Randomized phase II study of azacitidine alone or in combination with lenalidomide or with vorinostat in higher-risk myelodysplastic syndromes and chronic myelomonocytic leukemia: North American Intergroup Study SWOG S1117 Journal Article
| Authors: | Sekeres, M. A.; Othus, M.; List, A. F.; Odenike, O.; Stone, R. M.; Gore, S. D.; Litzow, M. R.; Buckstein, R.; Fang, M.; Roulston, D.; Bloomfield, C. D.; Moseley, A.; Nazha, A.; Zhang, Y.; Velasco, M. R.; Gaur, R.; Atallah, E.; Attar, E. C.; Cook, E. K.; Cull, A. H.; Rauh, M. J.; Appelbaum, F. R.; Erba, H. P. |
| Article Title: | Randomized phase II study of azacitidine alone or in combination with lenalidomide or with vorinostat in higher-risk myelodysplastic syndromes and chronic myelomonocytic leukemia: North American Intergroup Study SWOG S1117 |
| Abstract: | Purpose Azacitidine is standard, first-line therapy in higher-risk myelodysplastic syndromes (MDS). Whether azacitidine-based combinations with lenalidomide or vorinostat produce superior overall response rates (ORRs) to azacitidine is not known. Patients and Methods North American Intergroup Study S1117 is a phase II/III trial that randomly assigned patients with higher-risk MDS and chronic myelomonocytic leukemia (CMML) 1:1:1 to azacitidine (75 mg/m2/day on days 1 to 7 of a 28-day cycle); azacitidine plus lenalidomide (10 mg/day on days 1 to 21); or azacitidine plus vorinostat (300 mg twice daily on days 3 to 9). The primary phase II end point was improved ORR. Results Of 277 patients from 90 centers, 92 received azacitidine, 93 received azacitidine plus lenalidomide, and 92 received azacitidine plus vorinostat. Median age was 70 years (range, 28 to 93 years), 85 patients (31%) were female, and 53 patients (19%) had CMML. Serious adverse events were similar across arms, although combination-arm patients were more likely to undergo nonprotocol-defined dose modifications (P, .001).With a median follow-up of 23 months (range, 1 to 43 months), the ORR was 38% for patients receiving azacitidine, 49% for azacitidine plus lenalidomide (P = .14 v azacitidine), and 27% for azacitidine plus vorinostat (P = .16 v azacitidine). For patients with CMML, ORR was higher for azacitidine plus lenalidomide versus azacitidine (68% v 28%, P = .02) but similar for all arms across cytogenetic subgroups, as was remission duration and overall survival. ORR was higher with mutations in DNMT3A and lower for SRSF2, whereas ORR duration improved with fewer mutations. Lenalidomide dose reduction was associated with worse overall survival (hazard ratio, 1.30; P = .05). Conclusion Patients with higher-risk MDS treated with azacitidine-based combinations had similar ORR to azacitidine monotherapy, although patients with CMML benefitted from azacitidine plus lenalidomide. The efficacy of combination regimens may have been affected by dose modifications. Copyright © 2017 American Society of Clinical Oncology. All rights reserved. |
| Keywords: | adult; cancer survival; controlled study; treatment response; aged; aged, 80 and over; middle aged; chronic myelomonocytic leukemia; gene mutation; major clinical study; overall survival; leukemia, myelomonocytic, chronic; lenalidomide; thalidomide; clinical trial; drug dose reduction; drug efficacy; drug withdrawal; monotherapy; side effect; treatment duration; conference paper; follow up; antineoplastic agent; gene; infection; multiple cycle treatment; phase 2 clinical trial; antimetabolites, antineoplastic; heart disease; kidney disease; randomized controlled trial; antineoplastic combined chemotherapy protocols; cohort analysis; cytogenetics; continuous infusion; high risk patient; rash; gastrointestinal toxicity; disease severity; myelodysplastic syndrome; multicenter study; vorinostat; hydroxamic acids; mental disease; skin disease; phase 3 clinical trial; connective tissue disease; antineoplastic antimetabolite; neurologic disease; hepatobiliary disease; metabolic disorder; thorax disease; musculoskeletal disease; hydroxamic acid; azacitidine; hematologic disease; myelodysplastic syndromes; vascular disease; respiratory tract disease; leukemia remission; lymphatic system disease; clinical outcome; urinary tract disease; dnmt3a gene; mediastinum disease; nutritional disorder; very elderly; humans; human; male; female; priority journal; analogs and derivatives; infestation; srsf2 gene |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 35 |
| Issue: | 24 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2017-08-20 |
| Start Page: | 2745 |
| End Page: | 2753 |
| Language: | English |
| DOI: | 10.1200/jco.2015.66.2510 |
| PUBMED: | 28486043 |
| PROVIDER: | scopus |
| PMCID: | PMC5562170 |
| DOI/URL: | |
| Notes: | Conference Paper -- Export Date: 2 October 2017 -- Source: Scopus |
