Patients with Waldenström’s macroglobulinemia (WM) frequently experience anemia and fatigue, which can adversely affect their quality of life. In patients with rituximab-refractory WM, single-agent ibrutinib induced meaningful improvements in patient-reported outcomes.1 In prior reports from the iNNOVATE study, the combination of ibrutinib and rituximab produced higher rates of sustained hemoglobin improvement and meaningful improvements in patient-reported outcomes compared with placebo plus rituximab.2 Hence, ibrutinib is approved in the United States as single-agent therapy and in combination with rituximab for patients with WM. At the ASCO 2019 Annual Meeting, researchers reported detailed patient-reported outcomes analyses from iNNOVATE.
Patients with symptomatic WM requiring therapy were randomized to 420 mg daily of oral ibrutinib and rituximab or placebo and rituximab. In both arms, the rituximab dosing regimen was 375 mg/m2 per week given intravenously at weeks 1 through 4 and at weeks 17 through 20. Patient-reported outcome measures included Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Functional Assessment of Cancer Therapy-Anemia (FACT-An) total score (TS) and anemia subscale score (AS), EQ-5D-5L visual analog scale (EQ-VAS), and utility score.
Of the 75 patients randomized to each arm of the study, the most common reasons for initiating therapy were fatigue (61%), constitutional symptoms (32%), and anemia (32%). Baseline patient-reported outcome scores were comparable in both arms. At a median follow-up of 26.5 months, numerically more patients showed clinically meaningful improvement in FACIT-F (69% vs 57%), as well as FACT-An TS (73% vs 59%) and AS (64% vs 48%), with ibrutinib plus rituximab than with rituximab plus placebo. The median time to improvement in patient-reported outcomes was relatively brief (1-2 months) in both arms. A correlation analysis conducted at week 25 showed that changes in immunoglobulin M (IgM) levels correlated with FACIT-F, FACT-An TS, FACT-An AS, and EQ-VAS for ibrutinib plus rituximab and with FACIT-F and FACT-An TS for rituximab plus placebo. Changes in hemoglobin levels correlated with FACIT-F, FACT-An TS, and FACT-An AS for patients receiving ibrutinib plus rituximab; no meaningful correlations were observed for patients receiving placebo plus rituximab.
Clinical response and improvements in IgM and hemoglobin levels with ibrutinib and rituximab are consistent with prior reports showing clinically meaningful improvement in patient-reported outcomes versus rituximab.
Abstract 8018; Tedeschi A, et al.
- Trotman J, et al. Patient-reported outcomes with ibrutinib: substudy of iNNOVATE™ for Waldenstrom macroglobulinemia. EHA 2017. Abstract E1246.
- Dimopoulos MA, et al. Phase 3 trial of ibrutinib plus rituximab in Waldenström’s macroglobulinemia. N Engl J Med. 2018;378:2399-2410.