-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

4957 A Phase 2 Study of Ponatinib for Prevention of Relapse after Allotransplantation in FLT3-ITD + AML Patients : The Ponallo TrialClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 723. Allogeneic Transplantation: Long-term Follow-up and Disease Recurrence: Poster III
Hematology Disease Topics & Pathways:
Acute Myeloid Malignancies, AML, Diseases, Therapies, therapy sequence, Adverse Events, Myeloid Malignancies, Technology and Procedures, Pathology
Monday, December 11, 2023, 6:00 PM-8:00 PM

Patrice Chevallier, MD1, Anne Thiebaut, MD2*, Sylvie François, MD3*, Sylvain Chantepie, MD4*, Marie Thérèse Rubio, MD, PhD5*, Hélène Labussière-Wallet6*, Eolia Brissot7*, Natacha Maillard, MD8*, Anne Huynh, MD9*, Valerie Coiteux, MD10*, Alice Garnier, MD11*, Amandine Le Bourgeois12*, Pierre Peterlin1* and Thierry Guillaume, MD, PhD12*

1Nantes University Hospital, Nantes, France
2service d'hématologie clinique, CHUGA Grenoble, Grenoble, France
3Maladies du sang, CHU Angers, Angers, France
4Institut d'Hématologie, CHU de Caen, Caen, France
5Nancy University Hospital, Vandoeuvre Les Nancy, FRA
6Centre Hospitalier Lyon Sud, Lyon, France
7Sorbonne Université Service d' Hématologie Clinique et Thérapie Cellulaire, Hospital Saint-Antoine, Centre de Recherche Saint-Antoine (CRSA), Paris, France
8Hematology Department, CHU de Poitiers, Poitiers, France
9Institut Universitaire du Cancer Toulouse - Oncopole, Toulouse, France
10Hematology department, Centre Hospitalier Universitaire, Lille, France
11Hematology clinic, Nantes University Hospital, Nantes, France
12Nantes University Hospital, Nantes, FRA

Background : For acute myeloid leukemia (AML) patients relapse remains a major issue after allogeneic stem cell transplantation (allo-SCT). In those with a FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD+), survivals have been improved with the use of small molecule Flt3 receptor protein-tyrosine kinase inhibitors in maintenance due to a significant decrease of relapse after allo-SCT. Ponatinib (pona) is a multikinase inhibitor that is approved for the treatment of Philadelphia chromosome-positive acute lymphoblastic and chronic myelogenous leukemias. It has also activity against FLT3-mutants including ITD and ITD691L but not D835 within the Flt3 activation segment. Pona may then represent an alternative drug for maintenance after allo-SCT in FLT3-ITD+ AML patients.

Methods : This was a multicenter phase 2 non-randomized prospective study testing the efficacy and tolerability of pona after allo-SCT in FLT3-ITD+ AML patients (ClinicalTrial.gov ID : NCT03690115). The main objective was the incidence of relapse at 2 years post-transplant with the hypothesis that this incidence at 2 years will be reduced at 15% instead of 30%. Seventy-seven patients had to be included. Inclusion criteria were all patients, aged between 18 and 70 yo, with a FLT-3 ITD+ AML in cytologic complete remission (<5% of bone marrow blasts) and a documented engraftment at the time of starting pona after an allo-SCT using any type of conditioning regimen and donor. The control of a GVHD (if present) was mandatory as well as a platelets count ≥70 Giga/l and a neutrophils count ≥ 1 Giga/l at time of inclusion. The study was supported by Incyte.

Initially, pona administration had to start between day +60 and +90/100 at the dose of 30 mg/day for 1-year. However, because of excesssive hematopoietic toxicity, an amendment was made after the 14th patient to start pona between day 100 and day 120 post-allo. During the study, It was allowed to restart pona at 15 mg/day after resolution of 30 mg dose related toxicities. After 1 year of pona it was not allowed to start a new FLT3 inhibitor or pursue pona.

Results : Twenty-three patients were included between December 2019 and April 2022. Among them, 22 were effectively treated. Indeed, the last patient included did not receive pona due to hepatic abnormalities incompatible with the start of pona. Also, because of a very low rate of enrollment, the trial was closed prematurely in accordance with the sponsor in December 2022. Results for the 22 treated patients are reported here. Patient characteristics are given in Table 1. With a median follow-up of 740 days (range : 374-930), 1-y and 2-y overall survival were 81.3% (66.3-99.6) and 63.9% (45.4-90.0), and 1-y and 2-y leukemia-free survival were 54.5% (37.2-79.8) and 49% (31.8-75.7), respectively. Ten relapses occured at a median of 186 days (range=69-481) after allo-SCT with a CI of relapse of 45.5% at 2 years.

Pona was started at a median of 69 days post-allo-SCT (range : 60-130). The median duration of treatment was 75.5 days (range : 4-369). Only 3 patients received one year of treatment and all at 30 mg/day as required by the protocol. The reasons for stopping pona were toxicity in 11 patients, relapse in 6, toxicity then relapse in 1, GVHD then relapse in 1. Among the 13 patients who stopped pona for toxicity or GVHD, 6 restarted pona (15 mg n=5, 30 mg n=1) then stoppped again for toxicity (n=4) or progression (n=2).

A total of 36 adverse events related to pona were documented in 17 patients. The majority was grade 1 or 2 (n=27, 75%) while 6 grade 3 (17%) and 3 grade 4 (8%) occured. (Table 2)

Conclusion : Ponatinib administration after allo-SCT is associated with toxicity and do not reduce relapse or improve survival in this small cohort of FLT3+ AML patients. Other FLT3 inhibitors have to be considered in FLT3+ AML patients for maintenance after allo-SCT.

Disclosures: Chevallier: Takeda: Honoraria; Incyte: Honoraria, Research Funding; Immedica Pharma: Honoraria; Mallinckrodt Pharmaceuticals: Honoraria; Sanofi: Honoraria; Servier: Honoraria. Huynh: Medac: Other: Advisory board; Servier: Other: Advisory board; Astellas: Other: Advisory board; Jazz: Other: travel fees, advisory board; Pfizer: Other: advisory board; Neovii: Other: Advisory board; Novartis: Other: travel fees, advisory board. Coiteux: Incyte Biosciences: Honoraria, Speakers Bureau; Pfizer: Honoraria; Novartis: Honoraria.

OffLabel Disclosure: Ponatinib for prevention of relapse post-allograft

*signifies non-member of ASH