title: Reduced-dose fludarabine, cyclophosphamide, and rituximab (FCR-Lite) plus lenalidomide, followed by lenalidomide consolidation/maintenance, in previously untreated chronic lymphocytic leukemia.
abstract: Fludarabine, cyclophosphamide, and rituximab (FCR) remains the standard of care for fit chronic lymphocytic leukemia (CLL) patients requiring first therapy. However, side effects can be significant, and patients with poor risk features have inferior outcomes. The purpose of this study was to evaluate reduced-dose FCR (FCR-Lite) plus lenalidomide (FCR(2) ) followed by lenalidomide maintenance as a strategy to shorten immunochemotherapy in untreated CLL. Patients received four to six cycles of FCR(2) . Patients who were minimal residual disease (MRD) negative in peripheral blood (PB) and bone marrow (BM) initiated 12 months of lenalidomide maintenance after either four or six cycles (based on MRD status). The primary study endpoint was the complete response (CR) rate after four cycles of FCR(2) . Twenty patients were evaluable. After four cycles of FCR(2) , response rates were: CR, 45.0%; CR with incomplete blood count recovery (CRi), 5.0%; partial response (PR), 45.0%; and stable disease (SD), 5.0%. BM and PB samples from 27.8% and 52.9% of patients, respectively, were MRD negative. After six cycles, response rates were: CR, 58.3%; CRi, 16.7%; and PR, 25.0%. BM and PB samples from 50.0% and 72.7% of patients, respectively, were MRD negative. Overall, 75% of evaluable patients achieved a CR or CRi following FCR(2) . After 17.4 months of median follow-up, one progression and one death occurred. Our findings suggest that FCR(2) combines encouraging clinical activity with acceptable toxicity in previously untreated CLL. Lenalidomide can be safely added to FCR and may reduce chemotherapy exposure without compromising outcomes.
authors.affiliation: Center for Chronic Lymphocytic Leukemia and Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Mato
authors.affiliation: Department of Medical Affairs, Celgene Corporation, Summit, New Jersey.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Foon
authors.affiliation: Lymphoma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Feldman
authors.affiliation: Center for Chronic Lymphocytic Leukemia and Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Schuster
authors.affiliation: Center for Chronic Lymphocytic Leukemia and Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Jakub
authors.initials: J
authors.lastname: Svoboda
authors.affiliation: Pathology Department, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Kar Fai
authors.initials: KF
authors.lastname: Chow
authors.affiliation: Lymphoma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Marisa
authors.initials: M
authors.lastname: Valentinetti
authors.affiliation: Lymphoma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Mary
authors.initials: M
authors.lastname: Mrkulic
authors.affiliation: Lymphoma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Kelly
authors.initials: K
authors.lastname: Azzollini
authors.affiliation: Lymphoma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gadaleta
authors.affiliation: Pathology Department, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Pritish K
authors.initials: PK
authors.lastname: Bhattacharyya
authors.affiliation: Lymphoma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Joshua
authors.initials: J
authors.lastname: Zenreich
authors.affiliation: Lymphoma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Lauren-Nicole
authors.initials: LN
authors.lastname: Pascual
authors.affiliation: Lymphoma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Kara
authors.initials: K
authors.lastname: Yannotti
authors.affiliation: Lymphoma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Kdiry
authors.affiliation: Department of Pharmacy and Clinical Services, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey.|Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
authors.forename: Christina
authors.initials: C
authors.lastname: Howlett
authors.affiliation: Center for Chronic Lymphocytic Leukemia and Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Lauren
authors.initials: L
authors.lastname: Strelec
authors.affiliation: Center for Chronic Lymphocytic Leukemia and Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: David
authors.initials: D
authors.lastname: Porter
authors.affiliation: Lymphoma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: Coleen
authors.initials: C
authors.lastname: Bejot
authors.affiliation: Lymphoma Division, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey.
authors.forename: André
authors.initials: A
authors.lastname: Goy
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D000069283:Rituximab; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D013792:Thalidomide; D003520:Cyclophosphamide; D000077269:Lenalidomide; D014740:Vidarabine; C024352:fludarabine