IBCL-372: Efficacy, Safety, and Patient-Reported Outcomes (PROs) of Treatments for Relapsed/Refractory Follicular Lymphoma (R/R FL) in the Third-Line or Later (3L+) Setting: A Systematic Literature Review (SLR)

Abstract

Context There is no well-defined standard of care in 3L+ R/R FL. Recently, novel treatments were evaluated in trials or approved by regulators. Objective To conduct an SLR evaluating efficacy, safety, and PROs of treatments for 3L+ R/R FL. Design The SLR included publications prior to November 2020 in MEDLINE, MEDLINE In-Process, Embase, and Cochrane Library databases, with a supplemental gray literature search. Main Outcome Measures Efficacy, safety, and PROs. Results Post-screening of 7,330 records, 73 publications covering 28 studies were identified. Studies identified were characterized by line of treatment and response/survival rates; safety and PROs observed from the studies were described. Seven studies on 3L+ were reported as interventions of interest: anti-CD20 monoclonal antibodies (R: 1), PI3K inhibitors (PI3K: 4), EZH2 inhibitors (EZH2: 1), and chimeric antigen receptor T-cell therapy (CAR-T: 1). Efficacy varied. For R: Overall response rate (ORR) 38%; median duration of response (mDOR) 16.3 months (m). PI3K: ORR 43%–59%; mDOR 7.9–12.2 m; median progression-free survival (mPFS) 8.3–11.2 m. EZH2 for mutant/wild-type: ORR 69%/35%; mDOR 10.9 m/13.0 m; mPFS 13.8 m/11.1 m. CAR-T: ORR 94%; mDOR/mPFS not estimable. The most common adverse events (AEs) for R were grade 1/2 fever, chills, asthenia, and pruritus. PI3K: grade 3/4 treatment-emergent AEs (TEAE) rates were 65%–82% and included diarrhea, pneumonia, pyrexia, hyperglycemia, neutropenia, hypertension, anemia, and thrombocytopenia. Grade 5 events occurred in 6%–8% of patients (pts). EZH2: serious TEAEs occurred in 27%, with the most common events being sepsis, general physical health deterioration, and anemia; no AE-related deaths occurred. CAR-T: grade ≥ 3 AEs in 86% of pts, with the most common events being cytopenia and infection; grade ≥ 3 cytokine release syndrome and neurological events in 6% and 15%, respectively; grade 5 AEs in 2% of pts. Only 2 PI3Ks presented PRO data using the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) questionnaire. Both demonstrated favorable improvements in pts quality of life. Conclusions Despite the availability of novel 3L+ therapies, a high unmet need exists for additional treatment options providing a favorable benefit/risk profile for R/R FL pts. Limited PROs have been reported to date, and more studies characterizing patient outcomes are warranted to better elucidate benefit/risk for novel therapies.