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876 Retrospective Analysis of the Outcomes of Patients with Relapsed/Refractory Acute Myeloid Leukemia Included in a Patient Named Program of Gemtuzumab OzogamicinClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 615. Acute Myeloid Leukemias: Commercially Available Therapies, Excluding Transplantation and Cellular Immunotherapies: Updates in treatment for high-risk AML
Hematology Disease Topics & Pathways:
Biological, Adults, AML, Non-Biological, Clinical Research, Chemotherapy, Diseases, Real World Evidence, Therapies, Myeloid Malignancies, Monoclonal Antibody Therapy, Study Population
Monday, December 13, 2021: 7:30 PM

Juliette Lambert1*, Pierre Peterlin2*, Cecile Pautas, MD3*, Emmanuel Raffoux, MD4*, Denis Caillot, MD5,6*, Ollivier Legrand, MD, PhD7*, Magalie Joris, MD8*, Anna Berceanu, MD9*, Jean Valere Malfuson, MD, PhD10*, Sylvain Chantepie, MD11*, Marc Bernard, MD12*, Lauris Gastaud, MD13*, Arnaud Pigneux, MD, PhD14*, Omar Benbrahim, MD15*, Caroline Bonmati, MD16*, Hunault-Berger Mathilde, MD, PhD17*, Hervé Dombret, MD, PhD18, Philippe Rousselot19*, Sylvie Chevret, MD, PhD20* and Sylvie Castaigne, MD1*

1Hematology Department, Versailles Hospital, Le Chesnay, France
2Clinical Hematology, Nantes University Hospital, Nantes, France
3Hematology Department, Henri Mondor University Hospital, CRETEIL, France
4Université de Paris, Hematology department, Saint-Louis hospital, APHP, Paris, France
5Hematology Department, Le Bocage University Hospital, Dijon, France
6Hematology Department, Dijon University Hospital, Dijon, France
7Department of Clinical Hematology and Cellular Therapy, Saint Antoine Hospital, Assistance Publique - Hôpitaux de Paris, Sorbonne Université, Paris, France
8Hematology department, CHU Amiens, Amiens, France
9Department of Clinical Hematology, Besançon University Hospital, Besançon, France
10Hematology Department, Percy Hospital, Clamart, France
11Hematology Department, Caen University Hospital, Caen, France
12Hematology Department, Rennes University Hospital, Rennes, France
13Medical Oncology Department, Antoine Lacassagne Hospital, Nice, France
14Hematology Department, Bordeaux University Hospital, Pessac, France
15Hematology Department, Orleans CHR, Orleans, France
16Hematology Department, Nancy University Hospital, Vandoeuvre Lès Nancy, France
17Hematology Department, Angers University Hospital, Angers, France
18Saint-Louis University Hospital, Paris, France
19Hematology Department, Centre Hospitalier de Versailles, LE CHESNAY CEDEX, France
20APHP, Saint-Louis University Hospital, Department of Biostatistics, PARIS, France

Introduction: In 2010 the French Health Agency opened a compassionate patient named program of gemtuzumab ozogamicin (GO, Mylotarg®) in relapsed/refractory (R/R) patients with acute myeloid leukemia (AML). Of note, since 2012, it was recommended to use GO at the dose of 3 or 6 mg/m2 in addition to chemotherapy. We conducted a retrospective trial (NCT03287128) to evaluate the efficacy and the safety of GO-based regimen in R/R adult AML patients.

Patients and methods: We retrospectively collected data of patients older than 18 years treated with GO-based regimen for AML in first relapse or for refractory AML, defined by failure after a prior standard intensive chemotherapy, in 18 French centers between December 15, 2011 and November 10, 2016. The primary objective was to assess the response to GO-based regimen. Patients were considered in response if reaching complete remission (CR), CR without platelet recovery (CRp) or CR with incomplete hematological recovery (CRi). Secondary objectives were the cumulative incidence of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the safety of the use of GO-based regimen.

