A Multicenter Retrospective Analysis of Outcomes and Toxicities with Commercial Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed/Refractory Aggressive B-Cell Lymphomas

Abstract

<h3>Introduction</h3> CD19 directed CAR T cells have potent activity in relapsed/refractory (R/R) aggressive B-cell lymphomas (B-NHL) leading to the FDA approval of axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel). Initial reports on commercial use of axi-cel suggest many patients (pts) would not have met eligibility criteria for ZUMA-1, yet outcomes and toxicities appeared similar. Limited data on the "real world" use of tisa-cel is available. We performed a multicenter retrospective study to evaluate efficacy, safety, and patterns of use in 8 US centers that had the option of prescribing either commercial product for R/R B-NHL. <h3>Results</h3> As of 7/31/2019, 242 pts underwent apheresis for axi-cel or tisa-cel. Of these, 163 (67%) underwent apheresis for axi-cel, and 79 (33%) for tisa-cel. 14 (9%) axi-cel and 3 (4%) tisa-cel pts died prior to CAR T-cell infusion from lymphoma progression, and 1 (1%) tisa-cel pt was not infused for other reasons. Detailed baseline pt characteristics were available for 180/242 pts (Figure 1). Median age at apheresis was 58 years (range: 18-85) for axi-cel and 67 years (range: 36-88) for tisa-cel. ECOG PS was 0-1 in 86% of axi-cel and 94% of tisa-cel pts. The median number of prior therapies was 3 (range: 2-11) for axi-cel and 4 (range: 2-9) for tisa-cel pts. Bridging therapy was given in 61% of axi-cel and 72% of tisa-cel pts. Median time from apheresis to CAR T-cell infusion was 28 days for axi-cel and 44 days for tisa-cel. CAR T-cell infusion was inpatient in 100% of axi-cel and 39% of tisa-cel pts. Safety was evaluable in 213 pts. CRS was graded according to institutional practices (CARTOX (38%), Penn scale (31%), ASTCT (19%), and Lee scale (11%)). NEs were graded per CARTOX (80%), ASTCT (19%), or CTCAE V4.03 (1%). Grade ≥3 CRS and NEs occurred in 13% and 41% of axi-cel pts and 1% and 3% of tisa-cel pts. The median onset of CRS and NEs was 2 and 6 days in axi-cel, and 3 and 5 days in tisa-cel treated pts, respectively. Tocilizumab was administered in 62% of axi-cel pts with 57% receiving steroids. In tisa-cel pts, tocilizumab was administered in 13% of cases, with 7% receiving steroids. Response assessment was performed for infused pts at day 30 and/or day 90, or in those with clinical progression. Of 120 axi-cel pts evaluable at day 30, the ORR was 72% with 43% achieving a CR. Of the 32 tisa-cel pts evaluable at day 30, the ORR was 59% with 44% achieving a CR. At day 90, the ORR for axi-cel was 52% with 39% achieving a CR, while for tisa-cel the ORR was 48% with 39% achieving a CR. <h3>Conclusions</h3> Efficacy outcomes in the commercial setting appear similar to responses seen in the pivotal clinical trials. Though different toxicity grading scales were employed, tisa-cel appears to be associated with less CRS and NEs. Updated analyses of usage patterns and outcomes with uniform ASTCT toxicity grading will be presented at the meeting.