Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Poster II
Hematology Disease Topics & Pathways:
Adult, Follicular Lymphoma, Diseases, Non-Hodgkin Lymphoma, Adverse Events, Study Population, Lymphoid Malignancies
Methods: A systematic literature review identified clinical trial publications for idelalisib (DELTA), duvelisib (DYNAMO), and copanlisib (CHRONOS-1 Part B) for use in an ITC with tazemetostat for 3L+ treatment of R/R FL. Matching-adjusted indirect comparison (MAIC) methodology was selected as all comparator trials were single-arm and individual patient data (IPD) were available for the tazemetostat E7438-G000-101 trial (n=99). Three MAIC analyses were conducted by weighting individual patients treated with tazemetostat to baseline characteristics reported from each comparator trial. FL subpopulation baseline characteristics and outcomes data were available for matching idelalisib (n=72); full trial mixed-NHL populations were reported for duvelisib (n=129, 64% FL) and copanlisib (n=142, 73% FL). Baseline characteristics for matching-adjustment were chosen using clinical advice, an evaluation of prognostic factors associated with outcomes, and published data availability. Characteristics included: age, ECOG performance status, disease stage, histology (tumor grade, transformed FL), number of prior lines of treatment, prior stem cell therapy, and refractory status (to last therapy). Only the tazemetostat trial included patients with grade 3b or transformed FL, or recorded EZH2 mutation status. Safety and efficacy outcome definitions were similar across trials. Primary safety outcomes included risk of any grade ≥3 treatment-emergent adverse event (TEAE), any treatment-emergent serious adverse event (TESAE), and TEAEs leading to dose reduction, drug discontinuation, or interruption. The primary efficacy outcome was objective response rate (ORR), reported across all trials. Rates of individual grade ≥3 TEAEs also were compared. Limitations of such indirect methods include inability to account for any unmeasured covariates that may be effect modifiers, and reductions in the effective sample size.
Results: After matching, all baseline characteristics were successfully balanced. Matched patients treated with tazemetostat had lower relative risk for all safety outcomes compared with all treatments, including any grade ≥3 TEAE (vs idelalisib: RR=0.45; vs duvelisib: RR=0.35; vs copanlisib: RR=0.37; all, P<0.001), any TESAE, and any TEAE leading to dose reduction, drug discontinuation, or interruption. These results were statistically significant (where comparator data were reported) for all but 2 safety outcomes (Figure). Several grade ≥3 TEAEs occurred at a significantly lower incidence with tazemetostat compared with matched patients treated with idelalisib, duvelisib, or copanlisib, including neutropenia (vs idelalisib: 3% vs 22%; vs duvelisib: 3% vs 25%; vs copanlisib: 4% vs 24%; all, P<0.05). The ORR was similar after matching for tazemetostat versus all treatments, with no statistically significant difference between therapies (vs idelalisib: 43% vs 56%, P=0.16; vs duvelisib: 48% vs 47%, P=0.91; vs copanlisib: 49% vs 61%, P=0.11).
Conclusion: More tolerable treatment options are needed for 3L+ treatment of R/R FL because patients in this setting are often elderly and have exhausted multiple prior lines of treatment. Results from this ITC indicate that, after adjusting for baseline population differences, tazemetostat addresses this unmet need, as it is associated with lower relative risk for safety outcomes versus idelalisib, duvelisib, or copanlisib while achieving similar efficacy outcomes.
Disclosures: Proudman: Analysis Group, Inc.: Consultancy. Nellesen: Analysis Group, Inc.: Consultancy. Gupta: Analysis Group, Inc.: Consultancy. Adib: Epizyme, Inc.: Consultancy; Alacrita: Current Employment. Yang: Epizyme, Inc.: Current Employment. Keith: Epizyme: Current Employment, Current equity holder in publicly-traded company. Mamlouk: Epizyme: Current Employment, Current equity holder in publicly-traded company.
See more of: Oral and Poster Abstracts