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. Herein we report 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 in the study between May 2014 and May 2015. The median age was 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 a median follow-up of 10.2 months, the 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 proportional regression hazards model. Ibrutinib was well tolerated. Hematomas occurred in 46% of patients without any major bleeding. Seven patients had Richter's transformation. This real-world analysis on consecutive chronic lymphocytic leukemia patients from a well-defined geographical region shows the efficacy and safety of ibrutinib to be 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 in future with regards to new agents and new indications in chronic lymphocytic leukemia. IntroductionChronic lymphocytic leukemia (CLL), the most common leukemia in adults, is characterized by a clonal expansion of CD5 + and CD23 + B-lymphocytes which accumulate in blood, bone marrow and lymphoid tissues. Chemoimmunotherapy is the standard first-line treatment, but patients with del(17p) or TP53 gene muta- The CLL cell receives survival and proliferation signals from the microenvironment, and the B-cell receptor (BCR) is a key factor in this interaction. Bruton´s tyrosine kinase (BTK) is a non-receptor tyrosine kinase and plays a crucial role in BCR signalling. Ibrutinib is an oral, selective and irreversible inhibitor of BTK. It binds to the cysteine-481 amino acid of the BTK enzyme. Real -world results of ibrutinib in patients with5 Next-generation BTK inhibitors are under clinical development with promising early results. 6In the first phase 2 study of ibrutinib, 71% of patients with relapsed or refractory CLL achieved a partial response (PR) according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria, 7 and an additional 18% of patients had PR with lymphocytosis (PR-L). 8 The response was independent of clinical and genomic risk factors including del(17p). The 3-year followup of this study reported no late occurring toxicity, and progression was...

Long-term real-world results of ibrutinib therapy in patients with relapsed or refractory chronic lymphocytic leukemia: 30-month follow up of the Swedish compassionate use cohort LETTERS TO THE EDITOR

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