1 year, the overall survival rate was 88.5% (95% CI, 80.2%-93.5%). The median overall survival was also not yet reached.
The most common grade 3/4 adverse events (AEs) were hematologic and observed in 99.0% of all patients, consisting of neutropenia in 94.8%, anemia in 68.0%, leukopenia in 60.8%, and thrombocytopenia in 59.8%. The median time to recovery of these grade 3/4 cytopenias was 2 weeks for neutropenia and 4 weeks for thrombocytopenia. The rate of any-grade infections was 57.7%, and the most common grade 3/4 infections were pneumonia (8.2%) and sepsis (4.1%).
Grade 3/4 non-hematologic toxicities were not common in the study, including hypophosphatemia at 7.2%, fatigue at 5.2%, aspartate aminotransferase increase at 5.2%, and hyponatremia at 4.1%.
“One distinguishing aspect of this study is the median time to onset of CRS, which is 7 days, with 89% of these patients having CRS at day 4 or later and 74% of these patients having CRS at day 6 or later, opening the possibility of outpatient administration. This may be explained by the fact that the maximum peripheral expansion of cilta-cel occurred generally around a median of 13 days,” Madduri said.
Tocilizumab and corticosteroid support were required in 69.1% and 21.6% of patients, respectively. CRS resolved in 98.9% of all patients within 14 days of onset.
Neurotoxicity, another known complication of CAR T-cell therapies, was reported in 20.6% of patients at any grade and of grade 3 or higher in 10.3%. Specifically, immune effector cell–associated neurotoxicity syndrome (ICANS) cases were reported in 16.5% at any grade and of grade 3 or higher in 2.1%. All ICANS occurred within a median of 8 days (range, 3-12) and resolved within a median of 4 days (range, 1-12).
Other neurotoxicities, which were reported in 12 patients (12.4%), occurred after resolution of CRS or ICANS and included 5 patients with movement and/or neurocognitive changes and 7 with nerve palsy or peripheral motor neuropathy; 6 of these resolved. In the other 6 patients, 1 patient died from complications of the AE, 4 died of other causes, and 1 has ongoing neurotoxicity. The median time to onset for these toxicities was 27 days (range, 11-108) with recovery in a median of 75 days (range, 2-160).
“We saw no clear etiology in the other neurotoxicities, but we saw that maybe there could be some mild associations with high tumor burden, prior CRS, ICANS, or even the higher expansion and persistence of these CAR T cells.
So we did implement some mitigation strategies in our subsequent CARTITUDE development program allowing patients to have more chemotherapy, having more aggressive steroids for ICANS, like early intervention and extensive monitoring,” Madduri said in the question-and-answer portion of the session following her presentation
A total of 14 patients died during the study within 45 to 694 days of infusion. Five patient deaths were due to progressive disease, 3 were due to AEs that were not related to treatment, and 6 were due to AEs considered to be related to treatment with cilta-cel. These AEs included sepsis and/or septic shock in 2 patients, and CRS or hemophagocytic lymphohistiocytosis, lung abscess, respiratory failure, and neurotoxicity in 1 patient each.