Outcomes of venetoclax‐based therapy in chronic phase and blast transformed chronic myelomonocytic leukemia

Hypomethylating agent and venetoclax in patients with chronic myelomonocytic leukemia: Is the combination indeed better?

“…Notably, CR rate with HMA‐Ven in all 3 cohorts of CMML ( n = 19, 6, and 13) to date has been <10%, substantially lower than patients with myelodysplastic syndrome and AML. Mutations in ASXL1 , TET2 , and SRSF2 were most frequently noted in our cohort, similar to other published reports 1,4 . Median OS in our study population was 8.1 months (identical to Saliba et al) after a longer median follow‐up duration since HMA‐Ven initiation (17.4 months); median EFS was very short at 4.3 months.…”

“…In summary, treatment with HMA-Ven resulted in an ORR of 58% in our cohort of 26 patients with CMML (ORR-62%) and post-CMML sAML (ORR-54%), which is comparable to the response rates reported by Saliba et al 1 Notably, ORR in our sAML cohort was significantly less compared to Montalban-Bravo et al (ORR of 81% in AML-MRC), although our study did not include patients on other Ven-based therapies than HMA-Ven. 4 We noted a reasonable ORR of 54% even in patients with prior HMA exposure.…”

“…We read with great interest the paper by Saliba et al 1 published recently in your journal. In this single‐institution study, authors describe the characteristics and outcomes of 20 patients with chronic myelomonocytic leukemia (CMML, n = 6) and CMML with blast transformation ( n = 14), who received treatment with venetoclax (Ven)‐based regimens, including 18 patients on a combination of hypomethylating agent and Ven (HMA‐Ven).…”

“…This study did not report the outcomes in HMA‐Ven cohort separately. Hence, the role of the HMA‐Ven in patients with CMML in real‐world settings remains unclear, with the two single‐institution studies published to date showing significant differences in outcome estimates 1,4 …”

How I diagnose and treat chronic myelomonocytic leukemia

“…Preclinical BH3 mimetic profiling data in CMML suggests that the malignant monocytes are addicted to mcl1 instead of bcl2 and that combination therapy with mcl1 and MAPK inhibitors might be a successful treatment strategy 101 . While prospective data is awaited, a small retrospective series including CMML patients with blast transformation demonstrated suboptimal (ORR-50% for CMML) response rates, with no significant difference from response rates seen with DNMTi alone 102 . c) Clinical trials: I actively seek out clinical trials for all our CMML patients given suboptimal response rates to conventional strategies.…”