title: Carfilzomib, rituximab, and dexamethasone (CaRD) treatment offers a neuropathy-sparing approach for treating Waldenström's macroglobulinemia.
abstract: Bortezomib frequently produces severe treatment-related peripheral neuropathy (PN) in Waldenström's macroglobulinemia (WM). Carfilzomib is a neuropathy-sparing proteasome inhibitor. We examined carfilzomib, rituximab, and dexamethasone (CaRD) in symptomatic WM patients naïve to bortezomib and rituximab. Protocol therapy consisted of intravenous carfilzomib, 20 mg/m2 (cycle 1) and 36 mg/m(2) (cycles 2-6), with intravenous dexamethasone, 20 mg, on days 1, 2, 8, and 9, and rituximab, 375 mg/m(2), on days 2 and 9 every 21 days. Maintenance therapy followed 8 weeks later with intravenous carfilzomib, 36 mg/m(2), and intravenous dexamethasone, 20 mg, on days 1 and 2, and rituximab, 375 mg/m(2), on day 2 every 8 weeks for 8 cycles. Overall response rate was 87.1% (1 complete response, 10 very good partial responses, 10 partial responses, and 6 minimal responses) and was not impacted by MYD88(L265P) or CXCR4(WHIM) mutation status. With a median follow-up of 15.4 months, 20 patients remain progression free. Grade ≥2 toxicities included asymptomatic hyperlipasemia (41.9%), reversible neutropenia (12.9%), and cardiomyopathy in 1 patient (3.2%) with multiple risk factors, and PN in 1 patient (3.2%) which was grade 2. Declines in serum IgA and IgG were common. CaRD offers a neuropathy-sparing approach for proteasome inhibitor-based therapy in WM. This trial is registered at www.clinicaltrials.gov as #NCT01470196.
authors.affiliation: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; and.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Treon
authors.affiliation: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Christina K
authors.initials: CK
authors.lastname: Tripsas
authors.affiliation: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Kirsten
authors.initials: K
authors.lastname: Meid
authors.affiliation: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Sandra
authors.initials: S
authors.lastname: Kanan
authors.affiliation: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Patricia
authors.initials: P
authors.lastname: Sheehy
authors.affiliation: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Stacey
authors.initials: S
authors.lastname: Chuma
authors.affiliation: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Lian
authors.initials: L
authors.lastname: Xu
authors.affiliation: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Patterson
authors.affiliation: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Diane
authors.initials: D
authors.lastname: Warren
authors.affiliation: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Zachary R
authors.initials: ZR
authors.lastname: Hunter
authors.affiliation: BioBridges Inc., Newton, MA.
authors.forename: Barry
authors.initials: B
authors.lastname: Turnbull
authors.affiliation: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; and.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Ghobrial
authors.affiliation: Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; and.
authors.forename: Jorge J
authors.initials: JJ
authors.lastname: Castillo
mesh_terms: D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage; D010523:Peripheral Nervous System Diseases / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*; D011379:Prognosis; D011446:Prospective Studies; D012074:Remission Induction; D000069283:Rituximab; D015996:Survival Rate; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009842:Oligopeptides; D000069283:Rituximab; C524865:carfilzomib; D003907:Dexamethasone