Toxicity and Outcomes of Ibrutinib in Chronic Lymphatic Leukemia-Real-World Results from the Study of 215 Patients in Argentina

Abstract

Different pivotal works allowed the approval of ibrutinib as a CLL treatment, both in the first line and in relapsed/refractory patients, the adverse effects differ from conventional chemotherapy, the discontinuation rate was 10%, but in different real-life studies, showed a higher number of complications and medication suspension rates of 40 to 50%. To know the reality of the use of ibrutinib in CLL in our environment, we designed this work with the objectives of evaluating the safety profile of the drug with the description of the adverse effects, their incidence, and their severity. The clinical efficacy will also be studied with the determination of the response achieved, calculation of overall survival (OS) and progression-free survival. Also as an additional objective, the discontinuation rate and its causes will be obtained. A total of 215 patients in 26 centers throughout the country were retrospectively analyzed. 189 patients (88%) had a global response, and the majority 58% achieved a partial response. The 5-year overall survival was 60%, with no difference between patients with different numbers of previous lines. The progression-free survival of the entire group was 5.06 years. 44.7% of the population, presented at least 1 adverse effect. The most frequent ones were: bleeding, thrombocytopenia, pneumonia and diarrhea. Others presented: anemia, neutropenia, infections, AF, HTA, arthralgia, rash, opportunistic infections. Most adverse events were mild to moderate in grade and generally occurred within the first 6 months. The main cause of treatment suspension was the appearance of adverse effects, 37 patients had to suspend it, 27 due to adverse effects (72.97%). In our work, we found that ibrutinib, as a single agent, has outstanding activity in CLL, with a significant percentage of overall responses, even in patients with several lines of prior treatment. Most of the adverse effects were of a mild to moderate degree. The cardiovascular effects of TKI, HBP, and AF, are in percentages similar to those reported in other studies. If we analyze the percentage of treatment discontinuation, which is 17%, mostly due to adverse effects, this finding is similar to pivotal studies. In conclusion, our real-life study confirms the important activity of ibrutinib in patients with CLL, in the first line and relapses, highlighting the low percentage of treatment discontinuation in our environment. We believe our work reflects the real life and daily care of patients with CLL, under treatment with ibrutinib in our environment.