1. The role of ponatinib in adult BCR-ABL1 positive acute lymphoblastic leukemia after allogeneic transplantation: a real-life retrospective multicenter study
- Author
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Uros Markovic, Ernesto Vigna, Francesco Grimaldi, Giulia Palazzo, Antonio M. Risitano, Massimo Martino, Maria Cristina Pirosa, Giuseppe Milone, Stefania Stella, Giovanni Pisapia, Angelo Curto Pelle, Raffaele Palmieri, Luca Scalise, Francesco Di Raimondo, Stefania Tringali, Salvatore Leotta, Giulio Antonio Milone, Valerio Leotta, Fausto Palmieri, Paola Carluccio, Mary Ann Di Giorgio, Giorgina Specchia, Anna Bulla, and Mario Annunziata
- Subjects
Male ,bcr-abl ,Fusion Proteins, bcr-abl ,Salvage therapy ,Tyrosine-kinase inhibitor ,chemistry.chemical_compound ,0302 clinical medicine ,Recurrence ,hemic and lymphatic diseases ,Secondary Prevention ,Philadelphia Chromosome ,Adjuvant ,Ph’+acute lymphoblastic leukemia ,Hematology ,Ponatinib ,Hematopoietic Stem Cell Transplantation ,Imidazoles ,General Medicine ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Combined Modality Therapy ,Pyridazines ,Italy ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Acute Disease ,Cohort ,Toxicity ,Female ,Homologous ,Adult ,medicine.medical_specialty ,Allogeneic transplantation ,medicine.drug_class ,Chemoprevention ,Young Adult ,03 medical and health sciences ,Internal medicine ,medicine ,Chemotherapy ,Humans ,Transplantation, Homologous ,Retrospective Studies ,Salvage Therapy ,Transplantation ,business.industry ,Fusion Proteins ,Survival Analysis ,chemistry ,business ,030215 immunology - Abstract
The experience of third-generation tyrosine kinase inhibitor ponatinib treatment in Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph'+ ALL) patients post-allogeneic transplantation is limited. We retrospectively collected data on 25 Ph'+ ALL patients who were started on ponatinib after allogeneic transplantation between July 2015 and July 2019 from nine transplantation centers in Italy. Ponatinib was given in prophylaxis in five (20%), as pre-emptive treatment in seven (28%), and as salvage therapy in thirteen (52%) patients. It was combined with donor leukocyte infusions in ten patients. Half of the patients (12/25) harbored T315I mutation of BCR/ABL1, while in the remaining mutational analysis was negative or not performed. Among the 20 patients who received ponatinib as pre-emptive/salvage treatment, complete molecular response was achieved in 15 (75%) patients. Estimated overall survival at 2-year post-initiation of treatment in the whole cohort was 65% (respectively 60%, 60%, and 78% for the prophylaxis, pre-emptive, and salvage therapy groups). In patients with T315I-positive mutational status, the estimated 2-year survival was 40%. Fourteen patients (56%) experienced toxicity, requiring temporary or definitive suspension of treatment. In conclusion, treatment of Ph'+ ALL patients with ponatinib after transplantation is effective, although the question of adequate drug dose and treatment duration remains unanswered.
- Published
- 2021