According to a study published in Lancet Oncology, 90 percent of patients (n=28/31) with Waldenström macroglobulinemia (WM) responded to treatment with ibrutinib 420 mg, including 22 (71%) major responses.
Meletios A. Dimopoulos, MD, from the National and Kapodistrian University of Athens School of Medicine in Greece, and authors led the phase II, open-label sub-study of the larger iNNOVATE trial – a randomized, placebo-controlled study comparing ibrutinib plus rituximab with rituximab plus placebo for patients with WM. The study took place at 19 sites in 11 countries between August 2014 and February 2015. The current analysis examined data from 31 patients (mean age = 67 years; range = 58-74 years) with WM who were refractory to rituximab and had received a median of four previous therapies.
Patients received ibrutinib 420 mg, and, after a median follow-up of 18.1 months (range = 17.5-18.9 months), the progression-free survival rate was 86 percent (95% CI 66-94) and the overall survival rate was 97 percent (95% CI 79-100).
Baseline median hemoglobin levels (10.3 g/dL; range = 9.3-11.7 g/dL) increased to 11.4 g/dL (range = 10.9-12.4 g/dL) after four weeks of treatment and reached 12.7 g/dL (range = 11.8-13.4 g/dL) by week 49.
Seventeen patients had MYD88 mutations, and 88 percent (n=15) responded to ibrutinib.
Sixty-five percent of patients (n=20) experienced grade ≥3 adverse events (AEs), including neutropenia (n=4; 13%), hypertension (n=3; 10%), anemia (n=2; 6%), thrombocytopenia (n=2; 6%), and diarrhea (n=2; 6%). Five patients (16%) discontinued treatment due to disease progression (n=3) and AEs (n=2). Thirty patients (97%) were alive at the end of the study.
The study is limited by its small patient population. In addition, “The sub-study was not prospectively powered for statistical comparisons, and as such, all the analyses are descriptive in nature,” the authors noted.
Source: Dimopoulos MA, Trotman J, Tedeschi A, et al. Ibrutinib for patients with rituximab-refractory Waldenström’s macroglobulinaemia (iNNOVATE): an open-label substudy of an international, multicentre, phase 3 trial. Lancet Oncol. 2016 December 9. [Epub ahead of print]