PS1036 UPDATED RESULTS FROM A PHASE 1 STUDY OF GILTERITINIB IN COMBINATION WITH INDUCTION AND CONSOLIDATION CHEMOTHERAPY IN PATIENTS WITH NEWLY DIAGNOSED AML
Authors: K. Pratz, M. Cherry, J. Altman, B. Cooper, J.C. Cruz, J. Jurcic, M. Levis, T. Lin, A. Perl, N. Podoltsev, G. Schiller, C. Liu, E. Bahceci
Journal: HemaSphere (2019)

Background: The prognosis of patients with refractory/early relapsed acute myeloid leukemia (AML) remains poor. Between 10% and 40% of newly diagnosed patients are categorized as resistant to intensive induction therapy. Moreover, there are no current standard treatments in this situation. Significant improvements in survival are described in patients achieving complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) followed by allogeneic hematopoietic cell transplantation (allo-HCT). Recently, a combination of gemtuzumab ozogamicin (GO) with all-trans retinoic acid, high-dose cytarabine, and mitoxantrone (GO-A-HAM) was reported as a promising regimen compared to others in this clinical situation (Wattad et al. Leukemia 2017;31(6):1306–1313.). Aims: To assess gemtuzumab ozogamicine (GO)-based salvage therapy regimens with respect to response (CR/CRi), overall survival (OS) and survival after allo-HCT in adult patients with refractory/early relapsed AML. Methods: Patients (18 to 71 years) with refractory/relapsed AML in need of salvage therapy were accrued between 2007 and 2016 in three European countries. Salvage therapy consisted either of one cycle of fludarabine 30 mg/m2 days 1–4, idarubicin 10 mg/m2 days 1–3, high dose Ara-C (HDAC) 2 g/m2 days1–4 and GO 3 mg/m2 on day 1 (FLAGOIDA regimen) or HDAC 2 g/m2 on days 1–5, fludarabine 30 mg/m2 days 1–5 and GO 6 mg/m2 on day 6 (FLU-HDAC-GO regimen) or Ara-C ± etoposide ± fludarabine and GO 3 mg/m2 on day 1 (GO-Ara-C regimens). We compared the three therapy regimens in terms of response rate, OS, and OS after HCT and compared the results with the ones obtained in a published (Hütter-Krönke et al. Haematologica. 2016 Jul;101(7):839–45.) phase II study of the GO-A-HAM regimen (GO 3 mg/m2 on day 1, all-trans retinoic acid (45 mg/m2 orally on days 4–6, 15 mg/m2 orally on days 7–28, HDAC 3 g/m2 on days 1–3 and mitoxantrone 12 mg/m2 on days 2–3). Results: Overall, 81 patients receiving salvage therapy with GO were included into the study. The median age at inclusion was 53 years with significant heterogeneity between the cohorts (p = 0.04), 48% of the patients were male and 85% had de novo AML. Response (CR/CRi) to salvage therapy were 63% with FLAGOIDA, 41% with FLU-HDAC-GO and 58% with GO-Ara-C group. Response-rates achieved were not different between groups and in comparison with the GO-A-HAM regimen with 51% (p = 0.25). The only factor significantly associated with response in multivariable analysis was unfavorable genetic risk group according to ELN risk classification (OR: 0.48 p = 0.03). Overall 68% of the patients after salvage therapy with FLAGOIDA, 26% after FLU-HDAC-GO, and 50% after GO-Ara-C proceeded to allo-HCT, compared to 76% in the GO-A-HAM cohort. There was a significant difference with regard to OS between the different cohorts (p < 0.0001) with an OS of the total cohort of 28% after 3 years. However, when we focused on patients proceeding to an allo-HCT outcome was comparable between the different cohorts (p = 0.52) with 39% after 3 years. Summary/Conclusion: Data from our study on real-world compared to clinical-study data on GO in refractory AML-patients confirmed that GO-based salvage regimens are associated with a high response rate irrespective of the different chemotherapy regimens combined with GO. Furthermore, salvage therapy including GO followed by allo-HCT emerges as effective strategy in AML patients with refractory disease after standard induction therapy.