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Observational Study
. 2021 Jul;100(7):1723-1732.
doi: 10.1007/s00277-021-04507-x. Epub 2021 May 4.

Clinical outcomes in patients with Philadelphia chromosome-positive leukemia treated with ponatinib in routine clinical practice-data from a Belgian registry

Timothy Devos  1 , Violaine Havelange  2 , Koen Theunissen  3 , Stef Meers  4 , Fleur Samantha Benghiat  5 , Alain Gadisseur  6 , Gaëtan Vanstraelen  7 , Hélène Vellemans  8 , Benjamin Bailly  9 , Nikki Granacher  10 , Philippe Lewalle  11 , Ann De Becker  12 , Koen Van Eygen  13 , Mia Janssen  14 , Agnes Triffet  15 , Inge Vrelust  16 , Dries Deeren  17 , Dominiek Mazure  18 , Julie Bekaert  19 , Michael Beck  20 , Dominik Selleslag  21
Affiliations
Observational Study

Clinical outcomes in patients with Philadelphia chromosome-positive leukemia treated with ponatinib in routine clinical practice-data from a Belgian registry

Timothy Devos et al. Ann Hematol. 2021 Jul.

Abstract

Data on clinical use of ponatinib are limited. This prospective registry aimed to evaluate outcomes of ponatinib treatment in routine practice over 3 years (2016-2019) in Belgium (NCT03678454). Patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) were treated with ponatinib per current label. Fifty patients (33 CML and 17 Ph+ ALL) were enrolled. Fifty-five percent of CML and 29% of Ph+ ALL patients had received ≥3 prior tyrosine kinase inhibitors (TKIs). Reasons for starting ponatinib were intolerance (40%), relapse or refractoriness (28%) to previous TKIs, progression (16%), or T315I mutation (16%). Median follow-up was 15 months for CML and 4.5 months for Ph+ ALL patients. Best response was a major molecular response in 58% of CML and 41% of Ph+ ALL patients. Of 20 patients who started ponatinib due to intolerance to previous TKIs, 9 (64%) CML and 4 (67%) Ph+ ALL achieved a major molecular response. Three-year estimates of overall survival were 85.3% and 85.6%, respectively, in CML and Ph+ ALL patients; estimated progression-free survival was 81.6% and 48.9%. Adverse reactions were reported in 34 patients (68%); rash (26%) and dry skin (10%) were most common. Reported cardiovascular adverse reactions included vascular stenosis (3), arterial hypertension (2), chest pain (1), palpitations (1), and vascular occlusion (1). This Belgian registry confirms results from the PACE clinical trial and supports routine ponatinib use in CML and Ph+ ALL patients who are resistant or intolerant to previous TKIs or with the T315I mutation.

Keywords: Chronic myeloid leukemia; Philadelphia chromosome-positive acute lymphoblastic leukemia; Ponatinib; Registry; Routine clinical practice.

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Conflict of interest statement

KT reports membership of advisory boards from multiple pharmaceutical companies. BB reports research funding from Incyte Biosciences Benelux BV. ADB reports ad hoc membership of advisory boards from multiple pharmaceutical companies. DD reports consultancy, honoraria, membership of Board of Directors or advisory committees, and research funding from multiple pharmaceutical companies. DS reports consultancy and travel expenses from Incyte Biosciences Benelux BV. JB and MB are employees of Incyte Biosciences. There are no relationships to disclose for TD, VH, SM, FSB, AG, GV, HV, NG, PL, KVE, MJ, AT, IV, and DM.

Figures

Fig. 1
Fig. 1
Study design. D, day; M, month; CML, chronic myeloid leukemia; Ph+ ALL, Philadelphia chromosome-positive acute lymphoblastic leukemia; D0, the start of reimbursement of ponatinib in Belgium, i.e., March 1, 2016
Fig. 2
Fig. 2
Reasons for starting ponatinib treatment. CML, chronic myeloid leukemia; Ph+ ALL, Philadelphia chromosome-positive acute lymphoblastic leukemia; intolerant, those who started ponatinib due to intolerance to previous tyrosine kinase inhibitors (TKIs); non-intolerant, those who started ponatinib due to reasons other than intolerance to previous TKIs (progression, T315I mutation, relapse or refractoriness). Refractoriness to previous TKI in this figure included absence of response, primary refractoriness, and hematological or cytogenetic relapse on previous TKI. Percentages may not add up to 100 due to rounding
Fig. 3
Fig. 3
Swimmer plot displaying treatment duration, treatment modification, and outcome for each patient. Each bar represents an individual patient. Patients with CML were in chronic phase, except for 3 indicated patients: orange circle, blastic myeloid phase; purple circle, accelerated phase; grey circle, blastic lymphoid phase; AE, adverse event; CCyR, complete cytogenetic response; MMR, major molecular response; alloSCT, allogeneic stem cell transplantation; TKI, tyrosine kinase inhibitor
Fig. 4
Fig. 4
Best response to treatment in patients with a CML and b Ph+ ALL (overall, intolerant and non-intolerant patients). CCyR, complete cytogenetic response; CML, chronic myeloid leukemia; MMR, major molecular response; N, number of patients; Ph+ ALL, Philadelphia chromosome-positive acute lymphoblastic leukemia. *1 patient had achieved CCyR before starting treatment with ponatinib. Of note, 2 (6%) patients with CML and 4 (24%) patients with Ph+ ALL did not have measurable responses to treatment
Fig. 5
Fig. 5
Kaplan-Meier estimates of overall survival and progression-free survival in a patients with CML (overall, intolerant and non-intolerant patients) and b patients with Ph+ ALL (overall, intolerant and non-intolerant patients). CML, chronic myeloid leukemia; Ph+ ALL, Philadelphia chromosome-positive acute lymphoblastic leukemia; TKI, tyrosine kinase inhibitor; OS, overall survival; PFS, progression-free survival
Fig. 6
Fig. 6
The most frequently reported adverse reactions. N, number of patients
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