title: Lenalidomide, cyclophosphamide and dexamethasone (CRd) for newly diagnosed multiple myeloma: results from a phase 2 trial.
abstract: The combination of lenalidomide and low-dose dexamethasone is an effective treatment for multiple myeloma (MM). Addition of alkylating agents to lenalidomide or thalidomide results in increased response rates and deeper responses. We designed this trial to study the combination of cyclophosphamide, lenalidomide, and dexamethasone (CRd) as initial therapy for MM. Fifty-three patients with previously untreated symptomatic MM was enrolled. Patients received 4-week treatment cycles consisting of lenalidomide (25 mg daily for 3 weeks), dexamethasone (40 mg weekly), and cyclophosphamide (300 mg/m(2) weekly for 3 weeks). A partial response or better was seen in 85% of patients including 47% with a very good partial response or better. The toxicities were manageable with over 80% of planned doses delivered; six patients went off study for toxicity. The median progression free survival (PFS) for the entire group was 28 months (95% CI: 22.7-32.6) and the overall survival (OS) at 2 years was 87% (95% CI: 78-96). Importantly, 14 patients with high-risk MM had similar PFS and OS as the standard-risk patients (n = 39). CRd is an effective and well-tolerated regimen for upfront therapy of MM with high response rates and excellent 2-year OS, and is suitable for long-term therapy.
authors.affiliation: Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA. kumar.shaji@mayo.edu
authors.forename: Shaji K
authors.initials: SK
authors.lastname: Kumar
authors.forename: Martha Q
authors.initials: MQ
authors.lastname: Lacy
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Hayman
authors.forename: Keith
authors.initials: K
authors.lastname: Stewart
authors.forename: Francis K
authors.initials: FK
authors.lastname: Buadi
authors.forename: Jacob
authors.initials: J
authors.lastname: Allred
authors.forename: Kristina
authors.initials: K
authors.lastname: Laumann
authors.forename: Philip R
authors.initials: PR
authors.lastname: Greipp
authors.forename: John A
authors.initials: JA
authors.lastname: Lust
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
authors.forename: Steven R
authors.initials: SR
authors.lastname: Zeldenrust
authors.forename: P Leif
authors.initials: PL
authors.lastname: Bergsagel
authors.forename: Craig B
authors.initials: CB
authors.lastname: Reeder
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Russell
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Mikhael
authors.forename: David
authors.initials: D
authors.lastname: Dingli
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; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D009194:Myeloma Proteins / Q000032:analysis; D009503:Neutropenia / Q000139:chemically induced; D010352:Patient Dropouts; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D018931:Antineoplastic Agents, Hormonal; D009194:Myeloma Proteins; C085016:multiple myeloma M-proteins; D013792:Thalidomide; D003907:Dexamethasone; D003520:Cyclophosphamide; D000077269:Lenalidomide