BLINATUMOMAB + PONATINIB FOR RELAPSED PH1-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA: THE FRENCH EXPERIENCE.
Author(s): ,
Marie-Anne Couturier
Affiliations:
Hematology,Hôpital MORVAN, CHRU BREST,BREST,France
,
Xavier Thomas
Affiliations:
Hematology,Hôpital Lyon-Sud,LYON,France
,
Emmanuel Raffoux
Affiliations:
Hematology,APHP Saint-Louis,PARIS,France
,
Françoise Huguet
Affiliations:
Hematology,Institut Universitaire de Cancer Toulouse - Oncopole,TOULOUSE,France
,
Céline Berthon
Affiliations:
Hematology,Hôpital Claude Huriez, CHRU Lille,LILLE,France
,
Célestine Simand
Affiliations:
Hematology,CHU de Hautepierre, Strasbourg,STRASBOURG,France
,
Maria-Pilar Gallego-Hernanz
Affiliations:
Hematology,CHU La Miletrie, Poitiers,POITIERS,France
,
Yosr Hicheri
Affiliations:
Hematology,Hôpital Saint Eloi, CHRU Montpellier,MONTPELLIER,France
,
Mathilde Hunault-Berger
Affiliations:
Hematology,CHRU Angers,ANGERS,France
,
Colombe Saillard
Affiliations:
Hematology,Institut Paoli Calmettes, Marseille,MARSEILLE,France
,
Thibaut Leguay
Affiliations:
Hematology,Hôpital Haut-Leveque, CHU Bordeaux,BORDEAUX,France
Patrice Chevallier
Affiliations:
Hematology,Hotel Dieu, CHU Nantes,NANTES,France
EHA Library. COUTURIER M. Jun 15, 2019; 267247; PS946
Dr. Marie-Anne COUTURIER
Dr. Marie-Anne COUTURIER
Contributions
Abstract

Abstract: PS946

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
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.

Aims
 

Methods

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.

Results

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.

Conclusion
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.

Session topic: 2. Acute lymphoblastic leukemia - Clinical

Keyword(s): Relapsed acute lymphoblastic leukemia, Tyrosine kinase inhibitor

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