Prognosis of patients with intermediate risk IPSS-R myelodysplastic syndrome indicates variable outcomes and need for models beyond IPSS-R

Abstract

The International Prognostic Scoring System-Revised (IPSS-R) is one standard for myelodysplastic syndrome (MDS) risk stratification. It divides patients into five categories including an intermediate subset (IPSS-R int-risk). Outcomes and clinical interventions for patients with IPSS-R int-risk are not well defined. We performed an analysis of outcomes of this group of patients. Out of 3167 patients, a total of 298 were identified with IPSS-R int-risk MDS and retrospectively analyzed to assess characteristics affecting outcomes. Cox proportional hazard models for overall survival (OS) were performed to identify statistically significant clinical factors that influence survival. Age of 66 years or greater, peripheral blood blasts of 2% or more, and history of red blood cell (RBC) transfusion were significantly associated with inferior survival. Based on these features, MDS patients with IPSS-R int-risk were classified into two prognostic risk groups for analysis, an int-favorable group and an int-adverse group, and had significantly divergent outcomes. Sequential prognostication was validated using two independent datasets comprising over 700 IPSS-R int-risk patients. The difference in median survival between int-favorable and int-adverse patients was 3.7 years in the test cohort, and 1.8 and 2.0 years in the two validation cohorts. These results confirm significantly variable outcomes of patients with IPSS-R int-risk and need for different prognostic systems.

Figure 1.. Heterogeneity and divergent outcomes among IPSS-R intermediate-risk patients.

A: Variability and distribution of IPSS-R int-risk MDS patients. Top panel shows distribution of survival times vs. age. Bottom panel shows histogram of overall survival (bin width=6 months). Black curve shows non-linear fit of histogram of non-censored survival times using two Gaussian curves. B: Distribution of patients by sequentially stratification, based on the sum of three classification parameters: age (0 or 2 points), PB blasts (0 or 1 point), and RBC transfusion history (0 or 1 point). Each numerical score is subdivided to indicate how patients achieved specified scores. C: Overall survival among patients with IPSS-R intermediate-risk MDS according to two prognostic groups sequentially stratified as described, according to age, PB blasts, and transfusion history. D: Transfused units of red blood cells and platelets per patient year among int-favorable and int-adverse patients who required transfusions after diagnosis of MDS (p=<0.0001 for both red blood cells and platelets).

Figure 2.. IPSS classification of test cohort and survival of external validation cohorts.

A: Distribution of intermediate-favorable (int-fav) and intermediate-adverse (int-adv) test cohort groups when classified by IPSS. Survival for the two sequentially stratified prognostic groups using proposed risk score described. B: Survival based on sequential score for test cohort patients classified as IPSS intermediate-1 (int-1) risk. C: Survival based on sequential score for test cohort patients classified as IPSS intermediate-2 (int-2) risk. D: Survival of external validation cohort 1, IPSS-R int-risk patients from outside institution (n=111), classified by sequential scoring as int-favorable vs. int-adverse. E: Survival of external validation cohort 2, IPSS-R int-risk patients from outside institution (n=616), classified by sequential scoring as int-favorable vs. int-adverse.