CAR T Therapy Referral for Diffuse Large B Cell Lymphoma (DLBCL) By U.S. Community Hematology/Oncology (cH/O) Practices: Perceptions and Patterns
Authors: Porter David L , Klink Andrew J , Balanean Alexandrina , McAllister Lindsay , Feinberg Bruce A. 
Published: November 2021

Abstract
Introduction
Chimeric antigen receptor T-cell (CAR T) therapy has resulted in a treatment paradigm shift for certain hematologic malignancies, with United States Food and Drug Administration approval of several products for patients with relapsed/refractory (RR) aggressive B cell lymphomas (BCL). Although most BCL patients are initially treated by cH/O physicians, current delivery of CAR T is limited to major academic centers. Consequently, there is a dearth of reporting on the complex aspects of cH/O involvement before and after CAR T therapy administration, which complicates determination of the magnitude of potential benefits. To appropriately incorporate this therapeutic option, and optimize patient care, communication and cooperation between cH/O and the CAR T center is critical; at a minimum, the referring cH/O's access to all aspects of the CAR T therapy continuum is paramount. To that end, this study surveyed cH/O physicians to determine: 1) whether adequate data were recorded and available to the cH/O; 2) timing of referral, leukapheresis, and CAR T infusion; 3) treatment prior to CAR T referral, and 4) physician perceptions on patient eligibility, barriers to access, and noncompliance.
Methods
This retrospective, observational, multicenter chart review assessed adult patients with RR DLBCL who received CAR T therapy in 2019. Patients with ≥6 months of post-CAR T therapy administration follow-up were identified by cH/O physicians participating in the Cardinal Health Oncology Provider Extended Network (OPEN). cH/O physicians provided their perceptions and experience with CAR T therapy via survey and abstracted patient data using electronic case report forms. Patient demographic/clinical/treatment characteristics and physician perceptions were summarized descriptively.
Results
Surveyed Perceptions: Top barriers to CAR T referral: patient choice (39%), location of CAR T center (31%), and preference for other therapy (31%); 39% reported no specific barriers. Rapid disease progression (69%) was the main reason patients would not undergo CAR T therapy after referral, followed by patient ineligibility (62%), patient choice (62%), and insurance coverage/patient cost (46%). Chart Abstraction: Data on 65 RR DLBCL patients were collected from 13 cH/O practices in all 4 U.S. regions (Table). Median duration of follow-up from CAR T therapy referral was 15 months. Median age at RR DLBCL diagnosis was 60 years, and most patients were male (63%) and White (79%). Most patients (92%) received anti-CD20 monoclonal antibody (mAb) + CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) as 1L therapy. At referral, 80% of patients (48/60) had lactate dehydrogenase levels above the upper limit of normal. Prior to CAR T infusion, all patients were reported to receive lymphodepletion treatment with fludarabine + cyclophosphamide. Median intervals among patients with and without disease progression, respectively, were: 9 weeks (8 vs 10) from CAR T referral to CAR T infusion, which comprised 5 weeks (4 vs 6) from CAR T referral to leukapheresis and 4 weeks (both groups) from leukapheresis to CAR T infusion.
Conclusions
The cH/O physicians' perceived barriers to CAR T therapy for their patients appear to conflict with the patient data; 69% thought that rapid disease progression precluded CAR T therapy but the reported 9-week interval from referral to CAR T infusion suggests reasonably timely intervention. This highlights the critical need for early referral with a commitment to prompt patient evaluation by the treatment center. The cH/O physician is vital for CAR T referrals and treatment decisions, and the recent increasing access to patients via telemedicine may help better integrate the cH/O, the patient, and the treatment center to promote access of patients to CAR T cell therapies, particularly when limited other options are available.
Figure 1 Figure 1.

Disclosures
Porter: DeCart: Membership on an entity's Board of Directors or advisory committees; American Society for Transplantation and Cellular Therapy: Honoraria; Incyte: Membership on an entity's Board of Directors or advisory committees; ASH: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Genentech: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees; National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Tmunity: Patents & Royalties; Wiley and Sons Publishing: Honoraria. Klink: Cardinal Health: Current Employment, Current holder of stock options in a privately-held company. Balanean: Cardinal Health: Current Employment; Georgia State University: Other: former student and employee. McAllister: Cardinal Health: Current Employment. Feinberg: Cardinal Health: Current Employment.