P764 response and survival outcomes with hypomethylating agents in an argentinean cohort of 113 patients with chronic myelomonocitic leukemia

Abstract

Póster : Background: Hypomethylating agents (HMA) are the first line option for high-risk patient and lower-risk patient with transfusion dependence, or according to worsening clinical features. Data regarding HMA efficacy in CMML has been largely retrospective, or from MDS studies that included CMML patients, with overall response rates (ORR) ranging from 40% to 50% and true CR rates being <20%. Local data is scarce.

Aims: To examine the influence of prognostic factors at diagnosis and during the follow-up in the outcome and response to HMA therapy in a CMML cohort from Argentine.

Methods: We performed a retrospective analysis of 113 CMML patients from the Argentine Registry of MDS promoted by the Argentine Society of Hematology who were treated between January-07/February-22. Statistical analysis included Kaplan-Meier survival analysis, Cox proportional hazard and Chi2/Fisher’s exact test.

Results: The median age at diagnosis was 67 years (IQR 58-74) being 71.7% >60 years old, 18.8% a Charlson’s Index (CCI)>2, 81 (72%) were males, and 59 (52%) CMML-0, 25 (22%) CMML-1 and 29 (26%) CMML-2. At treatment initiation, 70.5% showed hemoglobin <10g/dL, 22.1% platelet counts <30,000/µL, 13.1% poor karyotypes and 91.2% at high risk according to the CPSS, IPSS, IPSS-R or Bournemouth scoring systems. During the follow-up, median 20 months (IQR 8.6-42.7), 45.1% evolve to AML and 75.2% died. Regarding HMA therapy, the median time to treat was 2.4 months, 78.8% patients received AZA and 22.2% DAC, the median number of cycles of 7 (IQR 4-12) during a median period of 8.1 months (m). The median overall survival (OS) of the cohort was 25.5m (95%CI 18.9-32.1), since treatment initiation 17.1m (95%CI 13.3-20.8), and after cessation 5.3m (95%CI 4.3-6.3).

Most of parameters and scoring systems analyzed were useful to predict outcome from diagnosis or from treatment initiation to last follow up. Cox regression analysis revealed that CCI>2 (HR 2.7, 95%CI 1.5-5.0, p=0.001), WHO classification (ref. CMML-0, CMML-1, HR 2.1, 95%CI 1.1-4.1, p=0.026; CMML-2, HR 3.4, 95%CI 1.6-6.8, p=0.001), lower hemoglobin level (<10g/dL, HR 1.9, 95%CI 1.1-3.5, p=0.023), platelet count <30.000/µL (HR 3.5, 95%CI 2.0-6.0, p<0.001), time to treat <6m (HR 4.7, 95%CI 2.4-9.1, p<0.001) and the presence of blast in PB (HR 1.7, 95%CI 1.0-2.8, p=0.05) and were independently associated with a reduced OS. Almost all parameters, with the exception of lower Hb levels, sustained their independency since treatment initiation.

A total of 99 patients were evaluated for response to treatment with an overall response rate (at 4-6 cycles) of 59.6% (CR/mCR/PR: 36.4%, HI: 23.2%, SD: 14.1%). The median overall survival of responders was 44.8m, similar to those with SD (33.2m, p=0.246), afterward grouped, with 8.3m in non-responders (p<0.001). We also evaluated whether prognostic factors were useful to predict response. Only the WHO 2016 proposal (CMML-0 61.6% vs 34.6%, CMML-1 21.9% vs 30.8%, CMML-2 16.4 vs 34.6%, p=0.046) and the absence of peripheral blasts (61.1% vs 36.0%, p=0.037) were associated with statistically different rates of response, with a tendency to treat later ≥6m (37.0% vs 15.4%, p=0.05).

Summary/Conclusion: The present series represents the first experience in Latin America evaluating HMA agents in CMML patients. Our results highlight the adverse impact of several parameters, including the severity of the thrombocytopenia <30,000/µL on the outcome of CMML patients under HMA. However, clinical parameters are limited to predict the response rate.