AW-01. Gemtuzumab ozogamicin with FLAG regimen in refractory and relapsed AML patients: safety and efficacy
Bella I. Ayubova1, Sergey N. Bondarenko1, Ivan S. Moiseev1, Olga S. Uspenskaya2, Elena V. Karyagina3, Elena N. Misyurina4,
Evgenia I. Zhelnova4, Anna G. Smirnova1, Elena V. Babenko1, Ildar M. Barkhatov1, Tatyana L. Gindina1, Alexander D. Kulagin1,
1 RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov University, St. Petersburg, Russia
2 Leningrad Regional Clinical Hospital, St. Petersburg, Russia
3 City Hospital No.15, St. Petersburg, Russia
4 City Clinical Hospital No.52, Moscow, Russia
Dr. Saniya A. Abdrakhmanova, e-mail: A.email@example.com
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) gives really chance to prolong the duration of remission in the patients (pts) with refractory or relapsed AML (RR AML). The remission rate in RR AML does not achieve more than 10% and finding new therapeutic options is so important for such pts. Chemotherapy with high dose of cytarabine and purine analogues increases the remission rate up to 65%. Introduction of targeted drugs is the most promising strategy in the modern therapy of hematological malignancies. Gemtuzumab ozogamicin* (GO) is a recombinant, humanized anti-CD33 monoclonal antibody covalently attached to the cytotoxic antitumor antibiotic calicheamicin. The aim of the study is to analyze of safety and efficacy “GO-FLAG” regimen in adult patients with RR AML.
Patients and methods
The study included 46 pts with median age 34 (18-61) years. 15/46 (33%) pts developed primary refractory AML (RefAML); 31/46 (67%) pts had relapsed AML (RelAML). Based on the ELN 2017 classification, the prognosis was favorable for 14/46 (30%), intermediate, for 12/46 (26%), and adverse, for 20/46 (44%). All the pts treated by the combination of fractionated GO with regimen FLAG – “GO-FLAG”.
The follow-up was from 1 to 26 months (median 6.4 months). Overall survival and disease-free survival at 2 years (OS2 and DFS2) censored by allo-HSCT were 61% (95% CI 46-74) and 68% (95% CI 51-81), respectively. OS levels significantly correlated with ELN prognostic score, with a lower OS in adverse risk group (HR 3.7; 95%CI 1.4-9.7; p=0.028). The overall response rate (OR) was 34/46, (74%), at 95% CI 60-84: complete remission was achieved in 62% (21/34), remission with incomplete hematologic recovery, in 38% (13/34 cases). Higher response rate was noted in RelAML (RefAML, 56.3% vs RelAML, 83.3%, р=0.046). High OR rate was found in pts with extramedullary disease (92%, 12/13), at 95% CI 67-99, p=0.4). Allo-HSCT was performed after GO-FLAG in 20 (44%) pts (4, related, 6, unrelated, 10, haplo-HSCT). The median time from OR after GO-FLAG to HSCT was 61 (36-148) days. In all cases we observed grade 4 neutropenia, and thrombocytopenia (grade 4). Severe hemorrhagic complication (subdural hematoma) was registered in 1 pt (2.2%) at 95% CI 0.4-11. Sepsis was diagnosed in 14/46 cases, 30% (95% CI 19-45); fungal infections were revealed in 5/46 (11%), at 95% CI 5-23. Hepatotoxicity was presented as a transient increase in ALT level (<10ULN) in 5/46 (11%), at 95% CI 5-23. Sinusoidal obstruction syndrome did not occur in any of the pts. Early mortality was 9% (4/46 pts), at 95% CI 3-20. Immediate causes of death were leukemia progression (1 case), infectious complications (3 pts).
GO-FLAG demonstrated the efficacy and acceptable toxicity in pts with RR AML and can be used as a bridge therapy to allo-HSCT.
* GO was provided under program of extended access for vital indications.
Acute myeloid leukemia, target therapy, gemtuzumab ozogamicin.