Impact of bridging chemotherapy on clinical outcome of CD19 CAR T therapy in adult ALL.

Abstract

2520 Background: Autologous chimeric antigen receptor (CAR) T cell therapy has shown to be effective in CD19+ relapsed or refractory (R/R) B-ALL but requires a 2-4 week period of cell processing and manufacture. During this “bridging period,” patients are vulnerable to disease progression and complications. We sought to characterize bridging strategies in our published study of CD19 CAR T cell therapy in adults with R/R ALL (Park et al., NEJM, 2018). Methods: We performed a retrospective review of adult patients with R/R ALL treated with 19-28z CAR T therapy at MSKCC. Bridging therapy was defined as any therapy given from trial enrollment to cell infusion and classified as either high intensity (remission-inducing or myelosuppressive regimens, eg hyper-CVAD or high-dose cytarabine based regimens) or low intensity (maintenance and/or less myelosuppressive regimens, eg POMP, Blinatumomab, TKI). Results: Of 53 patients who received CAR T cell infusion, 19 were bridged with a high intensity regimen and 34 with a low intensity regimen. There was no difference in number of prior therapies, pre-bridging chemotherapy disease burden, and prior transplant status between groups. High intensity therapy was associated with a higher rate of Gr3-4 infectious complications during the bridging period (78% vs 32%, p < 0.002 by Fisher’s Exact) but not with response to bridging or CAR T cell therapy, relapse free survival, post-CAR Gr3-4 cytokine release syndrome (CRS) or neurotoxicity (NT). Patients in both groups who converted from morphologic to molecular disease during bridging (n=9) had a decreased rate of eventual severe CRS (0% vs 41%, p=0.01) or NT (0% vs 55%, p <0.01) compared to patients with persistent morphologic disease. In all patients enrolled on trial (n=83), use of high compared to low intensity bridging was not associated with higher rates of successful CAR T cell infusion (63% vs 79%, p>0.05) or a combined endpoint of CAR T cell infusion or alternative therapy including transplant (80% vs 86%, p> 0.05). Conclusions: High intensity bridging therapy is associated with a high risk of infectious complications without a clear benefit in outcome in R/R ALL receiving CD19 CAR T cells. Selection of bridging regimen therefore requires consideration of previous treatments and patient status to maximize the efficacy and safety. Clinical trial information: NCT01044069.