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 3/4IRs by completion of treatment Cycle 2. Dosing comprised elotuzumab 10 mg/kg intravenously (weekly, Cycles 1-2; biweekly, Cycles 31), 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 31), 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.

Weekly carfilzomib, lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: A phase 1b study

“…Other early phase RRMM studies have reported deaths in early cycles. For example, Berenson and colleagues evaluated accelerated elotuzumab infusion in 70 patients with NDMM or RRMM, and reported two deaths (due to ischemic colitis and chronic obstructive lung disease) that occurred in patients who received only one cycle of treatment . Seven deaths were reported among 46 patients enrolled into a phase 1b study of panobinostat, lenalidomide, and dexamethasone .…”

Elotuzumab and dexamethasone for relapsed or refractory multiple myeloma patients: A retrospective study

“…Elotuzumab was infused weekly at 10 mg/kg for cycles 1 and 2 (28 days/cycle), and on days 1 and 15 during subsequent cycles. Infusion rate was increased, such that 5 mL/min (~1‐hour duration) was infused on cycle 1 day 15 and beyond . Dexamethasone 28 mg PO (3‐24 hours before) and 8 mg IV (immediately prior) preceded each infusion, with additional 40 mg given on weeks without elotuzumab starting with cycle 3.…”

“…Infusion rate was increased, such that 5 mL/min (~1-hour duration) was infused on cycle 1 day 15 and beyond. 4 Dexamethasone 28 mg PO (3-24 hours before) and 8 mg IV (immediately prior) preceded each infusion, with additional 40 mg given on weeks without elotuzumab starting with cycle 3. Standard pre-infusion therapy included acetaminophen 650 mg, ranitidine 50 mg IV or 150 mg PO, and diphenhydramine 25-50 mg, as well as acyclovir 400 mg BID as antiviral prophylaxis.…”

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma

“…11 75 The prescribing information states that the infusion rate may be increased to 5 mL/min after four treatment cycles, however a phase II safety study found no increase in AEs with a faster infusion of elotuzumab administered over 1 hour from the third dose onward. 88 ELOQUENT-2 and ELOQUENT-3 both gave elotuzumab at 10 mg/kg intravenous weekly for the first 8 weeks. However, in ELOQUENT-2, 10 mg/ kg was continued every 2 weeks for cycles 3 and beyond whereas in ELOQUENT-3, elotuzumab was given 20 mg/ kg intravenous every 4 weeks for cycle 3 and beyond.…”