Geriatric Assessment (GA) Measures and Patient-Reported Outcomes (PROs) Among Older Adults Treated in a Phase 1b Study for Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)

Introduction The measurement, analysis, and communication of treatment-related symptoms and their impact on the functioning of individuals in clinical trials is an area of interest to the medical community, the Food and Drug Administration and other regulatory agencies. Inclusion of GAs and PROs in early phase trials can characterize the heterogeneity of aging and guide development of therapies to benefit older adults. Despite evidence that GAs and PROs are feasible and predictive of outcome, few early phase trials have integrated them to inform on treatment tolerance. The aim of this analysis is to describe changes in GAs and PROs among older adults with R/R AML in a Phase 1b trial of BCL2 inhibitor venetoclax (Ven) with either MEK inhibitor cobimetinib (cobi) or MDM2 antagonist idasanutlin (idasa) (NCT02670044). Methods Patients (pts) aged ≥60 yrs who were ineligible for cytotoxic therapy/allogeneic stem cell transplant were enrolled in this open-label, multicenter study, designed to evaluate the safety, tolerability, and efficacy of Ven+cobi/idasa in R/R or secondary AML. GA measures were Short Physical Performance Battery (SPPB; gait speed, balance tests, chair stands), Hematopoietic Cell Transplant-Comorbidity Index (HCT-CI) and Short Blessed Orientation Test (SBOT). Treatment-related symptoms were assessed via the PRO version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), administered electronically throughout treatment. GAs were administered at screening, Cycle (C) 2 Day (D) 1, C3D1, and C7D1; PRO-CTCAE was administered at C1D1, weekly during C1, for the first 3 weeks of C2 and C3, and monthly starting at C4D1. Mean GA scores were calculated over time for each treatment arm and pt-level heatmaps were created. The ‘frequency’, ‘severity’, ‘interference’, and ‘presence’ of PRO-CTCAE symptoms were reported at each assessment, with a longitudinal analysis to understand how symptoms changed over the course of treatment. Results As of April 6 2018, 64 pts had been treated with either Ven+cobi or Ven+idasa. Baseline characteristics were comparable between arms; respectively: median age, 72, 74 yrs; ECOG performance status 0-1, 83%, 82%; refractory disease, 63%, 56%. GA and PRO data were available in 52 and 38 pts, respectively. Screening of GAs identified a physically frail (mean SPPB score