Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S334 CML-250 The Prognostic Factors of Late Molecular Relapses after Treatment Discontinuation in Patients With Chronic Myeloid Leukemia Anna Petrova MD, PhD, Oleg Shukhov MD, PhD, Ekaterina Chelysheva MD, PhD, Margarita Gurianova MD, Irina Nemchenko MD, PhD, Anastasiya Bykova MD, PhD, Elena Kuzmina MD, Alina Kokhno MD, PhD, Hunan Julhakyan MD, PhD, Anna Turkina MD, PhD National Medical Research Center for Hematology, Moscow, Russian Federation Background: The search for simple and practical predictors of late molecular relapses (LMR) in patients (pts) with CML after tyrosine kinase inhibitors (TKIs) treatment discontinuation is an important goal for a wider implementation of observation in treatment-free remission (TFR) in clinical practice. Aims: To analyze the prognostic factors (PF) for LMR after TKIs discontinuation in CML pts in RUSKI study. Methods: Ninety-eight CML patients with TKI therapy duration ≥ 3 years and deep molecular response (DMR, BCR::ABL1≤ 0.01% IS) duration ≥ 2 years were included in prospective study RU-SKI. Molecular relapse and TKIs restart was in a case of major MR (MMR, BCR::ABL1>0.1%) loss. We considered the loss of MMR more than 6 months (mo) after treatment discontinuation as LMR and used 6-months landmark for LMR analysis. Results: Median (Me) time of follow-up without therapy was 55 mo (8-78 mo). Fifty-six (57%) out of 98 pts remained in TFR during first 6 mo after treatment discontinuation and were included in analysis. Subsequent loss of MMR was in 8 (14%) pts within a period of 8 to 47 mo after TKI discontinuation. Survival without MMR loss was 92% (CI 86-99%), 89% (CI 81-97%) and 84% (CI 73-94%) at 12, 36 and 60 mo after 6-months landmark respectively. We have found no differences (P=0.317) in LMR probability in pts groups with undetectable BCR::ABL1 (n=23, MR5) and detectable BCR::ABL1 level (n=33) during the first 6 mo after TKI stop. We assessed the probability of LMR depending on the maximum BCR::ABL1 level during the 6 mo after treatment discontinuation. We united pts with MR4, MR4.5, MR5 into 1 group (MR≥4, n=44) and compared with the pts group with MR4 loss (n=12). We confirmed the association between MR4 loss during the first 6 months and LMR development: the probability of LMR was 50% in the pts with MR3 versus 7% in pts with MR≥4 (P<0.0001). Conclusion: Only 14% patients, who maintained TFR during the first 6 months after treatment discontinuation, experienced LMR. Loss of MR4 in the first 6 months after TKI stop was the determining PF for the LMR probability. Keywords: chronic myeloid leukemia, prognostic factors, late molecular relapses CML-254 Asciminib Management in Chronic Myeloid Leukemia (CML) Patients With T315I Mutation Elena Kuzmina MD1, Elza Lomaia MD, PhD2, Elena Morozova MD, PhD3, Ekaterina Chelysheva MD, PhD1, Oleg Shukhov MD, PhD1, Anna Petrova MD, PhD1, Tamara Chitanava MD2, Yulia Vlasova MD3, Evgenia Sbityakova MD2, Tayana Makarova MD2, Irina Nemchenko MD, PhD1, Anastasiya Bykova MD, PhD1, Margarita Gurianova MD1, Hunan Julhakyan MD, PhD1, Alina Kokhno MD, PhD1, Anna Turkina MD, PhD1 1National Medical Research Center for Hematology, Moscow, Russian Federation. 2Almazov National Medical Research Centre, Moscow, Russian Federation. 3Raisa Gorbacheva Memorial Research Institute of Children’s Oncology, Moscow, Russian Federation Context: Asciminib is an allosteric tyrosine kinase inhibitor (TKI) that showed efficacy and a good safety profile in resistant CML patients, including those with T315I mutations. Objective: To show updated results of asciminib use in T315I-positive CML patients in 3 Russian centers within the Managed Access Program. Methods: Data from 24 T315I-positive CML patients in a 200 mg BID dose group were analyzed. Complete cytogenetic response (CCyR), major molecular remission (MMR), and deep molecular response (MR4) were assessed by cumulative incident function (CIF) with Gray’s test for comparison responses in subgroups. Survival analysis was performed by the Kaplan-Meier method. Patients: All patients were adults with Ph-positive CML in CP with a history of AP/BC. The median age was 49 (range 32-71), and 63% were female. Median CML duration before asciminib was 6.9 years (range 1-34). In patients who received ≥ 2 prior TKIs, 45% had ≥ 4 TKIs. The median follow-up was 21 months (range 6-39), and 5 (21%) patients discontinued asciminib (4 due to resistance, 1 due to a physician’s decision). Results: CIF of CCyR, MMR, and MR4 at 24 months was 57%, 57%, and 34%, respectively. Thirteen (54%) patients were ponatinib-pretreated. CIF of MMR in ponatinib-naive patients was higher compared to ponatinib-pretreated ones (90% vs 25% [P=0.001]). Four patients lost CCyR or MMR. Two-year overall survival at 24 months was 100%. The survival rate without treatment discontinuation was 75%. Six (25%) of 24 patients had additional chromosomal abnormalities before asciminib, and 4 achieved MMR. Seven patients had a history of non-T315I BCR::ABL1 mutations, and 5 achieved MMR/MR4. Thirteen (54%) patients experienced AEs of any grade, and 4 (17%) had AEs of grade 3 (neutropenia, hypercholesterinemia). No patients discontinued treatment due to toxicity. Conclusion: Asciminib is effective in highly pre-treated CML-CP patients with T315I mutations and other genetic events, though some are still challenging for clinicians. The results were significantly better in patients without resistance to ponatinib. A 200 mg BID dose safety profile was favorable, with no evidence of severe toxicity. Overcoming the resistance by adding other therapy should be investigated. Keywords: CML, T315I mutation, asciminib
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