Does the IPSS-M Have Utility Beyond MDS?

The Molecular International Prognostic Scoring System (IPSS-M) isn’t just for myelodysplastic syndromes (MDS). It can also be used for risk stratification in chronic myelomonocytic leukemia (CMML) and may be “ important in community settings where CMML is misdiagnosed as MDS,” according to research presented at the annual meeting of the Society of Hematologic Oncology in Houston.

After retrospectively comparing IPSS-M with three other molecularly integrated risk-stratification models in patients with CMML, a research team from the H. Lee Moffitt Cancer Center and Research Institute found that IPSS-M performed comparably to the clinical/molecular CMML-specific prognostic scoring system (CPSS-Mol) and better than the Mayo Molecular Model (MMM) and the Groupe Francophone des Myélodysplasies (GFM) model.

The study was presented by Luis Aguirre, MD, of the Moffitt Cancer Center and the Dana-Farber Cancer Institute in Boston.

“The IPSS-M can be used reliably in CMML and shows comparable prognostic accuracy to the CPSS-Mol,” the study’s authors wrote.

Recently introduced for MDS, the IPSS-M demonstrated improved accuracy over the mutation-agnostic revised International Prognostic Scoring System (IPSS-R) in that application. The Moffitt research team sought in their study to determine if IPSS-M could also apply to CMML and to compare its performance with other risk-stratification models.

They retrospectively gathered clinical and molecular data from CMML patients treated at Moffitt and calculated mean IPSS-M scores. Next, they used correlative analysis to compare the performance of the four risk models.

The researchers said they found 987 driver point mutations involving 21 genes across the 367 patients in the study. At least one mutation was found in 352 (96%) of the patients, most commonly TET2, SRSF2, ASXL1, RUNX1, and NRAS.

With the IPSS-M, 26 (7%) patients were categorized as very-low risk, 108 (29%) as low risk, 76 (21%) as moderate-low risk, 58 (16%) as moderate-high risk, 65 (18%) as high risk, and 34 (9%) as very-high risk. These risk categories had median overall survival of 5.0 years (very-low risk), 5.1 years (low risk), 3.9 years (moderate-low risk), 2.6 years (moderate-high risk), 1.7 years (high risk), and 1.1 years (very-high risk).

In addition, the four-year cumulative acute myeloid leukemia (AML) incidence by IPSS-M risk category was 2% (very-low risk), 14% (low risk), 17% (moderate-low risk), 18% (moderate-high risk), 25% (high risk), and 14% (very-high risk).

After comparing the respective model results, the researchers found that CPSS-Mol and IPSS-M (c-index of 0.71 for both) produced better overall survival predictions than the MMM (c-index of 0.60) and GFM (c-index of 0.65).

With the IPSS-M, 202 (57%) of patients were restratified and 15 (22%) of patients categorized as low-risk by CPSS-Mol were upstaged, according to the researchers.

Of the 367 patients, 87 (23.7%) developed AML, 34 (9.2%) by one year, 60 (16.3%) by two years, and 79 (21.5%) by four years. The researchers found significant (P<.05) segregation between IPSS-M and CPSS-Mol groups and AML risk. CPSS-Mol led the way with 66% accuracy, followed by IPSS-M (63%), MMM (57%), and GFM (52%).

The results achieved by IPSS-M can play a role in community settings where CMML can be misdiagnosed as MDS, according to the authors.

“In such instances, using the IPSS-M is unlikely to adversely impact outcomes when used to guide treatment decisions,” they wrote.

Reference

Aguirre L, Ali NA, Sallman D, et al. A comprehensive assessment of the Molecular International Prognostic Scoring System (IPSS-M) and other molecularly integrated risk stratification models in chronic myelomonocytic leukemia (CMML). Abstract MDS-266. Presented at the Eleventh Annual Meeting of the Society of Hematologic Oncology; September 6-9, 2023; Houston, Texas.