Your AI-Trained Oncology Knowledge Connection!
CARTITUDE-4 data show heterogeneous outcomes with cilta-cel after progression on bridging therapy in relapsed/refractory multiple myeloma.
Improved responses to bridging therapy correlated to improved efficacy and safety outcomes ciltacabtagene autoleucel (cilta-cel; Carvykti) in patients with relapsed or refractory multiple myeloma, according to an analysis of the phase 3 CARTITUDE-4 trial (NCT04181827).1
Findings presented at the
Based on best response to bridging therapy, the 30-month progression-free survival (PFS) rates were 75.9% for VGPR, 72.9% for PR, 56.5% for MR/SD, and 30.0% for PD. The respective 30-month overall survival rates in these groups were 85.1%, 91.4%, 74.8%, and 40.0%.
Among the 20 patients who received cilta-cel as subsequent therapy after PD during bridging therapy, 8 also received salvage therapy prior to cilta-cel, leading to a median of 3 prior lines of therapy (range, 2-5) prior to cilta-cel administration; 9 total patients received cilta-cel after at least 4 prior lines of therapy, which would have made them ineligible for enrollment on CARTITUDE-4. In patients with progressive disease during bridging, the median PFS from cilta-cel infusion was 7.4 months. By the data cutoff, 12 deaths had occurred in this subgroup. Notably, 6 deaths were attributed to adverse effects (AEs), with infections accounting for half of these deaths within the first 2 months following infusion.
Despite these overall trends, a subset of patients with PD during bridging therapy derived durable benefit with cilta-cel. Thirty remained progression-free at a median of 28.6 months (range, 25.4-35.7) after infusion.
“Effective bridging therapy correlated with better efficacy and safety outcomes after cilta-cel, emphasizing the need to optimize bridging therapy,” lead study author Binod Dhakal, MD, and colleagues wrote in a poster presentation of the data. “Patients with poorer responses to bridging therapy were more likely to have fatal infections, prolonged thrombocytopenia and neutropenia, and higher rates of non-relapse mortality following cilta-cel infusion.”
Dhakal is an associate professor of medicine at the Medical College of Wisconsin in Milwaukee.
CARTITUDE-4 evaluated cilta-cel vs standard-of-care therapy in patients with relapsed/refractory multiple myeloma; prior data from the study supported
Eligible patients were adults 18 years of age or older with multiple myeloma that was refractory to lenalidomide and who had an ECOG performance status of 0 or 1.1Key exclusion criteria included prior CAR T-cell therapy or prior BCMA-targeted treatment. Following screening, patients were randomly asssigned 1:1 to receive either cilta-cel or standard-of-care therapy consisting of pomalidomide (Pomalyst) plus bortezomib (Velcade) and dexamethasone (PVd) or daratumumab (Darzalex) plus pomalidomide and dexamethasone (DPd). Randomization was stratified by choice of PVd vs DPd, International Staging System stage, and number of prior lines of therapy.
Patients assigned to the cilta-cel arm were permitted to receive bridging therapy with PVd or DPd for up to two cycles at investigator’s discretion prior to CAR T-cell infusion. Leukapheresis was followed by lymphodepleting chemotherapy, after which patients in the experimental arm received a single infusion of cilta-cel at a target dose of 0.75 × 106 CAR-positive T cells/kg.
The analysis population included patients who received cilta-cel either as protocol-defined study treatment or as subsequent therapy.
Overall, 419 patients were randomized, including 208 assigned to cilta-cel and 211 to standard-of-care therapy. Among patients randomized to the cilta-cel arm, 196 ultimately received both bridging therapy and CAR T-cell infusion. Median follow-up was 33.7 months from randomization and 30.4 months from infusion
Most patients in the cilta-cel arm received DPd as bridging therapy (87.8%). The median number of bridging cycles was 2 for DPd and 3 for PVd among patients receiving cilta-cel as study treatment. Among those who received cilta-cel as subsequent therapy, the median bridging duration was 2 (range, 1-6) for DPd and 2 (range, 1-3) for PVd.
Cytokine release syndrome occurred in 66.7% of patients who achieved VGPR or better to bridging therapy, 75.7% of those with PR on bridging therapy, 83.6% with MR/SD, and 85.0% with PD. Immune effector cell–associated neurotoxicity syndrome (ICANS) was reported in 4.8% in the VGPR or better group, 4.3% in the PR group, 4.9% in the MR/SD group, and 35.0% in the PD group. Rates of cranial nerve palsy were 11.9%, 7.1%, 8.2%, and 5.0%, respectively.
Rates of AEs of special interest also differed by bridging response, particularly for IEC-associated Parkinsonism, infections, non-relapse mortality, and prolonged cytopenias. IEC-associated Parkinsonism was not observed in patients who achieved VGPR or better or PR; it was reported in 1.6% of patients with MR/SD and 5.0% of those with PD. Grade 3/4 infections occurred in 40.5% of patients with VGPR or better, 35.7% in those with PR, 41.0% for those with MR/SD, and 30.0% in patients with PD; fatal infections were reported in 2.4%, 4.3%, 13.1%, and 15.0% of patients, respectively.
Non-relapse mortality was highest among patients with PD during bridging (30.0%) vs 7.1% with VGPR or better, 8.6% with PR, and 18.0% with MR/SD. For prolonged grade 3/4 cytopenias, thrombocytopenia occurred in 9.5% in the VGPR group, 11.4% in the PR group, 11.5% in the MR/SD group, and 50.0% in the PD group; neutropenia rates were 2.4%, 15.7%, 9.8%, and 10.0%, respectively; and anemia occurred at respective rates of 0% 1.4%, 1.6%, and 15.0%.
