Program: Oral and Poster Abstracts
Session: 637. Myelodysplastic Syndromes – Clinical Studies: Poster II
Methods: Patients (pts) aged 18-75 years with ECOG performance status (PS) of 0–2 and no major comorbidities preventing administration of an intensified regimen of AZA, with IPSS int-2 or high MDS, CMML with WBC < 13,000/mm3 and marrow blasts > 10% , or AML with 20-30% marrow blasts (ie EU label for AZA) who had received no prior treatment for their MDS/AML except ESAs could be included. Treatment consisted of AZA 75mg/m2/d for 5 days every 14 days for 4 cycles (AZA-14, cycles 1-4). Patients achieving CR or PR then received 4 cycles of AZA 75mg/m2/d during 5 days every 21 days (AZA-21, cycles 5 to 8) followed by classical cycles of AZA 75mg/m2/d for 7 days every 28 days, to be continued until progression/relapse or toxicity arose. This schedule corresponded to a 30% increase in the number of days of AZA during the first 3 months of treatment. Patients not obtaining CR or PR after the initial 4 cycles of AZA-14 received 4 additional cycles of AZA 14 (cycles 5 to 8). Patients not obtaining CR, PR or HI after 8 cycles of AZA-14 were excluded from the trial. The primary endpoint was response after 4 and 8 cycles (IWG 2006 criteria). Median [IQR] are reported unless specified.
Results: 27 patients were included, of whom 1 was excluded for consent withdrawal. 26 patients (M/F: 19/7, median age 66) enrolled between 2011 and 2013, were thus analyzed, including 1 ARSI, 2 RCMD, 3 RAEB1, 13 RAEB2, 2 CMML and 5 AML (with 20 to 30% marrow blasts). Karyotype (IPSS) was favorable in 11 pts, intermediate in 6 patients and unfavorable in 9 pts. Median marrow blast was 13.5% (IQR 9.7-18.0), baseline platelet count was 72.5 G/l (43.5-177.0) including 69% with platelet<50 G/L, baseline Hb level was 9.8 g/dl (8.9-10.6), and baseline ANC was 1.2 G/l (0.6-2.3). IPSS was int-1 in 1, int-2 in 16 patients and high in 9 patients. With a median follow-up of 20 months, 342 cycles were administered (median 12/patient, including 23 (88%) patients who received 6 or more cycles). Cycle 2 was performed at a median of 14 (14-14) days after cycle 1 and had to be delayed beyond d15 in only 1 patient. Cycles 3 and 4, scheduled at d28 and d42, were slightly delayed in many pts (and were administered at a median of d35 and d51 from AZA onset). 1 pt terminated the study before cycle 4. Regarding toxicity, 25 SAEs (grade 3-4) were reported in 16 patients, including 21 infectious events, 1 being lethal.
After 4 cycles, 1 achieved CR, 6 PR, 7 marrow CR, 5 stable disease with HI (overall response rate 19/26=73.1%). Overall, after 8 cycles, the ORR was 22/26 (85%), including 4 CR, 6 PR, 11 mCR and 1 stable disease with HI. Median survival was 21 months, while one and 2-year overall survival rates were 73%[95CI: 58%;92%] and 41%[95CI: 25%;66%], respectively.
No prognostic factors for OS, including IPSS (p=0.63), bone marrow blast % (p=0.24), sex (p=0.42), IPSS cytogenetic group (p=0.30) and PS (p=0.64) was found.
Conclusion: In this population of relatively “fit” Higher risk MDS, an intensified schedule of AZA seems feasible without obvious increase in toxicity compared to the classical 7 day schedule of azacitidine. Cycles were delayed in a limited proportion of patients and no extra toxicities were observed. Both the ORR of 85% and the 73% overall survival at 1 year are encouraging.
Disclosures: Guerci-Bresler: ARIAD: Speakers Bureau ; BMS: Speakers Bureau ; Novartis: Speakers Bureau ; PFIZER: Speakers Bureau . Legros: ARIAD: Speakers Bureau ; Novartis: Research Funding , Speakers Bureau ; BMS: Speakers Bureau . Fenaux: Novartis: Honoraria , Research Funding ; Celgene Corporation: Honoraria , Research Funding ; Amgen: Honoraria , Research Funding ; Janssen: Honoraria , Research Funding .
See more of: Myelodysplastic Syndromes – Clinical Studies
See more of: Oral and Poster Abstracts
*signifies non-member of ASH