Bridging Therapy Response Predicts Outcomes With Cilta-cel in Multiple Myeloma

Key Clinical Summary:

• Design/Population: A subgroup analysis of the phase 3 CARTITUDE-4 trial evaluated the impact of bridging therapy response in 196 patients with relapsed, lenalidomide-refractory multiple myeloma receiving ciltacabtagene autoleucel after 1 to 3 prior lines, all treated with DPd or PVd bridging regimens prior to CAR-T infusion.
• Key Outcomes: Deeper responses to bridging therapy were associated with improved progression-free and overall survival after cilta-cel; at 30 months, >70% remained progression-free and >85% alive in responders. Patients who progressed during bridging had inferior outcomes and higher rates of non-relapse mortality, infections, and prolonged cytopenias. Improved bridging response also correlated with lower rates of severe adverse events, including absence of parkinsonism-type neurotoxicity.
• Clinical Relevance: Effective bridging therapy prior to CAR-T infusion is a key determinant of both efficacy and safety outcomes with ciltacabtagene autoleucel, supporting strategies to optimize disease control before CAR-T and improve long-term outcomes in relapsed multiple myeloma.

Binod Dhakal, MD, Medical College of Wisconsin, Milwaukee, Wisconsin, discusses post hoc analysis results from the phase 3 CARTITUDE-4 trial which evaluated the impact of bridging therapy response on outcomes after ciltacabtagene autoleucel among patients with relapsed, lenalidomide-refractory multiple myeloma. 

Results demonstrated that deeper responses to bridging therapy were associated with improved progression-free and overall survival, as well as better safety outcomes following CAR T-cell therapy.

Dr Dhakal presented these results at the 2026 Tandem Meetings in Orlando, Florida. 

Transcript:

Hello, I'm Binod Dhakal from the Medical College of Wisconsin. On behalf of my coauthors, I'm pleased to present "effectiveness of bridging therapy corresponds to improved outcomes after ciltacabtagene autoleucel: Phase 3 CARTITUDE-4 study of patients with relapsed, lenalidomide-refractory multiple myeloma."

In CARTITUDE-4, a single ciltacabtagene autoleucel (cilta-cel) infusion significantly improved progression-free and overall survival versus standard of care in patients with 1 to 3 prior lines of therapy. In this trial, a 25% or greater reduction in tumor burden after bridging correlated with longer progression-free survival after cilta-cel. Here, we further investigate the correlation between response to bridging therapy and efficacy and safety outcomes after cilta-cel infusion.

The CARTITUDE-4 study design was described previously. Of the 419 patients in the trial, 208 were randomized to cilta-cel, all of whom received bridging therapy which comprised of physician's choice of daratumumab plus pomalidomide and dexamethasone (DPd) or pomalidomide, bortezomib dexamethasone (PVd). The analysis population here comprised 176 patients who received cilta-cel cell as a study treatment plus 20 who progressed on bridging therapy and went on to receive cilta-cel as subsequent therapy. 

Median follow-up was about 34 months from randomized and about 30 months from cell to cell infusion. Most of the patients had received DPd as bridging therapy. Response to bridging prior to lymphodepletion in this population are shown here. About 1/5 had achieved very good partial response at better and about 1/3 achieved partial response to bridging therapy. We saw that the patients who had achieved partial response better to bridging therapy went on to experience superior progression-free survival and superior overall survival after cilta-cel infusion, particularly in comparison with 20 patients who had progressed during bridging. Notably, of the patients who achieved at least a partial response to bridging at 30 months after cilta-cel, over 70% were progression-free and over 85% were alive.

Of the 20 patients who received cilta-cel as subsequent therapy, 8 had first received salvage therapy after bridging and 9 would have been ineligible for CARTITUDE-4 as they had received 4 or more lines before cilta-cel. As shown earlier, progression-free survival in this group was worse than for those who received cilta-cel as a study treatment. After cilta-cel, as subsequent therapy, median progression-free survival was 7.4 months. Despite poorer overall outcome, 6 of these patients that is 30% remain progression-free at median 20.6 months after cilta-cel underscoring the significant benefit that cilta-cel can still provide patients with poor response to bridging.

With respect to safety, most adverse events of special interest occur at lower rates in patients with deeper response to bridging. Of note, non-relapse mortality, including fatal infections, occur more frequently in patients with poorer response to bridging with rates highest in those who progressed during bridging. In the subgroup, half of the deaths were due to adverse events with half of those being infections in the first 2 months after cilta-cel. Correspondingly, rates of prolonged grade 3/4 cytopenias were lowest in patients with a very good partial response or better before cilta-cel. No cases of immune effector cell-associated parkinsonism were observed in patients with partial response are better before cilta-cel. However, the rate of cranial palsy was lowest in the patients who progressed in bridging. That said, the pathophysiology of this neurological event is not well understood and appears to be unrelated to disease burden before CAR-T infusion.

In conclusion, in this study, deeper responses to breathing correlated with improved progression-free and overall survival after cilta-cel. Responses to bridging was also assumed to improve safety. Notably, no cases of immune effector cell-associated parkinsonism occurred in patients with at least a partial response to bridging, and patients with poorer response to bridging were more likely to have fatal adverse events, including infections as well as prolonged cytopenias after cilta-cel. Overall, we saw that effective bridging therapy correlated with better efficacy and safety after cilta-cel. Thank you.

Source:

Dhakal B, Iida S, Sidiqi MH, et al. Effectiveness of bridging therapy corresponds to improved outcomes after ciltacabtagene autoleucel: Phase 3 CARTITUDE-4 study of patients with relapsed, lenalidomide-refractory multiple myeloma. Presented at Tandem Meetings; Salt Lake City, Utah. February 4-7, 2026. Abstract 203.