title: Mature results of MM-011: a phase I/II trial of liposomal doxorubicin, vincristine, dexamethasone, and lenalidomide combination therapy followed by lenalidomide maintenance for relapsed/refractory multiple myeloma.
abstract: A previous interim report of MM-011, the first study that combined lenalidomide with anthracycline-based chemotherapy followed by lenalidomide maintenance for relapsed and/or refractory multiple myeloma (RRMM), showed promising safety and activity. We report the long-term outcomes of all 76 treated patients with follow-up ≥ 5 years. This single-center phase I/II study administered lenalidomide (10 mg on days 1-21 of every 28-day cycle), intravenous liposomal doxorubicin (40 mg/m(2) on day 1), dexamethasone (40 mg on days 1-4), and intravenous vincristine (2 mg on day 1). After 4-6 planned induction cycles, lenalidomide maintenance therapy was given at the last tolerated dose until progression, with or without 50 mg prednisone every other day. The median number of previous therapies was 3 (range, 1-7); 49 (64.5%) patients had refractory disease. Forty-three (56.6%) patients received maintenance therapy. Grade 3/4 adverse events occurred during induction and maintenance therapy in 48.7% and 25.6% of patients, respectively. Four (5.3%) treatment-related deaths occurred during induction. Responses were seen in 53.0% (at least partial response) and 71.2% (at least minor response) of patients. Overall, median progression-free survival and overall survival were 10.5 and 19.0 months, respectively; in patients with refractory disease these values were 7.5 and 11.3 months, respectively. Lenalidomide with anthracycline-based chemotherapy followed by maintenance lenalidomide provided durable control in patients with RRMM (ClinicalTrials.gov number, NCT00091624).
authors.affiliation: Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Lazaryan
authors.forename: Mohamad A
authors.initials: MA
authors.lastname: Hussein
authors.forename: Frederic J
authors.initials: FJ
authors.lastname: Reu
authors.forename: Beth
authors.initials: B
authors.lastname: Faiman
authors.forename: Becky
authors.initials: B
authors.lastname: Habecker
authors.forename: Mary
authors.initials: M
authors.lastname: Ann Karam
authors.forename: Janice
authors.initials: J
authors.lastname: Reed
authors.forename: Kimberly
authors.initials: K
authors.lastname: Hamilton
authors.forename: Joel
authors.initials: J
authors.lastname: Waksman
authors.forename: Kellie
authors.initials: K
authors.lastname: Bruening
authors.forename: Gordan
authors.initials: G
authors.lastname: Srkalovic
authors.forename: Steven
authors.initials: S
authors.lastname: Andresen
authors.forename: Matthew
authors.initials: M
authors.lastname: Kalaycio
authors.forename: John W
authors.initials: JW
authors.lastname: Sweetenham
authors.forename: Ronald
authors.initials: R
authors.lastname: Sobecks
authors.forename: Robert
authors.initials: R
authors.lastname: Dean
authors.forename: Robert
authors.initials: R
authors.lastname: Knight
authors.forename: Jerome B
authors.initials: JB
authors.lastname: Zeldis
authors.forename: Rachid
authors.initials: R
authors.lastname: Baz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D017053:Infection Control; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D000077269:Lenalidomide; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics / Q000628:therapy; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D016016:Proportional Hazards Models; D012074:Remission Induction; D016879:Salvage Therapy; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D013927:Thrombosis / Q000517:prevention & control; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D013792:Thalidomide; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D000077269:Lenalidomide