Pb1853: outcomes refractory/relapsed acute myeloid leukemia with extramedullary manifestations after gemtuzumab ozogamicin therapy

Topic: 4. Acute myeloid leukemia - Clinical Background: Extramedullary manifestations (EM) are rare event in acute myeloid leukemia (AML) and occur in 3 to 10% at the time of diagnosis. However, the rate of EM can be up to 30% at relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). EM in AML has been associated with increased risk of relapse and worse outcomes post-chemotherapy. Most commonly, EM are presented after different myeloid neoplasm. For this reason, therapy of this cohort is a challenge. Introduction of targeted drugs is the most promising strategy in the modern therapy of hematological malignancies. Aims: To evaluate the efficacy of gemtuzumab ozogamin therapy patients with R/R AML with EM Methods: The study included 30 patients with EM out of 150 adult patients with refractory/relapsed AML analyzed from 2017 to 2022. Median age was 34 (18-68) years. Primary refractory AML (PrRef) was diagnosed in 9 (30%) cases, relapsed AML (Rel) – 21 (70%). The first Rel had 14 (66.7%) pts and two or more Rel – 7 (33.3%). The early Rel was observed in 16 (76.2%) and late Rel were in 5 (23.8%) of cases. Rel after allo-HSCT was in 8 (26.7%) pts. Based on the ELN 2017 classification, the prognosis was favorable for 8 (26.3%), intermediate for 13 pts (43.3%), and adverse for 9 pts (30%). Isolated EM was observed in 7 (23.3%) and combination with bone marrow in 23 (76.7%) pts. Twelve pts (40%) was with acute myelomonocytic leukemia. All pts treated by the combination of fractionated GO with high doses chemotherapy (HDChT) and less intensive therapy (LIT), in 20 (66.7%) and 10 (33.3%), respectively (Tab. 1). Results: The overall response rate (ORR) was in 20 (66.7%) (95% CI 47.2-82.7): complete remission was achieved in 14 (46.7%), remission with incomplete hematologic recovery – 3 (10%), partial remission – 3 (10%). Age, sex, genetic group did not reveal statistically significant associations. High ORR was observed after GO with HDChT (80%) vs GO with LIT (40%), P=0.045. Allo-HSCT was performed after therapy in 9 (30%) pts (3- related, 3-unrelated, 3– gaplo). The median time from ORR to allo-HSCT was 64 (36-130) days. Overall survival (OS) was 36.7 (95% CI: 19.9 – 56.1) with median 5.9 months (95% CI: 3.2 – 16.4). From the patient who achieved ORR was evaluated disease-free survival (DFS): 35% (95% CI: 15.4 – 59.2), median DFS 5.1 months (95% CI: 2.8 – 19.1). According to multivariable analysis, the risk of any event (EFS) was decreased in pts with ORR (HR 0.17; CI95%: 0.06-0.47; p<0.001) (Fig. 1). In all cases we observed neutropenia of 4 gr. and thrombocytopenia 4 gr. Severe hemorrhagic complications was in 1 pts (3.3%). Sepsis/bloodstream infection was in 5 (16.6%). Hepatotoxicity was presented as a transient increase in ALT level (<10ULN) in 10% (95% CI 4-24). Sinusoidal obstruction syndrome did not occur in any of the patients. Early mortality was 6.7% (95% CI 1.9-21.3). Causes of death were infectious complications (1 pts) and hemorrhagic complications (1 pts). No direct association with the GO and death was observed. Summary/Conclusion: According to the literature, the main predictor for improving OS for AML patients with EM is achievement of ORR and subsequent allo-HSCT in ORR is comparable to the outcomes of OS of pts with AML without EM. Thus, the analysis of our study, which demonstrated high efficiency and acceptable toxicity immunochemotherapy - gemtuzumab ozogamicin in combination, gives a real chance to improve the outcomes of this cohort.Keywords: Acute myeloid leukemia, AML, relapsed/refractory