Factors Influencing Prescribing Patterns and Patient Management Among US Centers Offering Commercial Axicabtagene Ciloleucel and Tisagenlecleucel for B-NHL

Abstract

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are both anti-CD19 chimeric antigen receptor (CAR) T-cell therapies indicated for the management (mgmt) of relapsed/refractory large B-cell non-Hodgkin lymphoma (B-NHL). Though two registrational phase 2 trials yielded promising results, comparison studies are lacking and long term data are not yet available. Given the approval of axi-cel in 10/2017 and tisa-cel in 5/2018, we conducted a survey in 7/2018 to better understand early prescribing patterns and mgmt strategies with these two commercial products in B-NHL. Surveys were issued to 26 US centers certified to prescribe both drugs, with 19 (73%) surveys returned. Of respondents, 26% took part in axi-cel trials, 26% in tisa-cel trials, 26% did not take part in either, and 21% took part in trials with both drugs. Tisa-cel was most frequently delivered in a hybrid setting (outpatient (outpt) chemotherapy and inpatient (inpt) CAR T infusion) in 42% of sites, 37% performed exclusively inpt treatment (tx), 11% outpt tx, and 11% used multiple tx strategies. Axi-cel was administered exclusively inpt in 47% of sites, 42% used a hybrid approach, and 11% used multiple tx strategies; however, no site employed entirely outpt axi-cel tx. There was significant variability in supportive care measures across sites. In grading toxicities, 32% of centers used Lee criteria, 32% CAR-T associated Toxicity (CARTOX) criteria, 21% center specific policies, and 16% company guidance. Similarly, toxicity mgmt varied greatly, where 42% of sites used center specific policies, 21% Lee criteria, 21% company guidance, and 16% CARTOX. In 68% of respondents, baseline patient (pt) factors impacted prescribing patterns. Tisa-cel was more likely to be considered in pts with advanced age/comorbidities or a history of central nervous system B-NHL/other neurologic conditions. In 84% of sites, product logistics influenced prescribing practice. The most frequently cited reasons were shorter production time favoring use of axi-cel followed by later onset of cytokine release syndrome favoring use of tisa-cel. Of respondents, the single strongest reason influencing tx decisions was drug toxicity profile (32%). The results of this survey highlight the significant heterogeneity in practice patterns that exist among sites offering both products in B-NHL. While numerous factors may impact prescribing patterns, toxicity profile and production time appear to heavily influence this decision. Given the limited available data and the relatively small number of pts treated with commercial drug at each site, open discussions about institutional experiences will be important in understanding the pros and cons of various approaches and products. Future efforts should focus on formulating consensus guidelines to standardize prescribing patterns and supportive care measures, with the goal of optimizing outcomes.