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• W4385856762 abstract "Topic: 4. Acute myeloid leukemia - Clinical Background: Extramedullary (EM) manifestations of acute myeloid leukemia (AML) are rare, but have a broad clinical spectrum. EM has traditionally been approached with conventional chemotherapy (CTX) and/or radiation. Recently, venetoclax (VEN) in combination with hypomethylating agents (HMA) or low-dose cytarabine was approved for treatment of newly diagnosed AML patients (pts) who are ≥ 75 years or who are ineligible for intensive CTX due to comorbidity. Whether EM AML responds to VEN/HMA is not known. Aims: To characterize adult pts with EM AML and evaluate outcome after VEN/HMA treatment within an international retrospective cohort analysis. Methods: We studied 41 pts (median age, 66 years; range, 19-81 years) treated with VEN/HMA between 2017 and 2022. Eighteen (44%) of 41 pts were relapsed or refractory after intensive CTX or allogeneic hematopoietic stem cell transplantation (allo-HCT; n=10/18) prior to VEN/HMA. Up to 31 VEN/HMA cycles (median, 2 cycles; ≤2 cycles, n=23; 3-4 cycles, n=10; ≥5 cycles, n=8) were administered according to the previously approved regimens. EM response assessment was performed by CT or PET-CT and bone marrow (BM) and/or cerebral fluid/MRI evaluation in case of central nervous system involvement. Results: Type of AML was de novo in 23 (56%), secondary after myelodysplastic syndrome/myeloproliferative neoplasm in 17 (41%), and therapy-related in 1 (3%) patient. Median white blood cell and platelet counts at time of EM presentation were 6.6/nl (range, 0.6-131.2/nl) and 66/nl (range, 6-307/nl), respectively. Fifteen pts (37%) were female; ECOG was ≤2 in all pts. Overall, pts had in median 2 EM manifestations (range, 1-5; Table 1). In addition to EM disease, n=34 (83%) pts had BM involvement. Cytogenetic analysis was performed in 38 (93%) pts. Seventeen (45%) pts showed a complex karyotype, 9 (24%) a normal karyotype and 12 (31%) pts other abnormalities. NPM1 was mutated in 8 (20%) and 3 (7%) pts had a FLT3-ITD mutation. TP53 and spliceosomal mutations could be detected in 11 (27%), each. Risk classification according to ELN 2022 was low-risk in 5 (12%), intermediate-risk in 13 (32%) and high-risk in 20 (49%) of the pts (missing, n=3; 7%). Eighteen (44%) pts achieved CR/CRi after VEN/HMA treatment, of whom 3 were heavily pretreated including allo-HCT. Five (12%) pts achieved a partial remission (PR) and 4 (10%) stable disease. The overall response rate (ORR; including CR/CRi/PR) was 56% (n=23). Six pts went on to allo-HCT (CR/CRi, n=4; PR, n=2). Prior to allo-HCT all pts received ≤4 cycles (2 cycles, n=3; 1/3/4 cycles, n=1, each). Conditioning was dose-reduced in 4 and myelo-ablative in 2 pts. Median follow-up was 28.8 months (95%-CI, 11.5 months - not reached) and median overall survival (OS) 6.4 months (95%-CI, 3.9-12 months). One-year and 2-years OS rates were 26.4% (95%-CI, 15-47%) and 14% (95%-CI, 5-36%), respectively. Age with a cut-off of 60 years had no impact on OS (P=0.80). Relapse occurred in 11 of 18 (61%) pts who had achieved CR/CRi after VEN/HMA treatment. Of those, all except than two succumbed of their disease. Five (28%) pts are in ongoing CR/CRi and 2 died in CR. All pts who did not respond died due to disease progression. Summary/Conclusion: In our group of pts with high-risk features, treatment with VEN/HMA resulted in an encouraging ORR of 56% with a CR/CRi rate of 44%. However, VEN/HMA alone may not be effective in maintaining disease control. Whether allo-HCT after disease control with VEN/HMA is a veritable option needs to be evaluated in the future.Keywords: Acute myeloid leukemia, Venetoclax, Clinical outcome" @default.
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• W4385856762 date "2023-08-01" @default.
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• W4385856762 title "PB1840: OUTCOME OF ADULT ACUTE MYELOID LEUKEMIA PATIENTS WITH EXTRAMEDULLARY DISEASE AFTER TREATMENT WITH VENETOCLAX/HYPOMETHYLATING AGENTS" @default.
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