7043 Background: Combination trials of BTK inhibitors (BTKi) with CAR-T have suggested potential synergistic benefit by improving CAR-T immunophenotype and clinical outcomes but are limited by increased toxicity. We report immunophenotype, cytokine profile, and patient outcomes with the new non-covalent BTKi, pirtobrutinib (pirto) when given prior to LV20.19 CAR-T and compare the final CAR product to pts who did not receive pirtobrutinib prior to CAR. Methods: Pts received LV20.19 CAR-T as part of a phase 1/2 trial (NCT04186520). Only pts who received pirto £4 weeks prior to apheresis were included. To determine the impact of pirto on LV20.19 CAR-T, we calculated both polyfunctionality (PFA) and polyfunctional strength index (PSI) for each product using the Isoplexis. Descriptive statistics, t-tests and Kaplan-Meier method were used as appropriate. Results: 11 pts received pirto prior to LV20.19 CAR-T (Table). Median age was 65 (50-80) yrs and median prior lines of therapy were 4 (2-8). There were 4 MCL pts, 5 Richter’s (RT)/CLL, 1 MZL and 1 DLBCL. Median duration of pirto was 4 (1-20) mo. Pts were on pirto for a median of 12 (1-22) days prior to apheresis. All except 1 pts received target CAR-T dose. The day 28 ORR was 82% (CR=7, PR=2). After a median follow up of 13 mo, 3 pts died (PD, Covid, Guillain Barre). The median PFS and OS were both 30.8 mo while the 1-year PFS and OS rates were 9 and 15 mo respectively. 9 pts had CRS and 2 had ICANS, all grades 1-2, while 4 had IEC-HS. One pt had afib recurrence and 1 pt had CMV viremia within 30 days of CAR-T. Among the pts with immunophenotypic data (n=10), there were no differences in naïve or more differentiated T-cell percentages in apheresis and final CAR-T products when compared to pts who did not receive pirto before LV20.19 CAR-T (n=57). Although not statistically significant, both PFA (CD4=61.8 vs 59, CD8= 49.8 vs 46.9) and PSI (CD4= 1752 vs 1608, CD8=1299 vs 1079) were higher with pirto pre-treated pts, suggesting a potential trend towards improved CAR-T functionality. Conclusions: These data represent the largest experience of pirto prior to CAR-T apheresis and demonstrate that pirto can be safely used as a bridge to LV20.19 CAR-T without negatively impacting their immunophenotype and potentially improving functionality. These data support our planned phase 1 clinical trial to assess the safety of pirto as bridging and maintenance therapy with LV20.19 CAR-T (NCT05990465). [Table: see text]