Heterogeneity of Populations and Outcomes for Patients with Relapsed or Refractory DLBCL

A plethora of clinical trials and new therapies have led to the rapidly evolving treatment landscape of relapsed or refractory diffuse large B-cell lymphoma (DLBCL). In an effort to assess the impact of baseline characteristic variations on overall response rate (ORR) in this patient population, a systematic literature review of clinical trials was conducted. Once screened and deemed suitable for study inclusion, baseline patient characteristics and clinical outcomes were extracted and evaluated.

A total of 21,130 abstracts and 2306 full texts—identified through MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) using Ovid—were screened for inclusion. Eighteen published studies—from 17 clinical trials, mostly single arm—were included. Of the 18 studies, 3 evaluated chimeric antigen receptor T-cell (CAR-T) therapies, 3 evaluated rituximab plus gemcitabine-oxaliplatin, 3 evaluated rituximab plus bendamustine (R-Benda), and 2 evaluated polatuzumab vedotin plus R-Benda; the remaining 7 studies evaluated guideline-directed therapies, including tafasitamab plus lenalidomide, loncastuximab, and selinexor.

Among the 18 studies, key baseline patient characteristics were shown to vary greatly. The percentage of patients with primary refractory DLBCL ranged from 0% to 69%, and the percentage of patients refractory to their last line of therapy ranged from 12% to 100%. Large differences were also seen among studies in the percentage of patients with ≥2 prior lines of therapy (14%-100%), ≥3 prior lines of therapy (0%-64%), International Prognostic Index (IPI) score ≥3 (23%-73%), Eastern Cooperative Oncology Group (ECOG) score of 0-1 (67%-100%), and Ann Arbor stage III/IV (50%-90%). Median age ranged from 56 to 74 years and reported ORRs varied considerably at 25%-83%.

Within this study, correlation coefficients—interpreted as moderate (0.40-0.69); strong (0.70-0.89); very strong (0.90-1.00)—were calculated between baseline patient characteristics and reported ORR. Moderate-to-strong negative correlations were found to exist between ORR and median age, IPI ≥3, prior anti-CD20 exposure, and primary refractory disease.

These findings strongly suggest that differences in baseline patient characteristics greatly contribute to the variability of ORR findings across studies in relapsed or refractory DLBCL; therefore, care should be taken to consider baseline patient characteristics when evaluating efficacy data in this population, particularly when conducting cross-trial comparisons.

Source:

Lozano-Ortega G, Miller S, Mutebi A, et al. A systematic literature review of trial outcomes and population heterogeneity for relapsed or refractory diffuse large B-cell lymphoma patients who are ineligible or have experienced transplant. Presented at: 2022 Academy of Managed Care Pharmacy Nexus Annual Meeting; October 11-14, 2022; National Harbor, MD. Poster C38.