Real-world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: data from 95 consecutive patients treated in a compassionate use program. A study from the Swedish Chronic Lymphocytic Leukemia Group

Abstract

Ibrutinib, a Bruton's tyrosine kinase inhibitor is approved for relapsed/refractory and del(17p)/TP53 mutated chronic lymphocytic leukemia. Discrepancies between clinical trials and routine healthcare are commonly observed in oncology. We report here real-world results for 95 poor-prognosis Swedish patients treated with ibrutinib in a compassionate-use program. Ninety-five consecutive patients (93 chronic lymphocytic leukemia, 2 small lymphocytic leukemia) were included between May 2014 and May 2015. Median age; 69 years, 63% had del(17p)/TP53 mutation, 65% had Rai stage III/IV, 28% had lymphadenopathy ≥10cm. Patients received ibrutinib 420 mg once-daily until progression. At median follow-up of 10.2 months, overall response rate was 84% (consistent among subgroups) and 77% remained progression-free. Progression free survival and overall survival were significantly shorter in patients with del(17p)/TP53 mutation (p=0.017 and p=0.027, log-rank test); no other factor was significant in Cox's multivariate regression analysis. Ibrutinib was well tolerated. Hematomas occurred in 46% of patients without any major bleeding. Seven patients had Richter transformation. This real-world analysis on consecutive chronic lymphocytic leukemia patients from a well-defined geographical region shows efficacy and safety of ibrutinib similar to that of pivotal trials. Yet, del(17p)/TP53 mutation remains a therapeutic challenge. Since not more than half of our patients would have qualified for the pivotal ibrutinib trial (RESONATE), our study emphasizes that real-world results should be carefully considered onwards regarding new agents and new indications in chronic lymphocytic leukemia.