CLINICAL NEWS
In this phase 2 study, brentuximab vedotin was
administered to 49 patients with DLBCL and 19 patients
with other B-cell lymphomas. Most patients had Stage III
or IV disease, more than half had received three or more
prior systemic therapies, and nearly all had received prior
rituximab.
Of 48 efficacy-evaluable DLBCL patients, eight (17%)
achieved a complete remission (CR) and 13 (27%) a
partial remission (PR), for an objective response rate
of 44 percent at a median follow-up of 4.6 months
from the first dose. Of the 19 patients with other B-cell
lymphomas, five (26%) had either a CR or PR.
Objective responses were also durable: 5.6 months in
all responders and 16.6 months in patients with a CR.
Thirteen percent of patients required dose
modifications, primarily due to episodes of neutropenia
and peripheral sensory neuropathy.
To explore the safety of combining brentuximab
vedotin and rituximab, researchers amended the study
protocol in January 2013 to include 15 patients with
histologically confirmed DLBCL. Patients in this cohort
experienced a similar number of treatment-emergent
adverse events as patients in the monotherapy cohort,
though these patients did have a shorter duration of
drug exposure (13% received >5 cycles versus 43% on
monotherapy). For the 13 efficacy-evaluable patients, the
ORR was 46 percent, including two with a CR and four
with a PR.
In one
“unanticipated”
finding of the
study, there was
no statistical
correlation
between response
and level of CD30
expression, the
investigators
noted. “Neither the
degree of surface
expression of
CD30 nor sCD30
levels correlated
with the likelihood
of response,” the
investigators
observed.
“However, all
responding
DLBCL patients
had elevated
sCD30 at baseline and also proved to have a quantifiable
level of CD30 expression by computer-assisted methods,
even if the visual assessment by immunohistochemistry
on central review did not suggest CD30 expression.”
Patients with primary mediastinal B-cell lymphoma
also experienced a relatively low response rate (one CR
out of six patients; 17% ORR), though reasons for this
poor response are unclear. “Mediastinal DLBCL does
not respond as well as other DLBCL subtypes to salvage
therapy in general, so it may just represent the inherent
drug resistance of this subtype,” Dr. Jacobsen told ASH
Clinical News.
“Future studies of combination therapy are warranted,”
he added. “The lack of correlation between CD30
expression and response is ^