Gemtuzumab ozogamicin with chemotherapy "FLAG" in refractory and relapsed AML patients: safety and efficacy

[摘要] Allogeneic hematopoietic stem cell transplantation (allo-HSCT) gives chance for a potential cure in patients with refractory or relapsed (R/R) acute myeloid leukemia (AML). The current study evaluated of the outcomes of combination chemotherapy FLAG with gemtuzumab ozogamicin (GO) (GO-FLAG) in adult patients with R/R AML. The study included 48 patients with median age 34 (18-61) years. Primary refractory was in 16 (33%) and relapsed AML in 32 (67%) patients. Based on the 2017 ELN risk stratification by genetics the prognosis was favorable for 5 (10%) cases, intermediate for 20 (42%), and adverse – 23 (48%). Sixty-nine percent (33/48) of patients had only bone marrow involvement and 31% (15/48) had extramedullary disease. Overall response (OR) was 75% (CI95% 61-85%): complete remission was in 26 (52%) patients, remission with incomplete recovery – 10 (21%). Lowest response rate was observed in patients with unfavorable karyotype (AOR 0.11 (CI 95%: 0.02-0.7; p=0.02) and high disease burden (AOR 0.12 (CI 95%: 0.02-0.7; p=0.02). High response rate was observed in patients with extramedullary disease and was achieved in 87% (CI 95% 62-96). Allo-HSCT was performed in 52% of patients. The median time from OR to HSCT was 40 (16-224) days. Overall survival was (OS) 31.3% (CI 95% 20-45) with a median of 6.9 months (4.3-9.5 months). Two-year relapse-free survival (RFS2) was 27.8% (CI 95% 15.6-44), median RFS2 was 4.9 months (3.3-6.5 months). In the multivariate analysis, event-free survival (EFS) was significantly associated with successful bridging to allo-HSCT (HR=0.13; CI 95%: 0.04-0.4; p<0.001) and presence of late relapse (HR=0.095; CI 95%: 0.02-0.41; p=0.002). No unexpected toxicity was observed after GO-FLAG. Treatment-related early mortality was in 8%. The GO-FLAG chemotherapy in adult patients with R/R AML has demonstrated efficacy and acceptable toxicity and can be used as a bridge to allo-HSCT.

[学科分类] 肿瘤学

[关键词] Acute myeloid leukemia;target therapy;gemtuzumab ozogamicin;FLAG.