Autologous Transplant vs CAR T-Cell Therapy in Patients With DLBCL in Complete Remission

CAR T-cell (CAR-T) therapy is widely established as a standard of care for relapsed or refractory (R/R) DLBCL. In many instances, due to the duration of time required to arrange T-cell collection and manufacture the CAR T-cell product, patients require “bridging therapy,” consisting of chemoimmunotherapy or radiation therapy, to temporarily treat their disease while waiting for CAR-T treatment. In some cases, this bridging treatment results in a complete remission (CR) prior to receiving CAR-T therapy. What should we do in these cases — move forward with CAR-T therapy or consider other approaches, such as high-dose chemotherapy and autologous stem cell transplant (auto-HCT)?

Shadman and colleagues aimed to address this question in a large retrospective study published in the Blood Cancer Journal. Using the CIBMTR registry, they identified 79 patients with R/R DLBCL who were in CR at the time of CAR-T therapy and 281 who were in CR at the time of auto-HCT. There were significant differences between the cohorts, with more early treatment failures, more prior lines of therapy, and worse performance status in those receiving CAR-T therapy. However, on multivariable regression analysis accounting for these differences, treatment with CAR-T was associated with worse progression-free survival (HR, 1.83; P = .0011) and a higher incidence of relapse (HR, 2.18; P < .0001) compared with auto-HCT. Overall survival was numerically superior in the auto-HCT cohort, but this was not statistically significant (HR, 1.44; 95% CI, 0.91–2.28).

So, if a patient is in CR after bridging therapy, should auto-HCT be chosen over CAR-T therapy? This manuscript provides an intriguing rationale for such an approach. Not only could auto-HCT provide better outcomes, but it may also allow for the CAR T-cell product to be reserved in the event of a subsequent relapse. However, there are some challenges in interpreting these findings. Not all patients are eligible for auto-HCT, and it is unclear whether all patients in the CAR-T cohort of this study would have met the criteria for auto-HCT. Also, many patients with R/R DLBCL are now receiving second-line CAR-T therapy, which was not included in this study. Finally, the majority of the CAR-T therapy administered in this study was tisagenlecleucel; recent data suggest that tisagenlecleucel may not be as efficacious in patients with DLBCL as axicabtagene ciloleucel or lisocabtagene maraleucel. This study’s findings warrant further evaluation, particularly in the second-line setting where CAR-T therapy or salvage chemotherapy with auto-HCT is the most commonly used. It is unlikely that a randomized clinical trial will be performed in this setting, and we will have to rely on well-designed retrospective studies such as this one to assess the relative merits of CAR-T therapy and auto-HCT for patients in CR after bridging therapy.