Impact of Available Therapies on Survival of Very Elderly Myelodysplastic Syndrome (MDS) Patients (Age above 75 yrs)

Objective:

Very elderly MDS patients (≥75 years) have limited therapeutic options and are usually ineligible for allogeneic stem cell transplantation. We aimed to study the impact of available MDS therapies on very elderly MDS patients and their correlation with patient demographics, performance status(PS) disease characteristics and patient outcomes.

Methods:

We performed a retrospective analysis of MDS patients ≥75 years diagnosed and treated at the University of Alabama at Birmingham from 2008 to 2014, with a minimum followup of 12 months. We analyzed demographics, ECOG PS, karyotypic risk categories as defined by the IPSS scoring system, blast percentage, IPSS and R-IPSS scores and overall survival (OS) in this population. We stratified patients based on therapy into two groups - the hypomethylating agent (HMA) group (defined as receiving therapy with ≥ 1 cycle of HMA; Azacitidine or Decitabine or both) and the non-HMA group, which included treatment with supportive transfusions, erythropoietin stimulating agents (ESAs), lenalidomide and cytotoxic chemotherapy. We analyzed group differences for all the parameters mentioned above using chi square test for categorical variables, and t test and Mann Whitney u-test for mean and medians respectively. In addition, OS was examined using Kaplan Meier curves using the log rank test. We used univariate and multivariate analysis to examine the effects of variables of interest on OS.All results were considered statistically significant at α=0.05 level.

Results:

The study population included 58 patients of which 35 patients were males (60%). Median age was 78 years. Forty patients (71%) of patients had good, 6% had intermediate and 23% had poor karyotypic profiles by the IPSS scoring system. ECOG ≥2 was observed in 44% of the patients with no significant differences in both groups. Average IPSS and R-IPSS scores were 1.2 and 4.5 respectively. Median OS for the entire study population was noted to be 15.5 months (7-34m). There were 25 patients in the HMA group and 33 patients in the non-HMA group. The blast percentage was higher in HMA group (20.5% vs 9.4%) compared to non-HMA group. More patients had a good karyotypic profile in the non-HMA group when compared to HMA group (80% vs 60%). There was a statistically significant difference between the mean IPSS and R-IPSS prognostic scores in non-HMA and HMA group (0.9 vs 1.7, p=0.010 and 3.5 vs 5.5, p=0.002) respectively. There was no significant difference in median overall survival between the non-HMA and HMA group (16.5 m (7-53) vs 15.5 m (5-19) p=0.278) respectively but the mean survival rates between non-HMA and HMA group were statistically different (32.81 vs 15.85, p=0.034). According to the log rank test, a statistical difference (p=0.027) in survival estimates was observed between the two groups on Kaplan Meier curve, where the HMA group had a significantly shorter survival compared to the non-HMA group. In the univariate analysis for the entire sample, higher IPSS score; R-IPSS score, and higher blast percentage were associated with increased rate of events. Moreover, rates of events were found to be lower in patients who did not receive HMA therapy (HR - 0.45, p=0.033), however in multivariable analysis, only higher blast percentage was associated with increased rate of events (HR - 1.06 p=0.025 95% CI - 1.004-1.11). Patients in the HMA group received average of 7.8 cycles. After stopping HMA therapy, 10 patients received other therapies including cytotoxic chemotherapy, hydroxyurea and lenalidomide, 4 were enrolled in a clinical trial, 9 received supportive transfusions and ESAs while 2 died immediately afterwards.

Conclusion:

Our study did not find a difference in median OS between patients who received HMA therapy versus non-HMA therapy in this population of very elderly MDS patients. Patients who received HMA therapy had a higher risk karyotypic profile, increased blast percentage and higher IPSS and R-IPSS scores. The average number of HMA cycles they received was 7.8, indicating adequate therapy. However, we could not evaluate transfusion needs, hospitalizations or other quality of life measures in these 2 groups. In conclusion, further studies need to be done to better evaluate various MDS therapies and their impact on quality of life and survival in this very elderly population with a higher comorbidity burden, possibly limiting the benefit of these treatments typically seen in younger MDS patients.