Japanese trial meets ORR primary endpoint.
This article first appeared January 3, 2018 on Medpage Today.
By Ed Susman
ATLANTA – The combination of elotuzumab (Empliciti) with lenalidomide (Revlimid) plus dexamethasone led to objective response rates (ORR) in more than 80% of newly diagnosed multiple myeloma patients, researchers said here.
In a phase II, open-label trial of more than 80 patients, 89% treated with the three-drug combo achieve an ORR versus 73% treated with the lenalidomide/dexamethasone after a minimum of 6 months follow-up, reported Mitsuo Hori, MD, PhD, of Ibaraki Perfectual Central Hospital in Ibaraki, Japan, and colleagues.
In addition, increasing the infusion rate to 5 mL/minute from a standard of 2 mL/minute in the experimental arm of the trial did not increase injection site reactions among the 40 patients randomized to receive elotuzumab, they said in a presentation at the American Society of Hematology (ASH) annual meeting.
"In this first report of elotuzumab plus lenalidomide/dexamethasone treatment of patients with newly-diagnosed multiple myeloma, the primary endpoint of objective response rate was met," the authors wrote. "Elotuzumab in combination with lenalidomide and dexamethasone had an acceptable safety profile in this patient population. These data suggested that this combination with a faster infusion rate of 5 mL/minute was effective and well tolerated in Japanese patients with newly-diagnosed multiple myeloma."
The three-drug regimen has been approved in Japan for the treatment of relapsed/refractory multiple myeloma, the authors explained. Elotuzumab is a humanized IgG1 monoclonal antibody that binds to SLAMF7 expressed on myeloma and natural killer (NK) cells. It has a dual mode of action, by causing targeted myeloma cell death by directly activating NK cells and enhances NK cell-mediated antibody-dependent cellular cytotoxicity, they added.
The researchers enrolled patients newly diagnosed with multiple myeloma who were ineligible for high-dose chemotherapy plus hematopoietic cell transplantation.
They were randomized 1:1 to intravenous elotuzumab 10/mg/weekly for cycles 1 and 2, and then were treated every 2 weeks for the next 16 cycles. They were treated with a dose of 20 mg elotuzumab monthly after that, plus lenalidomide or were treated with lenalidomide alone in a 28-day cycle until disease progression or unacceptable toxicity.
All patients in the elotuzumab arm received premedication prior to elotuzumab to mitigate infusion reactions.
At baseline, median patient age was 72. Patients on elotuzumab were able to take a median of 13 cycles of treatment compared with 11.5 cycles as the median for the patients taking lenalidomide/dexamethasone.
The study's primary endpoint was to determine if treatment with the combination could achieve at least a 71% objective response rate based on investigator assessment. Hori's group reported that two stringent complete responses were achieved in the three-drug treatment arm and one stringent complete response was observed in doublet arm. One other person achieved an investigator-determined complete response with elotuzumab and two patients achieved a complete response with lenalidomide/dexamethasone.
Fifteen of the patients treated with elotuzumab achieved a very good partial response compared with nine patients receiving the comparator drugs. Objective partial response were reported in 17 patients on elotuzumab and 19 patients on lenalidomide/dexamethasone.
The researchers said the remaining five patients on elotuzumab maintained stable disease as did seven of the patients on lenalidomide/dexamethasone. Only one of the 82 patients in the trial had progressive disease, and that person was taking the doublet. Three patients on the doublet were not available for evaluation.
Adverse events were reported in all the patients on elotuzumab and in 41 of 42 patients on lenalidomide/dexamethasone alone. The most common adverse events was constipation in 43% of the elotuzumab patients and in 31% of the patients getting the doublet.
Diarrhea was experienced by 38% of the elotuzumab patients and in 21% of the doublet patients. Pyrexia was reported in 35% of the elotuzumab patients compared with 7% of the lenalidomide/dexamethasone. About 28% of elotuzumab patients complained of a rash compared with 36% of the patients taking lenalidomide/dexamethasone-treated patients.
Nasopharyngitis was reported by 25% of the patients using elotuzumab and 26% of those on lenalidomide dexamethasone. Dysgeusia (impaired taste) was reported by 23% of the elotuzumab cohort and by 19% of the comparator group. Malaise was reported by 23% of the elotuzumab patients and by 2% of the lenalidomide/dexamethasone patients.
The authors reported that a secondary primary malignancy was reported in one patient in the three-drug arm (rectum) and one patient in the two-drug arm (lung).
The combination regiment had a comparable safety profile when given at 10 mg/kg weekly, or every 2 weeks up to cycle 18, or at 20 mg/kg monthly from cycle 19 onwards, they noted, adding that profession-free survival data were not mature at the time of the ASH presentation.