Session: 612. Acute Lymphoblastic Leukemias: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, ALL, Clinical Practice (Health Services and Quality), Diseases, Lymphoid Malignancies, Minimal Residual Disease
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, association with chemotherapy, CMR at 3 months.
Results. TKI treatment was discontinued in 14 of the 47 patients evaluated. The reasons for discontinuation were either toxicity (6) or clinical/patient decision (8). Eight patients harbored a p190 transcript, 5 a p210 transcript and 1 carried both. At the time of discontinuation, the median age was 75 years (23-87) and patients had been on a TKI for a median of 57.5 months (8-160) prior to stopping treatment. For these cases, the median WBC at diagnosis were 8.6 x 109/l (2.1-306 x 109/l). In 7 patients the first TKI used was imatinib, in 3 dasatinib, in 3 ponatinib and in 1 nilotinib. All patients but 1 had achieved a molecular response before stopping treatment; the only patient who never achieved a molecular response prior to discontinuing the TKI had a rapid relapse (1 month). At the last follow-up, 9 cases were still in treatment-free remission (TFR), whereas 5 eventually relapsed after 1, 1, 4, 14 and 30 months, respectively. Re-challenge with a TKI led to a hematological and molecular response in 3 of the 5 patients. The remaining 2 patients, who had been previously heavily treated and whose TFR was of only 1 month, received salvage standard chemotherapy but eventually died from ALL progression. The median time of TFR for the entire cohort of 14 patients was 20.5 months (1-82). When considering only the 9 patients who remain off treatment, the median time of TFR was 29.5 months (7-82) (Table 1, Figure 1).
Conclusions. We report the outcome of 14 Ph+ ALL patients who discontinued TKI treatment due to various reasons. Nine of them are still on TFR after more than 2 years at the last follow-up, reinforcing the concept that a TFR is feasible in selected adult Ph+ ALL patients. Of further relevance, TKI re-challenge was successful in 3/5 patients who relapsed, similarly to what observed in CML.
Disclosures: Cerrano: Insight Novartis Servier Abbvie Janssen Jazz Astellas Italfarmaco: Honoraria. Mulè: Astellas: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; ABBVIE: Honoraria. Papayannidis: Abbvie, Astellas, Servier, Menarini/Stemline, BMS, Pfizer, Amgen, Janssen, Incyte, Novartis: Honoraria; Pfizer, Astellas, Janssen, GSK, Blueprint, Jazz Pharmaceuticals, Abbvie, Novartis, Delbert Laboratoires: Membership on an entity's Board of Directors or advisory committees. Abruzzese: Takeda: Consultancy; Pfizer: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees. Fracchiolla: Abbvie, Jazz, Pfizer, Amgen: Speakers Bureau; Abbvie, Jazz, Pfizer, Amgen: Other: travel grants. Chiaretti: Gilead: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees.
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