title: Lenalidomide, cyclophosphamide, and dexamethasone (CRd) for light-chain amyloidosis: long-term results from a phase 2 trial.
abstract: Light-chain (AL) amyloidosis remains incurable despite recent therapeutic advances. Given the activity of the lenalidomide-alkylating agent combination in myeloma, we designed this phase 2 trial of lenalidomide, cyclophosphamide, and dexamethasone in AL amyloidosis. Thirty-five patients, including 24 previously untreated, were enrolled. Nearly one-half of the patients had cardiac stage III disease and 28% had ≥ 3 organs involved. The overall hematologic response (≥ partial response [PR]) rate was 60%, including 40% with very-good partial response or better. Using serum-free light chain for assessing response, 77% of patients had a hematologic response. Organ responses were seen in 29% of patients and were limited to those with a hematologic response. The median hematologic progression-free survival was 28.3 months, and the median overall survival was 37.8 months. Hematologic toxicity was the predominant adverse event, followed by fatigue, edema, and gastrointestinal symptoms. A grade 3 or higher toxicity occurred in 26 patients (74%) including ≥ grade 3 hematologic toxicity in 16 patients (46%) and ≥ grade 3 nonhematologic toxicity in 25 patients (71%). Seven patients (20%) died on study, primarily because of advanced disease. Lenalidomide, cyclophosphamide, and dexamethasone (CRd) is an effective combination for treatment of AL amyloidosis and leads to durable hematologic responses as well as organ responses with manageable toxicity. The trial was registered at www.clinicaltrials.gov (NCT00564889).
authors.affiliation: Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA. kumar.shaji@mayo.edu
authors.forename: Shaji K
authors.initials: SK
authors.lastname: Kumar
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Hayman
authors.forename: Francis K
authors.initials: FK
authors.lastname: Buadi
authors.forename: Vivek
authors.initials: V
authors.lastname: Roy
authors.forename: Martha Q
authors.initials: MQ
authors.lastname: Lacy
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
authors.forename: Jacob
authors.initials: J
authors.lastname: Allred
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Laumann
authors.forename: Leif P
authors.initials: LP
authors.lastname: Bergsagel
authors.forename: David
authors.initials: D
authors.lastname: Dingli
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Mikhael
authors.forename: Craig B
authors.initials: CB
authors.lastname: Reeder
authors.forename: A Keith
authors.initials: AK
authors.lastname: Stewart
authors.forename: Steven R
authors.initials: SR
authors.lastname: Zeldenrust
authors.forename: Philip R
authors.initials: PR
authors.lastname: Greipp
authors.forename: John A
authors.initials: JA
authors.lastname: Lust
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Russell
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000686:Amyloidosis / Q000188:drug therapy* / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000378:metabolism; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007147:Immunoglobulin Light Chains; D013792:Thalidomide; D003907:Dexamethasone; D003520:Cyclophosphamide; D000077269:Lenalidomide