Outcomes and molecular profile of oligomonocytic CMML support its consideration as the first stage in the CMML continuum

Abstract

Patients with oligomonocytic chronic myelomonocytic leukemia (OM-CMML) are currently classified according to the 2017 World Health Organization myelodysplastic syndromes classification. However, recent data support considering OM-CMML as a specific subtype of chronic myelomonocytic leukemia (CMML), given their similar clinical, genomic, and immunophenotypic profiles. The main purpose of our study was to provide survival outcome data of a well-annotated series of 42 patients with OM-CMML and to compare them to 162 patients with CMML, 120 with dysplastic type (D-CMML), and 42 with proliferative type (P-CMML). OM-CMML had significantly longer overall survival (OS) and acute myeloid leukemia-free survival than did patients with CMML, considered as a whole group, and when compared with D-CMML and P-CMML. Moreover, gene mutations associated with increased proliferation (ie, ASXL1 and RAS-pathway mutations) were identified as independent adverse prognostic factors for OS in our series. We found that at a median follow-up of 53.47 months, 29.3% of our patients with OM-CMML progressed to D-CMML, and at a median follow-up of 46.03 months, 28.6% of our D-CMML group progressed to P-CMML. These data support the existence of an evolutionary continuum of OM-CMML, D-CMML, and P-CMML. In this context, we observed that harboring more than 3 mutated genes, carrying ASXL1 mutations, and a peripheral blood monocyte percentage >20% significantly predicted a shorter time of progression of OM-CMML into overt CMML. These variables were also detected as independent adverse prognostic factors for OS in OM-CMML. These data support the consideration of OM-CMML as the first evolutionary stage within the proliferative continuum of CMML.

Graphical abstract

Figure 1.

Next-generation sequencing mutational profile of patients with OM-CMML, D-CMML, and P-CMML.

Figure 2.

Overall survival and AML-free survival by Kaplan-Meier analysis of patients with OM-CMML, D-CMML, and P-CMML. (A) OS analysis. Patients with OM-CMML had a significantly longer OS than did those with D-CMML (median OS, 72.02 vs 50.37 months; P = .007) and P-CMML (median OS, 72.02 vs 24.12; P < .001). (B) LFS by Kaplan-Meier analysis of patients with OM-CMML, D-CMML, and P-CMML. Patients with OM-CMML had a significantly longer LFS than did those with D-CMML (median LFS, 72.02 vs 50.37 months; P = .008) and P-CMML (median LFS, 72.02 vs 23; P < .001). OS and LFS were compared with 2-sided log-rank tests.

Figure 3.

Overall survival by Kaplan-Meier analysis of lower-risk patients according to CPSS, CPSS-P, and Mayo-prognostic model. (A) OS analysis. Patients with OM-CMML had a significantly longer OS than did those with D-CMML (median OS, 131.81 vs 62.36 months; P = .038) and P-CMML (median OS, 131.81 vs 41.46; P = .001). (B) OS by Kaplan-Meier analysis of lower-risk patients by CPSS-P. Patients with OM-CMML did not have a significantly longer OS than did those with D-CMML (median OS: 131.81 vs 74.65 months; P = .199), but presented a significantly longer OS than did those with P-CMML (median OS, 131.81 vs 45.04; P = .005). (C) OS by Kaplan-Meier analysis of lower-risk patients by the Mayo prognostic model. Patients with OM-CMML had a significantly longer OS than did those with D-CMML (median OS, 131.81 vs 62.36 months; P = .046) and P-CMML (median OS, 131.81 vs 38.4; P < .001). OS was compared with 2-sided log-rank tests.