AUSTRALIAN PATIENTS WITH RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA FREQUENTLY FAIL ELIGIBILITY CRITERIA FOR LANDMARK AND REGISTRATION CLINICAL TRIALS.

Abstract

Introduction: Patients (pts) with relapsed Diffuse Large B Cell Lymphoma (rDLBCL) following or due to ineligibility for salvage Chimeric Antigen Receptor T cell therapy (CAR-T) or autologous transplant have a 2-year survival of 20% (Vardhana, 2017). More than 7 new therapies have been approved for rDLBCL since 2010 based on registrational trials, for example, tafasitamab-lenalidomide (Salles, 2020), polatuzumab plus bendamustine and rituximab (Sehn, 2020), selinexor (Kalakonda, 2020), loncastuximab (Caimi, 2021) and 3 CAR-T products. Enrolled cohorts in these trials are however highly selective, making applicability to real-world (RW) populations unclear. Small post-marketing analyses of these individual regimens show a low rate of trial eligibility in RW cohorts (Shaw, 2023), but a comparison of all 7 registered therapies has not been undertaken. Method(s): This multicentre study applied eligibility criteria from 7 pivotal trials (SADAL, polatuzumab-BR, L-MIND, LOTIS-2, ZUMA-7, TRANSCEND, JULIET) to adult rDLBCL treated between 2010 and 2022 from 5 Australian centres (IRB approval: LNR/17/Austin/186). Pts were included if refractory to prior treatment (did not achieve complete remission) or relapsed following completion of treatment. Eligibility for pts at relapse was assessed based on inclusion and exclusion criteria from each trial. Descriptive statistics were used to quantify the proportion of eligible episodes. Result(s): 180 pts were identified with 320 relapse/refractory episodes. Median age was 65, 58% were male, 90 (51%) had a high-risk R-IPI at baseline. Median number of prior therapies was 1 (range 1-8). Median overall survival (OS) of the whole cohort was 16.4 m (0.03-123) from first relapse, median progression free survival (PFS) across all relapse episodes was 7.2 m (0.03-116). 22 pts had undergone prior autograft and 13 pts had prior CAR-T. The most common therapy given was chemoimmunotherapy (78%). 104/180 (58%) of pts were not eligible for any of the pivotal trials at time of relapse and only 37 (21%) were eligible for any 1 of 7 trials. No pts were eligible for all 7 trials (Table 1). SADAL (selinexor) criteria were most restrictive with a 14 week washout period from last therapy and allowing only 3-4 prior therapy lines. Failure due to organ function rates varied across the trials and details will be reported at the conference. Conclusion(s): Most rDLBCL pts are ineligible for registrational trials, causing difficulty applying results to routine care. Significant variation in rates of eligibility exists across landmark registration trials, causing challenges in comparisons in the absence of randomised studies. Standardised eligibility criteria are desperately needed for registrational studies and should more closely reflect the rDLBCL population being considered for these agents.