LAUSR

Background & Aim Background: Tisagenlecleucel (CTL019) is approved for treatment of relapsed/refractory (r/r) aggressive B-cell lymphomas after second line therapy. Prior to CTL019 release for commercial use in the United States, the final manufactured, patient-specific product must meet specific Lot Release Specifications. CAR T cell products that do not meet predetermined release specifications are considered “out of specification” (OOS). Aim To describe reasons commercial CTL019 products were OOS and examine clinical outcomes with use of OOS CTL019. Methods, Results & Conclusion Methods We are participating in a prospective, managed access protocol to allow administration of OOS CTL019 to patients (pts) with r/r aggressive B-cell lymphomas. Pts were provided product via this managed access program. Consent was obtained from all pts. Clinical response was assessed at 3 months post CTL019 infusion. Results 18 pts were enrolled at our institution. Eleven pts had r/r DLBCL, 5 pts had r/r HGBCL, and 2 pts had r/r tFL. Median age was 65.3 years (range: 41-75 years); 7 pts (39%) were female. Fourteen pts (78%) had advanced stage lymphoma. Median ECOG performance status was 0 (range: 0-2). Median prior therapies was 3 (range: 2-5). Median absolute lymphocyte counts and CD3 counts were 850 / uL (range: 200-1300) and 601 / uL (range: 228-1343), respectively. Median CTL019 dose was 1.4 × 108 CAR-positive viable T cells (range: 0.5 × 108-2.5 × 108). Median product viability was 78.65% (range: 70.8-87.4%). Fifteen of 18 pts (83%) were enrolled due to low viability products (viability 1000 fg/transduced cell (n=1). Of 18 pts enrolled, 15 pts have at least 3 months of follow-up. Median follow-up is 3.5 months. Five pts had CRS grades 1-2 by ASTCT criteria and no pts had neurotoxicity. Of the 5 pts with CRS, one received a low dose of CTL019 (grade 2 CRS), one had higher levels of IFN gamma (grade 1 CRS), and three had low viability (all grade 1 CRS). For all pts infused with OOS products, the 3-month overall response rate (ORR) is 60%, including 7/15 (47%) CR and 2/15 (13%) PR. Conclusions Commercially produced CTL019 products were OOS primarily due to low viability. Three-month overall response rates appear similar to published tisagenlecleucel outcomes for aggressive B-cell non-Hodgkin lymphomas.