Promising Results for
Elotuzumab Push Monoclonal
Antibody Into Phase 3 Trial
Patients continued on the drug regimen as long as they were still
benefiting from the treatment. Those in the 10 mg/kg group had a
median number of 21 treatment cycles, while the 20 mg/kg arm had a
median number of 16 cycles. At data cut-off point, 13 patients in the
phase 2 trial (6 in the 10 mg/kg group, 7 in the 20 mg/kg group) were
still on treatment; 60 patients had discontinued due to disease progression (57%), adverse events (AEs; 20%), or other reasons (23%).
Overall response rate (ORR) was 84 percent: 92 percent in the 10
mg/kg group and 76 percent in the 20 mg/kg group. In terms of other
efficacy endpoints:
“Elotuzumab does appear to be adding to existing backbones of agents
in a very positive way and it does also appear to be well-tolerated,” Paul
G. Richardson, MD, first author of a dose-escalation study evaluating
the new agent’s use, told ASH Clinical News.
Elotuzumab is a humanized IgG1 monoclonal antibody that specifically targets the Signaling Lymphocytic Activation Molecule Family
Member 7, or SLAMF7, antigen. The drug works by targeting and killing
SLAMF-7-expressing myeloma cells, using direct activation and engagement of natural killer cells.
Early research of elotuzumab has been so encouraging, Dr. Richardson said, that it is the first monoclonal antibody for myeloma treatment
that has been moved into phase 3 testing. “Elotuzumab is a really exciting new antibody with great promise.”
Dr. Richardson, the clinical program leader and director of clinical research for the Jerome Lipper Multiple Myeloma Center at the
Dana-Farber Cancer Institute in Boston, presented final results from a
phase 1b/2 multi-center dose-escalation trial of elotuzumab, in combination with lenalidomide and dexamethasone, in RRMM patients.
The phase 2 portion of the trial randomly assigned 73 RRMM
patients who had never before been treated with lenalidomide to receive
either 10 mg/kg (n=36) or 20 mg/kg (n=37) of elotuzumab. All patients
also received lenalidomide and dexamethasone in standard doses.
• 14 percent of patients achieved either complete or “stringent” complete response
• 43 percent had a very good partial response
• 27 percent had a partial response
Adding the new agent elotuzumab to traditional regimens
of lenalidomide and low-dose dexamethasone has been
found to produce high response rates in patients with
relapsed/refractory multiple myeloma (RRMM).
Large Trial Demonstrates
New Treatment Option for
Relapsed or Refractory
Multiple Myeloma
Large Trial Demonstrates New Option for RRMM.
With more than 85 participating sites across Europe, the openlabel, phase 3b STRATUS trial was the largest of its kind to date to
evaluate pomalidomide, an orally administered immunodulatory
agent, plus low-dose dexamethasone in patients with RRMM.
Meletios Dimopoulous, MD, the first author of the study,
presented safety and efficacy results of the pomalidomide and
dexamethasone combination in 452 heavily pretreated patients; all
patients had previously failed treatment with lenalidomide and bortezomib and had been treated with a median of five prior therapies.
The combination of pomalidomide and dexamethasone had
no unexpected adverse events and was associated with proASHClinicalNews.org
Among all patients, median progression-free survival (PFS) was 29
months. Patients in the lower-dose elotuzumab group experienced longer median PFS (32 months vs. 25 months in the 20 mg/kg group).
The amount of time before the disease progressed was longer for
those in the 10 mg/kg group: median time to progression was 32.5
months for patients taking 10 mg/kg of elotuzumab, but 25 months
for the group taking 20 mg/kg.
The study was not powered to distinguish differences between
the treatment arms; however, a trend did seem to emerge, Dr.
Richardson noted. “The 10 mg/kg dose of elotuzumab does seem to
be doing better from a tolerability viewpoint, and it also seems to be
doing better from an efficacy point of view.” ●
Reference
• Richardson PG, Jagannath S, Moreau P, et al. “Final results for the 1703 phase 1b/2
study of elotuzumab in combination with lenalidomide and dexamethasone in
patients with relapsed/refractory multiple myeloma.” Abstract #302. Presented
at the American Society of Hematology Annual Meeting, December 8, 2014.
gression-free survival and overall survival of 4.3 months and
10.9 months, respectively. The most common grade 3-4 treatment-emergent adverse events with the combination therapy were
hematologic, and included neutropenia (39%), anemia (27%) and
thromocytopenia (19%).
“This combination produced solid results, demonstrating that
the combination is a standard of care for relapsed/refractory myeloma patients in whom lenalidomide and bortezomib therapies have
failed,” said Dr. Dimopoulous.
He believes that findings from the phase 3b STRATUS trial, together with earlier smaller trials into the use of pomalidomide and
dexamethasone in myeloma, should give treating practitioners the
confidence they need to use the combin