Salvage and bridging to allogeneic hematopoietic cell transplantation with ponatinib in patients with relapsed or refractory Philadelphia chromosome-positive leukemia
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Abstract
A single-center retrospective study was performed with consecutive patients who received salvage therapy using ponatinib for the aim of allogeneic hematopoietic cell transplantation (HCT) for relapsed or refractory Ph-leukemia between January 2017 and July 2018. A total of ten patients—seven with Ph-acute lymphoblastic leukemia (ALL) and three with chronic phase (CP)/accelerated phase chronic myeloid leukemia (CML)—were eligible. Eight patients had a history of a single tyrosine kinase inhibitor (TKI) use prior to ponatinib. Any mutation of the tyrosine kinase domain was detected in eight patients, including seven of T315I. The median dose of ponatinib was 15 mg with a median duration of 7 weeks (range 4–23 weeks). The median duration from the start of ponatinib to HCT was 54 days (range 35–175 days). Hematological remission was obtained in five Ph-ALL patients. Maintenance therapy of ponatinib was applied to five patients. No vascular occlusion event has occurred over this series of treatments. Salvage therapy with low-dose ponatinib appears to be safe and effective in patients with relapsed or refractory Ph-leukemia, which may immediately bridge to HCT.
Keywords
Ponatinib Philadelphia-positive leukemia Transplantation Bridging therapyNotes
Compliance with ethical standards
Conflict of interest
There are no conflicts of interest to declare.
References
- 1.Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre P, Paquette R, Chuah C, et al. Phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med. 2013;369(19):1783–96.CrossRefGoogle Scholar
- 2.Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016;375(8):740–53.CrossRefGoogle Scholar
- 3.Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371(16):1507–17.CrossRefGoogle Scholar
- 4.Zabriskie MS, Eide CA, Tantravahi SK, Vellore NA, Estrada J, Nicolini FE, et al. BCR-ABL1 compound mutations combining key kinase domain positions confer clinical resistance to ponatinib in Ph chromosome-positive leukemia. Cancer Cell. 2014;26(3):428–42.CrossRefGoogle Scholar
- 5.Miller GD, Bruno BJ, Lim CS. Resistant mutations in CML and Ph(+)ALL—role of ponatinib. Biologics. 2014;8:243–54.Google Scholar
- 6.Tojo A, Kyo T, Yamamoto K, Nakamae H, Takahashi N, Kobayashi Y, et al. Ponatinib in Japanese patients with Philadelphia chromosome-positive leukemia, a phase 1/2 study. Int J Hematol. 2017;106(3):385–97.CrossRefGoogle Scholar
- 7.Jabbour E, Kantarjian H, Ravandi F, Thomas D, Huang X, Faderl S, et al. Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: a single-centre, phase 2 study. Lancet Oncol. 2015;16(15):1547–55.CrossRefGoogle Scholar
- 8.Sasaki K, Jabbour EJ, Ravandi F, Short NJ, Thomas DA, Garcia-Manero G, et al. Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: a propensity score analysis. Cancer. 2016;122(23):3650–6.CrossRefGoogle Scholar
- 9.Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, et al. European Leukemia Net recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122(6):872–84.CrossRefGoogle Scholar
- 10.Nishiwaki S, Imai K, Mizuta S, Kanamori H, Ohashi K, Fukuda T, et al. Impact of MRD and TKI on allogeneic hematopoietic cell transplantation for Ph + ALL: a study from the adult ALL WG of the JSHCT. Bone Marrow Transpl. 2016;51(1):43–50.CrossRefGoogle Scholar
- 11.Assi R, Kantarjian H, Short NJ, Daver N, Takahashi K, Garcia-Manero G, et al. Safety and efficacy of blinatumomab in combination with a tyrosine kinase inhibitor for the treatment of relapsed Philadelphia chromosome-positive leukemia. Clin Lymphoma Myeloma Leuk. 2017;17(12):897–901.CrossRefGoogle Scholar
- 12.Robinson S, Levy Y, Maisel C, Tong AW. Haematological complete remission by ponatinib and bortezomib in a patient with relapsed, Ph+ pre-B acute lymphoblastic leukaemia. BMJ Case Rep. 2014;2014:bcr2014203894.CrossRefGoogle Scholar
- 13.DeFilipp Z, Langston AA, Chen Z, Zhang C, Arellano ML, El Rassi F, et al. Does post-transplant maintenance therapy with tyrosine kinase inhibitors improve outcomes of patients with high-risk philadelphia chromosome-positive leukemia? Clin Lymphoma Myeloma Leuk. 2016;16(8):466–71.CrossRefGoogle Scholar
- 14.Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre PD, Paquette R, Chuah C, et al. Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial. Blood. 2018;132:393–404.CrossRefGoogle Scholar
- 15.Dorer DJ, Knickerbocker RK, Baccarani M, Cortes JE, Hochhaus A, Talpaz M, et al. Impact of dose intensity of ponatinib on selected adverse events: multivariate analyses from a pooled population of clinical trial patients. Leuk Res. 2016;48:84–91.CrossRefGoogle Scholar
- 16.Tefferi A. Upfront low-dose ponatinib (15 mg/day) for multi-TKI resistant chronic myeloid leukemia. Hematol Oncol. 2018;36(4):718–20.CrossRefGoogle Scholar
- 17.Iurlo A, Cattaneo D, Orofino N, Bucelli C, Molica M, Breccia M. Low-dose ponatinib in intolerant chronic myeloid leukemia patients: a safe and effective option. Clin Drug Investig. 2018;38(5):475–6.CrossRefGoogle Scholar
- 18.Abumiya M, Miura M, Takahashi N. Therapeutic drug monitoring of ponatinib using a simple high-performance liquid chromatography method in Japanese patients. Leuk Res. 2018;64:42–5.CrossRefGoogle Scholar