The CARTITUDE-4 trial shows that how well patients respond to bridging therapy — treatment given while waiting for CAR T-cell manufacturing — strongly affects how well cilta-cel (Carvykti) works in relapsed or refractory multiple myeloma. Patients whose disease improved or stayed stable during this waiting period had much better survival and fewer serious side effects than those whose disease worsened.
At 30 months, progression-free survival (PFS) was about 76% for patients with very good partial response (VGPR) or better, 73% for those with partial response, and 57% for those with stable disease. In contrast, it was only 30% for patients whose disease progressed. Overall survival (OS) was 85% to 91% in responders, but just 40% in those with progressive disease. Patients who progressed during bridging had a median PFS of only 7.4 months.
Patients with poor bridging response also experienced more severe side effects after cilta-cel infusion. Neurotoxicity (ICANS) occurred in 35% of patients with progressive disease, compared with about 5% in responders. Fatal infections were more common (15% vs. 2.4%), and serious blood-related problems such as prolonged low platelets (50%) and anemia (15%) were higher. Non-relapse mortality reached 30% in patients with progressive disease, compared with 7% in the best responders. The study included adults with lenalidomide-refractory multiple myeloma and compared cilta-cel with standard treatments. The findings suggest that preventing disease progression during bridging therapy is critical to achieving the best outcomes with CAR T-cell treatment.