title: A phase 2 safety study of accelerated elotuzumab infusion, over less than 1 h, in combination with lenalidomide and dexamethasone, in patients with multiple myeloma.
abstract: Elotuzumab, an immunostimulatory SLAMF7-targeting monoclonal antibody, induces myeloma cell death with minimal effects on normal tissue. In a previous phase 3 study in patients with relapsed/refractory multiple myeloma (RRMM), elotuzumab (10 mg/kg, ∼3-h infusion), combined with lenalidomide and dexamethasone, demonstrated durable efficacy and acceptable safety; 10% (33/321) of patients had infusion reactions (IRs; Grade 1/2: 29; Grade 3: 4). This phase 2 study (NCT02159365) investigated an accelerated infusion schedule in 70 patients with newly diagnosed multiple myeloma or RRMM. The primary endpoint was cumulative incidence of Grade 3/4 IRs by completion of treatment Cycle 2. Dosing comprised elotuzumab 10 mg/kg intravenously (weekly, Cycles 1-2; biweekly, Cycles 3+), lenalidomide 25 mg (daily, Days 1-21), and dexamethasone (28 mg orally and 8 mg intravenously, weekly, Cycles 1-2; 40 mg orally, weekly, Cycles 3+), in 28-day cycles. Premedication with diphenhydramine, acetaminophen, and ranitidine (or their equivalents) was given as in previous studies. If no IRs occurred, infusion rate was increased in Cycle 1 from 0.5 to 2 mL/min during dose 1 (∼2 h 50 min duration) to 5 mL/min for the entire infusion by dose 3 and also during all subsequent infusions (∼1-h duration). Median number of treatment cycles was six. No Grade 3/4 IRs occurred; only one Grade 1 and one Grade 2 IR occurred, both during the first infusion. These data support the safety of a faster infusion of elotuzumab administered over ∼1 h by the third dose, providing a more convenient alternative dosing option for patients.
authors.affiliation: Institute for Myeloma and Bone Cancer Research, West Hollywood, California.
authors.forename: James
authors.identifier: http://orcid.org/0000-0003-1587-6104
authors.initials: J
authors.lastname: Berenson
authors.affiliation: Investigative Clinical Research of Indiana, Indianapolis, Indiana.
authors.forename: Robert
authors.initials: R
authors.lastname: Manges
authors.affiliation: Cancer Specialists of North Florida, Jacksonville, Florida.
authors.forename: Suprith
authors.initials: S
authors.lastname: Badarinath
authors.affiliation: Comprehensive Blood & Cancer Centers, Bakersfield, California.
authors.forename: Alan
authors.initials: A
authors.lastname: Cartmell
authors.affiliation: Texas Health Presbyterian Cancer Center, Dallas, Texas.
authors.forename: Kristi
authors.initials: K
authors.lastname: McIntyre
authors.affiliation: US Oncology Research and Texas Oncology, San Antonio, Texas.
authors.forename: Roger
authors.initials: R
authors.lastname: Lyons
authors.affiliation: Horizon Oncology Research, Lafayette, Indiana.
authors.forename: Wael
authors.initials: W
authors.lastname: Harb
authors.affiliation: Bristol-Myers Squibb, Princeton, New Jersey.
authors.forename: Hesham
authors.initials: H
authors.lastname: Mohamed
authors.affiliation: Bristol-Myers Squibb, Princeton, New Jersey.
authors.forename: Ali
authors.initials: A
authors.lastname: Nourbakhsh
authors.affiliation: US Oncology Research and Rocky Mountain Cancer Centers, Denver, Colorado.
authors.forename: Robert
authors.initials: R
authors.lastname: Rifkin
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage; D004334:Drug Administration Schedule; D006801:Humans; D000077269:Lenalidomide; D009101:Multiple Myeloma / Q000188:drug therapy*; D061214:Patient Safety; D011292:Premedication / Q000379:methods; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C546027:elotuzumab; D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide