ABCL-367: Efficacy, Safety, and Patient-Reported Outcomes (PROs) of Treatments for Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL): A Systematic Literature Review (SLR)

Context Limited published SLRs exist on third-line and greater (3L+) treatment of R/R DLBCL, despite recent approvals of newer therapies. Objective To conduct an SLR evaluating the efficacy, safety, and PROs of therapies for 3L+ R/R DLBCL. Design SLR in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and European Union Health Technology Assessment requirements; publications prior to November 2020 in MEDLINE, MEDLINE In-Process, Embase, and Cochrane Library databases; supplemented by a gray literature search. Main Outcome Measures Efficacy, safety, and PROs. Results Post-screening of 9,901 records, 143 publications covering 40 studies were identified. Seven studies were reported as interventions of interest: chimeric antigen receptor T-cell therapy (CAR-T: 3), antibody–drug conjugates (ADC: 2), nuclear export inhibitor (S: 1), aza-anthracenedione analogue (P: 1), and chemo/chemoimmunotherapy (Ch: 2). Wide ranges of efficacy outcomes were reported. CAR-T reported overall response rates (ORR) of 52%–83%; median progression-free survival (mPFS) and overall survival (mOS) of 2.9–6.8 months (m) and 11.1–25.8 m, respectively. ADC: ORR 45%–48%; mPFS 5.1–9.5 m; mOS 9.5–12.4 m; S: ORR 28%; mPFS 2.6 m; mOS 9.1 m; P: ORR 37%; mPFS 5.3 m; mOS 10.2 m; and Ch: ORR 14%–18%; mPFS 2.6–3.7 m; mOS 4.7–7.6 m. Safety profiles varied. CAR-T: grade ≥ 3 treatment-emergent adverse events (TEAE) in 79%–98% of pts; grade ≥ 3 cytokine-release syndrome and neurological events in 2%–22% and 10%–32% of pts, respectively; treatment-related deaths in 2% (2/101) and 3% (7/267). With other treatments, the most common grade ≥3 AEs were neutropenia (ADC: 26%–46%; Ch: 19%–33%) and thrombocytopenia (ADC: 18%–41%; Ch: 12%–23%). Fatal AEs occurred in 20 pts (25%) in the ADC trial (n=80), with infection as the most common cause. Only two CAR-T trials presented PROs, using the Functional Assessment of Cancer Therapy-Lymphoma or the European Organisation for Research and Treatment of Cancer questionnaires. Health-related quality of life improvements were clinically meaningful in a notable proportion of pts, starting from month 1 or 3. Conclusions Despite availability of novel 3L+ therapies, a high unmet need exists for additional treatment options providing a favorable benefit/risk profile for R/R DLBCL pts. Limited PROs have been reported to date, and more studies characterizing pt outcomes are warranted to better elucidate benefit/risk for novel therapies.