Page 79 - 2019_04-Haematologica-web

AZA or LEN plus AZA in MDS, CMML and low blast AML
achieving a complete cytogenetic response whilst 1 achieved a partial response..
Time to disease relapse or progression (Figure 2A)
No association with treatment arm was found for time to relapse after CR/PR or PD.
Median time to progression to AML (MDS and CMML patients by WHO criteria) or death (all patients) from any cause was 37.2 months in the AZA arm and 28.8 months in the LEN+AZA arm.
Progression free-survival (PFS) (Figure 2B)
PFS was measured from first day of treatment to date of first confirmed disease progression or death from any cause. Median PFS time on AZA was 31.2 months (95% CI 25.0-37.4) and on LEN+AZA was 19.8 months (95% CI 14.7-29.2) with no difference between the arms observed (Figure 2B, logrank P=0.12).
Overall survival (Figures 2C and 2D)
The median follow-up time (estimated with the inverse Kaplan-Meier method) was 47.2 months (range 0.7-59.5); median survival time on AZA was 38.8 months (95%CI 35.8-52.6) compared to 29.2 months on LEN+AZA (95%CI 19.8-35.1) (logrank P=0.2). Forty-one patients on AZA had died compared to 49 on LEN+AZA (Table 8). Cause of death was mostly due to disease progression and infections with 5 overall due to hemorrhage and 9 other/unknown. There was a significant difference in median overall survival in IPSS-R Very Low/Low-risk and Intermediate/High/Very High-risk groups (Figure 2D, logrank P<0.001).
Quality of Life (Figure 3)
Completion rates for the EORTC QLQ-C30 at base- line/screening was 96%, at C4D22 83%, C8D22 82% and C12D22 or at primary endpoint visit was 84%. The only effect of treatment on QoL scores during study was a higher rate of diarrhea in LEN+AZA arm.
Discussion
This randomized phase II study aimed to find out whether outcomes were improved for patients with high- er risk MDS, CMML and low blast AML by adding lenalidomide treatment to the established regimen of azacitidine. These two agents have shown synergistic activity in vitro, with promising early results of the com- bination treatment from smaller single arm clinical trials. In this study, there was excellent duration and delivery of treatment in both arms due to strong recognition of the value of prolonged therapy, particularly with a clinical benefit endpoint at 12 months. Despite this and the good tolerability of the combination, there was no improve- ment in response rates, clinical benefit or survival. As in the study by Sekeres et al.,21 we showed a trend towards improved responses without translation to improved clin- ical benefit or survival, though this study was not ade- quately powered to show a difference in overall survival. The lack of clinical benefit was not due to an excess of toxicity in the combination arm.
No subgroup in this study, including those with CMML, and in contrast to the recent report by Sekeres et al.,21 had improved responses with the addition of lenalidomide to
Figure 3. Quality of life differences on EORTC QLQ C30 questionnaire between treatment cohorts using GEE regression model
haematologica | 2019; 104(4)
707