Literature Scan
Examining Daratumumab Monotherapy
in Heavily Pretreated and Refractory Multiple
Myeloma Patients
Patients with multiple myeloma (MM) who are refractory to proteasome inhibitors and immunomodulatory drugs have poor prognoses
and limited treatment options. Recently, though, preclinical studies
have shown that the anti-CD38 monoclonal antibody daratumumab has
demonstrated anti-myeloma activity by inducing target-cell killing of
CD38-expressing tumor cells.
Based on those results, Henk M. Lokhorst, MD, PhD, from the
Department of Hematology of the VU University Medical Center in
Amsterdam, Netherlands, designed a two-part, open-label, multicenter,
phase I/II evaluating response to daratumumab treatment in patients
with relapsed MM or relapsed and refractory MM.
“These results compare favorably with other novel agents explored
in comparable settings. Single-agent daratumumab may become a novel
option for patients with double-refractory MM,” Dr. Lokhorst told ASH
Clinical News. “These data suggest that a new treatment era for MM may
be in sight. I believe monoclonal antibodies, of which daratumumab may
be one of the most potent, will become a standard in newly diagnosed
and relapsed MM.”
Patients were eligible for study inclusion if they were 18 years of age
or older, had a life expectancy of at least three months, had an Eastern
Cooperative Oncology Group score of two or less, and had a measurable level of M protein or free light chains according to the International
Myeloma Working Group (IMWG) guidelines.
The study’s primary endpoint was safety, which was evaluated based
on the frequency and severity of adverse events (AEs). Secondary endpoints included pharmacokinetics, objective response according to the
IMWG response criteria for MM, time to disease progression, duration
of response, progression-free survival (PFS), and overall survival (OS).
The study was divided into two parts:
• Part 1 (dose-escalation
phase): A total of 32 patients
in 10 cohorts received
daratumumab at doses
of 0.005 mg/kg to 24 mg/
kg. All patients received
a predose followed by a
three-week washout period
for assessment of safety
and pharmacokinetics.
Then a second predose was
administered, followed by six
full infusions administered
weekly, making the total
treatment period eight
weeks.
“A new treatment era for
multiple myeloma may be in
sight. ... I believe
monoclonal
antibodies will
become standard in newly
diagnosed and
relapsed MM.”
—HENK M. LOKHORST, MD, PhD
40
ASH Clinical News
• Part 2 (dose-expansion
phase): A total of 30
patients received 8 mg/