Abstract PO-55: Single-center experience of chimeric antigen receptor T-cell (CAR-T) immunotherapy in relapsed/refractory large B-cell lymphoma identifies association of acute toxicities with inferior disease outcomes
Authors: Basher Fahmin , Coughlin Caroline A. , Kwon Deukwoo , Lekakis Lazaros , Schatz Jonathan 
Published: December 2020

Chimeric antigen receptor T (CAR-T) cells are an emerging approach for the treatment of hematologic and solid tumor malignancies. Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel were the first FDA-approved CAR-T therapies targeting CD19 for patients with relapsed/refractory (r/r) large B-cell lymphoma. Pivotal studies showed complete response (CR) rates of 58% and 40%, respectively, and we sought to investigate if the data are similar to our single-center results. We carried out a retrospective analysis of patients diagnosed with r/r diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, or mantle cell lymphoma who were treated with axi-cel or tisagenlecleucel at Sylvester Comprehensive Cancer Center in Miami, FL between January 2016 and October 2019. Primary objectives were to identify clinical characteristics associated with improved overall and progression-free survival (OS and PFS). Secondary analyses included incidence of post-CAR-T toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Our analysis included 44 patients: 32 received FDA-approved commercial product and 12 received axi-cel through clinical trials. Median age at time of CAR-T therapy was 62 years, and 70% of patients were male. Median number of prior treatments was 4, and 14 patients had undergone prior hematopoietic stem cell transplantation (12 autologous, 2 allogeneic). By day-30 post-treatment PET scan, 25 patients (57%) achieved CR or partial response (PR), while 16 (36%) had progressive (PD) or stable disease (SD). The remaining 3 patients decompensated rapidly post-infusion. Overall, patients with a CR or PR at 30 days had significantly improved OS and PFS compared to patients with PD or SD (OS p = 0.009, PFS p &lt; 0.001). Univariate analyses showed patients requiring aggressive supportive measures in the post-infusion period had decreased OS compared to those who did not: requirement for ICU care (p = 0.018), vasopressor use (p = 0.01), and steroid treatment (p = 0.018) were all associated with inferior survival. There was no survival difference in DLBCL patients classified as double expressor or double hit; however, patients with germinal center B-cell (GCB) DLBCL trended strongly towards improved OS (p = 0.073) compared to non-GCB patients. CRS affected 35 patients (80%), while 24 patients (55%) experienced ICANS. Incidence of toxicities did not vary significantly in patients who received CAR-T commercially or in clinical trials. Patients who did not experience CRS had improved OS (p=0.061), and of patients who had CRS or ICANS, SD/PD patients had significantly worse PFS (p= &lt;0.001, p= 0.024). This single-center retrospective analysis of patients receiving CAR-T therapy for r/r large B-cell lymphoma showed that incidence and management of toxicities and factors such as tumor subtype associate with treatment response. Further investigations into these factors may provide more insight into optimal management of patients undergoing CAR-T therapy.

Citation Format: Fahmin Basher, Caroline A. Coughlin, Deukwoo Kwon, Lazaros Lekakis, Jonathan Schatz. Single-center experience of chimeric antigen receptor T-cell (CAR-T) immunotherapy in relapsed/refractory large B-cell lymphoma identifies association of acute toxicities with inferior disease outcomes [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-55.