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Couturier, M.-A.1; Thomas, X.2; Raffoux, E.3; Huguet, F.4; Berthon, C.5; Simand, C.6; Gallego-Hernanz, M.-P.7; Hicheri, Y.8; Hunault-Berger, M.9; Saillard, C.10; Leguay, T.11; Chevallier, P.12

doi: 10.1097/01.HS9.0000562056.77454.d3
Poster Session II: Acute lymphoblastic leukemia - Clinical

1Hematology, Hôpital MORVAN, CHRU BREST, BREST

2Hematology, Hôpital Lyon-Sud, LYON

3Hematology, APHP Saint-Louis, PARIS

4Hematology, Institut Universitaire de Cancer Toulouse - Oncopole, TOULOUSE

5Hematology, Hôpital Claude Huriez, CHRU Lille, LILLE

6Hematology, CHU de Hautepierre, Strasbourg, STRASBOURG

7Hematology, CHU La Miletrie, Poitiers, POITIERS

8Hematology, Hôpital Saint Eloi, CHRU Montpellier, MONTPELLIER

9Hematology, CHRU Angers, ANGERS

10Hematology, Institut Paoli Calmettes, Marseille, MARSEILLE

11Hematology, Hôpital Haut-Leveque, CHU Bordeaux, BORDEAUX

12Hematology, Hotel Dieu, CHU Nantes, NANTES, France

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Despite the progress achieved with the combination of BCR-ABL1 tyrosine kinase inhibitors (TKI) and chemotherapy, the prognosis of patients with a refractory/relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1+ ALL) is still very dismal. However, new drugs have recently improved outcomes of these patients: ponatinib has shown some efficacy in this context and a recent study has reported very encouraging results of the anti-CD3/CD19 monoclonal antibody blinatumomab as single-agent. Data regarding the efficacy and tolerance of a combination of blinatumomab+ponatinib (blina/pona) are still scarce.


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This was a retrospective study in 12 French centers: 23 patients with a relapsed/refractory Ph1+ ALL have concomitantly received blinatumomab (28 mg/day by continuous infusion for 28 days every 6 weeks) and daily orally ponatinib.

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There were 13 males and 10 females, with a median age of 58 years (range:17-72). All patients, but 3 with blast crisis of chronic myeloid leukemia, had de novo Ph1+ ALL. Seven cases (30.4%) had BCR-ABL1 T315I mutation. Patients received the blina/pona combination, either after a first (n = 10) or a second or more (n = 11) cytologic relapse. There was one refractory patient. One patient received blina/pona in consolidation, after serious side effects from front-line chemotherapy. Previous allograft and autograft has been performed in 9 and 4 patients, respectively. The majority of patients (n = 15) had previously received 3 2 or more lines of TKI. The median number of blinatumomab cycle administered per patient was 3 (range: 1-5) while ponatinib was administered continuously at an initial dose of 45 mg once daily in 17 pts (74%) and 30 mg in 6 pts (26%) during a median time of 5 months (range: 1-41) from first blinatumomab cycle. The toxicity profile was safe: blinatumomab was stopped in 48% of cases because of neurologic events in 4, infections in 4 and cytokine release syndrome in 3 patients; ponatinib was stopped in 22% of cases because of neurologic events in 3, hepatobiliary disorder in 1 and severe arteriopathy in 1 patient who had others vascular disease risk factors. All neurologic events resolved after stopping involved drug. All but one patient (95.6%) obtained a cytologic complete remission (CR), of whom 19/22 (86%) achieved a complete molecular response (CMR). However, 2 patients were documented with CNS relapse, treated with intrathecal infusion of chemotherapy. Then, 7 patients underwent allogeneic transplant (including 3 patients already allotransplanted before blina/pona). With a median follow-up of 29 months (range: 17.5-66.7) for the alive patients (74%), median overall survival from first cycle of blina/pona was not reached and leukemia-free survival was 18.2 months (range: 1.3-41). At last follow-up (February 2019), 7 relapses had occurred at a median of 7 months (range: 1.3-41) from first blina/pona cycle and 1 patient had refractory disease. 6 patients (26%) had died of 2 bacterial infections, 2 fungal infections, 1 secondary cancer and 1 progressive refractory ALL. Among the 17 patients alive, one had relapsed and 16 are still in CMR, but 2 with CNS relapse. Twelve patients are still under ponatinib medication.

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The combination of blinatumomab+ponatinib appears effective and tolerable in relapsed Ph1+ALL patients. It could replace chemotherapy salvage regimens and allow a brigde to allogeneic transplantation, or may be tested in first-line therapy in the future. Our results have to be confirmed prospectively on a larger cohort of patients.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.