Tyrosine Kinase Inhibitor (TKI) Discontinuation in Non-Allografted Ph+ Acute Lymphoblastic Leukemia Patients, a Campus ALL Real-Life Study
Introduction. Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) patients are commonly treated with tyrosine kinase inhibitors (TKI) in combination with either steroids, chemotherapy and more recently also immunotherapy. In the past, allogeneic transplant (SCT) was considered the only cura...
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Veröffentlicht in: | Blood 2023-11, Vol.142 (Supplement 1), p.2835-2835 |
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Sprache: | eng |
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Zusammenfassung: | Introduction. Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) patients are commonly treated with tyrosine kinase inhibitors (TKI) in combination with either steroids, chemotherapy and more recently also immunotherapy. In the past, allogeneic transplant (SCT) was considered the only curative option; however, with the introduction of more potent TKIs as well as immunotherapy this milestone is nowadays debated, mostly for patients who achieve a molecular response. Moreover, as in chronic myeloid leukemia (CML), it is becoming relevant to understand if patients may over time discontinue TKI treatment. For this purpose, it is pivotal to report the outcome of Ph+ ALL patients who, for any reason, stopped TKI treatment.
Patients and Methods. Forty-seven adult Ph+ ALL patients treated since 1 January 2000, and who did not undergo a SCT, were retrospectively collected from 12 Italian centers participating to the Campus ALL network. Their treatment plan included a TKI +/- chemotherapy according to the center current practice and/or according to the ongoing national trial they were enrolled in. The median age was 63 years (20-84), 20 patients (43%) were males, 30 patients harbored a p190 transcript, 15 a p210 transcript and 2 had both transcripts. Twenty-six patients were treated within a trial, while 21 were off-protocol. For 32 patients, induction was based only on a TKI plus steroids, whereas the remaining 15 received a combination of a TKI plus chemotherapy (in 3 cases high intensity protocols such as the NILG (Northern Italian Leukemia Group) and HCVAD regimens, in 12 low dose chemotherapy). The reasons not to transplant patients were: donor unavailability (5), clinical decision, mainly due to age/unfitness (30), patient's refusal (4), and achievement of a molecular response (i.e. at least BCR-ABL/ABL ≤0.01%) (8). The median follow-up was 60 months, with a median overall survival (OS) not reached at the last follow-up and a median disease-free survival (DFS) of 12 years. At the last follow-up, 12/47 patients had experienced a relapse. At the end of the induction (i.e. after 3 months, at a median of +82 days, from treatment initiation), 27 patients had achieved a molecular response. Overall. a molecular response was obtained in 40/46 pts (data not available for 1 case) after a median of 5 month, and was associated with a significantly lower hazard of disease recurrence (HR=0.057, 95% CI: 0.006-0.51, p=0.011) after adjusting for gender, fusion protein |
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ISSN: | 0006-4971 1528-0020 |
DOI: | 10.1182/blood-2023-187668 |