title: Azacitidine-lenalidomide (ViLen) combination yields a high response rate in higher risk myelodysplastic syndromes (MDS)-ViLen-01 protocol.
abstract: Azacitidine treatment is effective in higher risk MDS (HR-MDS), with less than 50 % response, lasting 2 years. Aza and lenalidomide (Len) have a potential synergistic effect. ViLen-01 phase IIa trial includes 6-month induction (Aza 75 mg/m(2)/day, days 1-5, Len 10 mg/day, days 6-21, every 28 days), 6-month consolidation (Aza 75 mg/m(2)/day, days 1-5, every 28 days), and 12-month maintenance (Len 10 mg/day, days 1-21, every 28 days). Response was evaluated according to IWG criteria. Totally, 25 patients enrolled, with an average of 76.3 years old (60-87), and 88 % with major comorbidities. Thirteen patients completed induction, 7 proceeded for consolidation, and 2 for maintenance. The overall response rate (ORR) was 72 % (18/25), with 6 (24 %) for CR, 3 (12 %) for marrow CR, and 9 (36 %) for hematologic improvement (HI). The 7 non-responding patients were on the study 3 days to 4.1 months. At 6 months, 4 of 6 evaluable patients achieved complete cytogenetic response and 2 with del (5q) at diagnosis. Adverse events (AEs) were as expected in these patients: grades III-IV, mainly hematologic-thrombocytopenia (20 patients) and neutropenia (13 patients). The common non-hematologic AEs were infections (14 patients), nausea (7), vomiting (7), diarrhea (7), and skin reactions (5). The median progression-free survival (PFS) was 12 ± 1.36 months, with median overall survival (OS) of 12 ± 1.7 months. Quality of life (FACT questionnaire) data were available for 12 patients with a tendency towards improved QoL. This trial with elderly HR-MDS patients with an expected poor prognosis demonstrates a high (72 %) response rate and a reasonable expected safety profile but a relatively short PFS and OS.
authors.affiliation: Department of Medicine A, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv, 64239, Israel. moshemt@tlvmc.gov.il.|Sackler Medical Faculty, Tel Aviv University, Tel Aviv, Israel. moshemt@tlvmc.gov.il.
authors.forename: Moshe
authors.identifier: http://orcid.org/0000-0001-7677-9119
authors.initials: M
authors.lastname: Mittelman
authors.affiliation: Kaplan Medical Center, Rehovot, Israel.|Hebrew University, Jerusalem, Israel.
authors.forename: Kalman
authors.initials: K
authors.lastname: Filanovsky
authors.affiliation: Rambam Medical Center, Haifa, Israel.|Technion, Haifa, Israel.
authors.forename: Yishai
authors.initials: Y
authors.lastname: Ofran
authors.affiliation: Rambam Medical Center, Haifa, Israel.|Technion, Haifa, Israel.
authors.forename: Hanna
authors.initials: H
authors.lastname: Rosenbaum
authors.affiliation: Sackler Medical Faculty, Tel Aviv University, Tel Aviv, Israel.|Rabin Medical Center, Petah Tikva, Israel.
authors.forename: Pia
authors.initials: P
authors.lastname: Raanani
authors.affiliation: Western Galilee Medical Center, Nahariya, Israel.|Bar-Ilan University, Safed, Israel.
authors.forename: Andrei
authors.initials: A
authors.lastname: Braester
authors.affiliation: Hebrew University, Jerusalem, Israel.|Hadassah Medical Center, Hebrew University, Jerusalem, Israel.
authors.forename: Neta
authors.initials: N
authors.lastname: Goldschmidt
authors.affiliation: Department of Medicine A, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv, 64239, Israel.|Sackler Medical Faculty, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ilya
authors.initials: I
authors.lastname: Kirgner
authors.affiliation: Department of Medicine A, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv, 64239, Israel.|Sackler Medical Faculty, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Herishanu
authors.affiliation: Department of Medicine A, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv, 64239, Israel.|Sackler Medical Faculty, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Chava
authors.initials: C
authors.lastname: Perri
authors.affiliation: Sackler Medical Faculty, Tel Aviv University, Tel Aviv, Israel.|Meir Medical Center, Kfar-Saba, Israel.
authors.forename: Martin
authors.initials: M
authors.lastname: Ellis
authors.affiliation: Department of Medicine A, Tel Aviv Sourasky Medical Center, 6 Weizmann St., Tel Aviv, 64239, Israel.|Sackler Medical Faculty, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Howard S
authors.initials: HS
authors.lastname: Oster
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000963:Antimetabolites / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology; D019175:DNA Methylation / Q000187:drug effects; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D011446:Prospective Studies; D011788:Quality of Life; D012306:Risk; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000963:Antimetabolites; D013792:Thalidomide; D000077269:Lenalidomide; D001374:Azacitidine
keywords: Azacitidine-lenalidomide; High-risk MDS; Myelodysplastic syndromes