P774: CLINICAL OUTCOMES ASSOCIATED WITH AZACITIDINE MONOTHERAPY FOR TREATMENT-NAIVE PATIENTS WITH HIGHER-RISK MYELODYSPLASTIC SYNDROME (HR MDS): A SYSTEMATIC LITERATURE REVIEW AND META-ANALYSIS

Abstract

Background: Azacitidine (AZA) is a standard of care for patients with HR MDS; however, the number of large data sets describing outcomes of AZA monotherapy in HR MDS is limited. Aims: To aggregate clinical outcomes data associated with AZA monotherapy for treatment-naive patients with HR MDS. Methods: CENTRAL, EMBASE, and MEDLINE were searched to identify interventional, prospective, and retrospective observational studies using AZA monotherapy in treatment-naive HR MDS (defined as intermediate-2 or high risk by International Prognostic Scoring System [IPSS] or intermediate to very high risk by Revised IPSS). Inclusion of observational studies was limited to those with >20 patients in the AZA monotherapy arm. Responses according to International Working Group (IWG) 2000 or IWG 2006 criteria—including complete remission (CR) rate, overall response rate (ORR; defined as CR, marrow CR [mCR], partial remission, and hematologic improvement), overall survival (OS), duration of response (DOR), and time to response (TTR)—were extracted. All articles were reviewed by 2 independent abstractors. Response rates were synthesized using random-effects models; median of medians was used for OS, DOR, and TTR. Results: Of 3250 abstracts identified, 34 publications describing 16 studies met inclusion criteria: 5 randomized controlled trials (RCTs), 3 prospective studies, and 8 retrospective studies. None of the response endpoints were reported in all studies (Table). The pooled CR rates, reported in 2 RCTs (N=55), 1 prospective study (N=27), and 3 retrospective studies (N=509), were 14%, 11%, and 16%, respectively. The pooled CR rate across all studies (N=591) was 16% (95% CI, 13%-19%). The mCR rate from 1 RCT was 19% (95% CI, 10%-34%; N=42), and the pooled mCR rate from 2 retrospective studies was 18% (95% CI, 13%-26%; N=126). The pooled ORRs ranged from 44% to 55% across RCTs, prospective studies, and retrospective studies. The pooled median OS was 16.7 months in 3 RCTs (N=161), 16.5 months in a single prospective study (N=34), and 14.4 months in 5 retrospective studies (N=1472). The pooled median OS across all studies (N=1667) was 16.4 months (95% CI, 12.0-17.3 months). The pooled median DOR was 10.1 months (95% CI, 9.1-11.0 months), and the median TTR was 4.6 months (95% CI, 3.0-9.0 months). Table: - Outcomes in treatment-naive patients with HR MDS treated with AZA monotherapy Endpoint RCTs Total N Outcome(95% CI) Prospectivestudies Total N Outcome(95% CI) Retrospective studies Total N Outcome(95% CI) All studies Total N Outcome(95% CI) CR rate, % 2 55 14(6-31) 1 27 11(4-29) 3 509 16(13-20) 6 591 16(13-19) mCR rate, % 1 42 19(10-34) 0 - - 2 126 18(13-26) 3 168 19(13-25) ORR, % 3 159 50(42-57) 1 27 44(27-63) 4 967 55(42-67) 8 1153 52(44-60) Median OS, months 3 161 16.7(9.5-26.3) 1 34 16.5(10.4-21.9) 5 1472 14.4(11.6-17.3) 9 1667 16.4(12.0-17.3) Median DOR, months 1 20 9.1(6.0-NR) 0 - - 1 405 11.0 (NA) 2 425 10.1(9.1-11.0) Median TTR, months 1 42 4.6(2.0-6.5) 0 - - 2 493 6.0 (3.0-9.0) 3 535 4.6(3.0-9.0) NA, not available; NR, not reached. Summary/Conclusion: These findings provide evidence that benefit with AZA monotherapy in treatment-naïve patients with HR MDS is limited. Opportunity exists for novel therapies to increase CR rates and prolong survival.