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MEETING NEWS MYELOMA
BCMA Antibody Drug Conjugate Active in Patients With
Heavily Pretreated Myeloma
In a phase I study presented at the 2017 ASH Annual Meeting,
60 percent of patients with heavily-pretreated multiple
myeloma (MM) responded to treatment with the humanized
immunoglobulin G1 anti-B-cell maturation agent (BCMA)
antibody conjugate GSK2857916. Suzanne Trudel, MD, of the
University of Toronto, in Ontario, and colleagues presented
findings of the first-in-human, open-label BMA117159 trial.
The trial consisted of dose-escalation and -expansion phases.
In the dose-escalation phase, 38 patients received GSK2857916,
and the maximum tolerated dose (primary endpoint) was not
reached, so researchers selected 3.4 mg/kg as the recommended
phase II dose. The dose-expansion phase included 35 patients
(median age = 60 years; range = 46-75 years) who had received
prior treatment with alkylators, proteasome inhibitors (PIs),
immunomodulators (IMiDs), and hematopoietic cell transplan-
tation, if eligible.
BCMA expression was not required for eligibility, but patients
were required to have documented disease progression within
60 days of their last therapy.
More than half of participants (57%) received five or more
prior lines of therapy (range = 1->10 therapies). All patients
received prior PI therapy, and 97 percent were refractory.
Ninety-one percent of patients were refractory to IMiDs: 40
percent received prior daratumumab, and 37 percent were
refractory. Most patients (89%; n=31) were double-refractory
to both PIs and IMiDs.
Patients received GSK2857916 3.4 mg/kg administered
every three weeks as a one-hour intravenous infusion. They
received treatment until disease progression, unacceptable
toxicity, withdrawal of consent, or completion of 16 treatment
cycles. The median number of treatment infusions was five
(range = 1-13 infusions), and more than half (54%) received
five or more infusions.
In the dose-expansion phase, 21 patients responded to
treatment, for an overall response rate (ORR) of 60 pe rcent.
Responses included:
• 1 stringent complete response (CR)
• 2 CRs
• 15 very good partial responses (PRs)
• 3 PRs
Among those previously treated with daratumumab (n=14),
the ORR was 43 percent (n=6; 95% CI 17.7-71.1). Eighteen
of those who were double-refractory to an IMiD and PI
responded to treatment (ORR=58%), and five of the 12
patients who were double-refractory and had received prior
daratumumab responded (ORR=42%).
“Responses occurred early – usually within one or two doses
[of GSK2857916] – and, in most cases, were durable,” Dr. Trudel
said during her presentation. “Dose reductions did not lead to
loss of response.”
The median duration of response was not reached, and the
median progression-free survival was 7.9 months (range not
reported; 95% CI 3.1 to not reached).
All patients experienced at least one adverse event (AE), the
most common (occurring in ≥25% of patients) of which were
corneal events (63%), thrombocytopenia (57%), anemia (29%),
increased aspartate aminotransferase (29%), and cough (26%).
Corneal events occurred despite patients receiving steroid
eye drops for four days with each infusion. The most common
events (occurring in ≥20% of patients) were blurred vision,
dry eye, and photophobia, most of which were grade 1/2 and
reversible.
The most common grade 3/4 AEs (reported by ≥10% of
patients) were thrombocytopenia (34%) and anemia (14%).
Fourteen patients (40%) reported serious AEs.
Eight patients experienced infusion-related reactions that
occurred during first infusion. These resolved and did not recur
with subsequent infusions. Eighteen patients discontinued
GSK2857916 because of disease progression (n=15), AEs (n=2),
or patient decision (n=1), while 17 patients continue to receive
the drug.
“The target and therapeutic mechanisms of action differenti-
ate GSK2857916 from [other] MM [drugs],” the authors noted.
“GSK2857916 demonstrated … deep and durable responses
in heavily pretreated … [patients with] MM who have limited
treatment options.”
The study is limited by its small patient population and lack
of a comparator arm.
The researchers have also begun enrolling patients into a
lymphoma cohort to assess GSK2857916.
GlaxoSmithKline, Seattle Genetics, and BioWa supported the
study.
The authors report financial relationships with Astellas, Janssen,
Takeda, GlaxoSmithKline, Celgene, and Amgen.
REFERENCE
Trudel S, Lendvai N, Popat R, et al. Deep and durable responses in patients (pts)
with relapsed/refractory multiple myeloma (MM) treated with monotherapy
GSK2857916, an antibody drug conjugate against B-cell maturation antigen
(BCMA): preliminary results from part 2 of study BMA117159. Abstract #741.
Presented at the 2017 American Society of Hematology Annual Meeting,
December 11, 2017; Atlanta, GA.
March 2018
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