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. 2016 Dec;101(12):1573-1580.
doi: 10.3324/haematol.2016.144576. Epub 2016 May 19.

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

Maria Winqvist  1   2 , Anna Asklid  2   3 , P O Andersson  4 , Karin Karlsson  5 , Claes Karlsson  1   2 , Birgitta Lauri  6 , Jeanette Lundin  1   2 , Mattias Mattsson  7 , Stefan Norin  1 , Anna Sandstedt  8 , Lotta Hansson  9   2 , Anders Österborg  1   2
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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

Maria Winqvist et al. Haematologica. 2016 Dec.

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 health-care 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.

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Figures

Figure 1.
Figure 1.
Time kinetics of recovery of blood counts. Hemoglobin concentration (A) and platelet count (B) during ibrutinib therapy in patients with baseline cytopenias. Mean +/− SEM at each timepoint is shown.
Figure 2.
Figure 2.
Overall survival (OS) and progression-free survival (PFS). Kaplan-Meier curves of PFS in (A) all patients and (B) patients with or without del(17p)/TP53 mutation and OS in (C) all patients and (D) patients with or without del(17p)/TP53 mutation.
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