Results: Three hundred and thirty-five adult patients with R/R AML were included. Median age was 58 years (20 to 80 years). At diagnosis, cytogenetics was favorable in 50 (17%) patients, intermediate in 173 (59%) and adverse in 60 (20%). ELN distribution was favorable: 35%, intermediate: 42% and unfavorable: 23%. NPM1 mutation was present in 29% of patients and FLT3 mutation in 23%. Most patients had de novo AML (84%). Two hundred and thirty-eight patients (79%) were in first relapse and 65 (21%) had a refractory AML. The time between first diagnosis of AML and treatment with GO-based regimen was 4 to 16 months (median 9.4 months). Most patients (88%) received GO in combination with various intensive chemotherapy scheme including “7+3” with anthracycline/cytarabine (n=39 patients), intermediate and high-dose cytarabine (n=68), cytarabine in continuous intravenous infusion (n=78), mitoxantrone/cytarabine (n=49) and fludarabine/cytarabine and/or amsacrine and/or etoposide chemotherapy (n=35). Median follow-up time was 11 months.

Among the 305 patients, 191 responded to GO-based regimen: 110 (36%) were in CR, 62 (20%) were in CRp and 19 (6%) in CRi for an overall response rate (CR+CRp+CRi, ORR) of 63%. In multivariate analysis, response was associated with age <50 years, de novo AML and relapse status. Among the 191 responders, 110 received additional courses of chemotherapy, 69 with GO. Main reason to not receive additional course (with or without GO) was allo-HSCT project. In the whole population, median overall survival (OS) after day 1 of treatment with GO was 11.2 months. In the population of responders, median OS after response was 20.4 months. In multivariate analysis, longer survival was associated with age < 50 years, de novo AML and favorable ELN group. Cumulative incidence of relapse at 24 months after response was 46%. One hundred and forty-seven patients received allo-HSCT, including 122 responders after GO-based regimen and 25 patients in treatment failure. Cumulative incidence of allo-HSCT at 18 months was 48%. Four-year OS was 48% in transplanted patients versus 19% in non-transplanted patients (Figure 1).

Regarding safety of GO-based regimen, early deaths occurred within <30 days after the first dose of GO in 14 patients, and within <60 days in 35 patients. Myelosuppression was observed in all patients. Mean duration of thrombocytopenia <100 G/L was 35 days in responders. Bleeding grade 3 or more was observed in 22 patients (7%). Infection grade 3 or more was observed in 112 patients (30%). Sinusoidal obstruction syndrome (SOS) after GO treatment was reported in 6 patients, resolving in 4 of them. Four cases of fatal SOS were reported after allo-HSCT. Toxic deaths, i.e., not related to worsening leukemia, were reported in 20 patients after the first course of chemotherapy, 3 after additional courses and 33 after allo-HSCT.

Conclusion. Our study is the first to report efficacy data in the real-world setting of R/R AML adult patients treated with GO-based regimen. In our cohort of 305 patients, response rate was 63% and GO-based regimen appears as a valuable bridge-to-transplant option. Safety analysis showed toxicities consistent with the known safety profile of GO and chemotherapy.

Disclosures: Lambert: CELGENE/BMS: Consultancy; ASTELLAS: Consultancy; PFIZER: Speakers Bureau. Pautas: PFIZER: Consultancy; ABBVIE: Consultancy. Raffoux: ASTELLAS: Consultancy; PFIZER: Consultancy; ABBVIE: Consultancy; CELGENE/BMS: Consultancy. Legrand: Servier: Consultancy. Gastaud: PFIZER: Consultancy; CELGENE/BMS: Consultancy; ABBVIE: Consultancy; GSK: Consultancy. Pigneux: Amgen: Consultancy; Sunesis: Consultancy, Research Funding; BMS Celgene: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Mathilde: SERVIER: Consultancy; ABBVIE: Consultancy. Dombret: Amgen: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; Novartis: Research Funding; Pfizer: Honoraria, Research Funding; Servier: Research Funding; Abbvie: Honoraria; BMS-Celgene: Honoraria; Daiichi Sankyo: Honoraria. Rousselot: Incyte, Pfizer: Consultancy, Research Funding. Castaigne: PFIZER: Consultancy.

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