title: Melphalan, prednisone, and thalidomide vs melphalan, prednisone, and lenalidomide (ECOG E1A06) in untreated multiple myeloma.
abstract: This phase 3 trial (Eastern Cooperative Oncology Group [ECOG] E1A06) compared melphalan, prednisone, and thalidomide (MPT-T) with melphalan, prednisone, and lenalidomide (mPR-R) in patients with untreated multiple myeloma (MM). A noninferiority design was used, and inferiority was defined as a progression-free survival (PFS) hazard ratio (HR) of MPT-T/mPR-R ≤0.82. A total of 306 patients enrolled, with a median age of 75.7 years. Median follow-up was 40.7 months. Median time on therapy was 12.1 months and 23.1 months for the 46.6% of treated patients who received maintenance, with no differences by arm. Median PFS was 21 months on MPT-T and 18.7 months on mPR-R (HR, 0.84; 95% confidence interval, 0.64-1.09). Overall survival was 52.6 months (MPT-T) vs 47.7 months (mPR-R) (P = .476). Per-protocol response rates were 63.6% (MPT-T) and 59.9% (mPR-R) (P = .557). Grade ≥3 nonhematologic toxicity was 59.5% for MPT-T vs 40.0% for mPR-R (P = .001). Second malignancies were observed in 18 MPT-T patients vs 14 mPR-R patients. Quality-of-life analysis favored mPR-R by induction end (P = .007). Use of MPT-T or mPR-R in elderly patients with untreated MM demonstrates no statistical or clinically relevant differences in response rates, PFS, and OS; however, quality of life at end of induction was improved and lower toxicity reported with mPR-R. This trial was registered at www.clinicaltrials.gov as #NCT00602641.
authors.affiliation: Division of Hematology, Mayo Clinic Arizona, Scottsdale, AZ;
authors.forename: A Keith
authors.initials: AK
authors.lastname: Stewart
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Susanna
authors.initials: S
authors.lastname: Jacobus
authors.affiliation: Division of Hematology, Mayo Clinic Arizona, Scottsdale, AZ;
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
authors.affiliation: Marshfield Clinic, Marshfield, WI;
authors.forename: Matthias
authors.initials: M
authors.lastname: Weiss
authors.affiliation: University of Wisconsin, Madison, WI;
authors.forename: Natalie S
authors.initials: NS
authors.lastname: Callander
authors.affiliation: Division of Hematology, Mayo Clinic, Jacksonville, FL; and.
authors.forename: Asher A
authors.initials: AA
authors.lastname: Chanan-Khan
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN.
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077269:Lenalidomide; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D016609:Neoplasms, Second Primary / Q000209:etiology; D011241:Prednisone / Q000008:administration & dosage; D011788:Quality of Life; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D013792:Thalidomide; D000077269:Lenalidomide; D008558:Melphalan; D011241:Prednisone