Advances in Clinical and Experimental Medicine

Adv Clin Exp Med
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ISSN 1899–5276 (print),   ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2019, vol. 28, nr 8, August, p. 1051–1057

doi: 10.17219/acem/99911

Publication type: original article

Language: English

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Creative Commons BY-NC-ND 3.0 Open Access

Ibrutinib discontinuation in patients with relapsed or refractory chronic lymphocytic leukemia treated in a compassionate use program: A report from the Polish Adult Leukemia Study Group (PALG)

Elżbieta Iskierka-Jażdżewska1,C,D,F, Bartosz Puła2,C,F, Agnieszka Szeremet3,B,F, Marek Hus4,B,F, Aleksandra Gołos2,B,F, Jadwiga Hołojda5,B,F, Weronika Piszczek6,B,F, Paweł Steckiewicz7,B,F, Małgorzata Wojciechowska8,B,F, Jan Maciej Zaucha9,10,B,F, Krzysztof Warzocha2,E,F, Krzysztof Jamroziak2,A,C,D,F

1 Department of Hematology, Copernicus Memorial Hospital, Łódź, Poland

2 Department of Hematology, Institute of Hematology and Transfusion Medicine, Warszawa, Poland

3 Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Poland

4 Department of Haematooncology and Bone Marrow Transplantation, Medical University of Lublin, Poland

5 Department of Hematology, Specialist District Hospital, Legnica, Poland

6 Department of Hematology, Copernicus Hospital, Toruń, Poland

7 Department of Hematology, Holycross Cancer Center, Kielce, Poland

8 Department of Hematology, Specialist District Hospital, Olsztyn, Poland

9 Department of Oncological Propaedeutics, Medical University of Gdańsk, Poland

10 Gdynia Oncology Center, Poland

Abstract

Background. Development of a novel class of drugs, the B-cell receptor-signaling inhibitors, including ibrutinib, has been a major achievement in the therapy of refractory or relapsed chronic lymphocytic leukemia (CLL). However, the CLL patients who have discontinued the ibrutinib treatment in clinical trials have been reported to have poor prognosis.
Objectives. In this retrospective study by the Polish Adult Leukemia Group (PALG), we analyzed the reasons for ibrutinib cessation and outcomes after discontinuing ibrutinib in refractory or relapsed CLL patients treated in a compassionate use program in Poland.
Material and Methods. Polish CLL patients were included if they discontinued ibrutinib for any reason. The clinical data on the course of ibrutinib treatment was collected anonymously using electronic Case Report Forms (CRFs). The causes of discontinuation of ibrutinib as reported by the treating physicians were analyzed.
Results. Thirty-seven patients who discontinued ibrutinib were identified. The median duration of ibrutinib treatment in this group was 4.4 months (range: 0.2–25.2). The main reason for discontinuing ibrutinib was adverse events (n = 20, 54%), while 14 (38%) patients discontinued therapy due to disease progression and 3 (8%) due to other causes. The most common treatment complications that led to ibrutinib cessation were severe respiratory tract infections (9 patients, 24%). In the group discontinuing ibrutinib for progressive disease, 11 patients progressed with untransformed CLL, while in 3 patients, a rare type of Richter transformation to Hodgkin’s lymphoma was diagnosed. Twenty-nine patients (78%) died during the follow-up period, and median overall survival (OS) reached 2.0 months (95% CI = 0.8–5.5 months). Importantly, no significant survival difference was detected between patients who discontinued ibrutinib due to disease progression and due to adverse events.
Conclusion. The results of this analysis indicate that ibrutinib discontinuation in relapsed or refractory CLL is associated with poor prognosis regardless of the reason for ibrutinib cessation.

Key words

tyrosine kinase inhibitor, chronic lymphocytic leukemia, ibrutinib

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