An important treatment goal for patients with relapsed/refractory mantle-cell lymphoma (MCL) is to maintain and improve their functional status and well-being. Ibrutinib is a first-in-class, oral inhibitor of Bruton’s tyrosine kinase (BTK) that has demonstrated durable single-agent antilymphoma activity in patients with MCL, and is approved for treatment of patients who have received at least 1 prior therapy.1,2 RAY (MCL3001) is a phase 3, randomized study that compared ibrutinib versus temsirolimus in patients with relapsed and/or refractory MCL, and demonstrated a significant prolongation of progression-free survival that was accompanied by a favorable safety profile, which were reported separately at the meeting (Rule et al, Abstract 469). In this abstract, Hess and colleagues reported specifically on the analysis of treatment effect on lymphoma symptoms as assessed using the Functional Assessment of Cancer Therapy–Lymphoma (FACT-Lym) questionnaire lymphoma subscale in the trial.3
Of the 280 patients randomized on the trial, 253 patients (ibrutinib, n = 130; temsirolimus, n = 123) provided FACT-Lym lymphoma subscale responses at baseline. Median time to worsening (TTW) and time to clinically meaningful improvement (TTI) on the lymphoma subscale were also assessed; worsening was defined as a ?5-point decrease from baseline and clinically meaningful improvement as a ?5-point increase from baseline. Overall, ibrutinib therapy was associated with greater improvements and less worsening in lymphoma symptoms compared with temsirolimus. Ibrutinib therapy resulted in a statistically significant 73% reduction in the risk of worsening (P <.0001) compared with temsirolimus therapy, with median TTW of not reached versus 9.7 weeks. At a median follow-up of 20 months, median TTI was shorter for ibrutinib compared with temsirolimus (6.3 weeks vs 57.3 weeks; hazard ratio, 2.19; P <.0001). On the FACT-Lym lymphoma subscale, a lower proportion of patients showed worsening from baseline with ibrutinib versus temsirolimus (26.6% vs 51.8%), while a higher proportion showed clinically meaningful improvement from baseline (61.9% vs 35.5%). Based on the results of the RAY (MCL3001) trial, the authors concluded that the majority of patients treated with ibrutinib derived significant clinical benefit in terms of lymphoma symptom outcomes.
