ASH Highlights and Commentary: Additional Topics of Interest

Abstract

884 Outcomes and Treatment Patterns in Patients With Aggressive B-Cell Lymphoma After Failure of Anti-CD19 CAR T-Cell Therapy Joanna C. Zurko, MD, Narendranath Epperla, MD, MS, Imran Nizamuddin, MD, Pallawi Torka, MD, Kevin A. David, MD, Thomas A. Ollila, MD, Brian T. Hess, MD, Jonathon B. Cohen, MD, MS, Robert Ferdman, MD, Jieqi Liu, MD, Sayan Mullick Chowdhury, DO, PhD, Kaitlyn O’Shea, PhD, Jason Romancik, MD, Rahul Bhansali, MD, Elyse Harris, MD, Mckenzie Sorrell, D.O., Rebecca Masel, Lindsey Fitzgerald, MD, Carlos Galvez, MD, Shuo Ma, MD, Jane N. Winter, MD, Barbara Pro, MD, Leo I. Gordon, MD, Alexey V. Danilov, MD, PhD, Deborah M. Stephens, Nirav N. Shah, MD, Geoffrey Shouse, PhD, Vaishalee P. Kenkre, MD, Stefan K. Barta, MD, MRCP, MS and Reem Karmali, MD, MSc Visit https://doi.org/10.1182/blood-2021-147433 for a complete list of contributor affiliations and full graphics. Background: Anti-CD19 chimeric antigen receptor T-cell therapy (CART) is a highly active therapy for relapsed/refractory (R/R) aggressive B-cell lymphoma. Nonetheless, most patients (pts) ultimately develop progressive disease (PD). There is little guidance on the optimal treatment approach(es) for these pts. We performed a multicenter retrospective analysis with a primary objective to assess treatment patterns and outcomes in pts with R/R aggressive B-cell lymphoma who develop PD after anti-CD19 CARTs. Methods: Pts with aggressive B-cell lymphoma treated with anti-CD19 CART between 2015 and 2020 across 12 US academic medical centers were included. Demographic and clinical characteristics were collected along with CART toxicities and response. Regimens administered as salvage post CART were assessed. Univariate analyses (UVA) were performed to determine impact of demographic and clinical variables on survival outcomes. All p-values were two-tailed. Survival curves were calculated using the KaplanMeier method. Results: A total of 400 pts received anti-CD19 CARTs and were included for analysis. For the entire cohort: median PFS and OS from time of CART infusion were 11 months [mo] and 27 mo respectively. On log-rank testing, pts who received ≥3 lines of pre-CART therapy and those with refractory disease pre-CART had significantly worse PFS (p=0.004 & 0.001) and OS (both p<0.001). With median follow-up 22.4 mo, 190 pts (48%) had PD after CART; demographic and clinical variables of pts with and without PD are detailed in Table 1. Biopsy to confirm PD and assess CD19 status was done in 69 pts (36%) with CD19 negative relapse seen in 11 (16%). Of pts with PD, median PFS and OS from time of PD was 83 days (in pts who received salvage) and 174 days (for all PD pts) respectively. Pts with PD were more likely to have elevated LDH (p=0.001) and extranodal disease (p=0.003) at apheresis. For pts with PD after CART: 125 (65.5%) received further therapies. Pts were more likely to receive salvage therapies if their best response to CART was CR (p=0.026) or PR (p=0.015). Response rates of select firstand second-line therapies and PFS of first line therapies received after CART failure are detailed in figure 1. ORR and CRs were highest for polatuzumab, bendamustine, & rituximab (pola-BR; 73% & 40%), followed by BTK inhibitors (BTKi; 50% & 38%), and bispecific antibodies (bsAb) (50% & 25%). Five of 7 pts who received a BTKi had non-germinal center (GC) cell of origin (COO; 1 unknown COO). On log-rank testing, pts with elevated LDH (p=0.003) at time of apheresis and those with intermediate/high IPI (p=0.013) had inferior PFS J Adv Pract Oncol 2022;13(suppl 2):25–32 https://doi.org/10.6004/jadpro.2022.13.2.12 Th is ar tic le is dis tri bu te d u nd er th e t er m s o f t he Cr ea tiv e C om m on s A ttr ibu tio n N on -C om m er cia l N on -D er iva tiv e L ice ns e, wh ich pe rm its un re str ict ed no nco m m er cia l a nd no nde riv at ive us e, dis tri bu tio n, an d r ep ro du cti on in an y m ed ium , p rov ide d t he or igi na l w or k i s p ro pe rly ci te d.