CLINICAL NEWS
Treatment was held because of DS in 11
patients (4.3%), but no cases of DS led to
permanent treatment discontinuation or
death. Disease progression was the most
common cause of treatment discontinu-
ation; 12.8 percent stopped treatment
because of AEs.
Among 125 patients with relapsed/
refractory AML who received ivosidenib
500 mg for a minimum of six months
(92 in dose-expansion and 33 in dose-
escalation phases), the rate of complete
response (CR) or CR with partial hemato-
logic recovery (primary endpoint) was 30.4
percent, which lasted for a median of 8.2
months (95% CI 5.5-12.0; range not pro-
vided). The median duration of response
was 6.5 months (range not provided). Of
those who achieved CR, 28 percent were
minimal residual disease–negative.
After 14.8 months of follow-up, the me-
dian overall survival (OS) was 8.8 months
(range = 6.7-10.2); the median OS was not
reached in those who achieved a CR but
was 9.3 months for non-responders (range
not reported).
Sources: Agios press release, February 15, 2018; DiNardo CD, De Botton
S, Stein EM, et al. Ivosidenib (AG-120) in mutant IDH1 AML and ad-
vanced hematologic malignancies: results of a phase 1 dose escalation
and expansion study. Abstract #725. Presented at the 2017 American
Society of Hematology Annual Meeting, December 11, 2017; Atlanta, GA.
Brentuximab Vedotin
Approved for Classical
Hodgkin Lymphoma
The FDA expanded the approval of bren-
tuximab vedotin to include the treatment
of adult patients with previously untreated
stage III or IV classical Hodgkin lym-
phoma (cHL) in combination with AVD
(doxorubicin, vinblastine, dacarbazine).
The approval was based on results
from the phase III ECHELON-1 clinical
trial. From November 19, 2012, through
January 13, 2016, 1,344 patients with
previously untreated stage III or IV cHL
were randomized to receive up to six cycles
of either ABVD (doxorubicin, bleomycin,
vinblastine, dacarbazine; n=670) or
brentuximab vedotin plus AVD (n=664).
The median age was 36 years (range =
18-83 years), 64 percent of patients in each
group had stage IV disease, and 58 percent
in each group had B symptoms.
Treatment with brentuximab vedotin
plus AVD reduced the risk of disease
progression, death, or initiation of new
therapy by 23 percent, compared with
ABVD (hazard ratio = 0.77; 95% CI 0.60-
0.98; p=0.03).
After a median follow-up of 24.9
months (range not provided), rates of
two-year modified progression-free
survival were significantly higher in the
brentuximab vedotin plus AVD group:
82.1 percent (95% CI 78.7-85.0) versus
77.2 percent (95% CI 73.7-80.4).
The most common AEs in each arm
ASHClinicalNews.org
were neutropenia, constipation, vomit-
ing, fatigue, and peripheral neuropathy.
Pulmonary toxicity was more frequent
and severe with ABVD (3% vs. <1%), but
neutropenia and peripheral neuropathy
were more common in the brentuximab
vedotin plus AVD arm.
Eighty-eight (13%) and 105 (16%)
patients, respectively, discontinued
treatment because of AEs. Serious AEs
included peripheral neuropathy; anaphy-
laxis; infusion-site reactions; hematologic,
pulmonary, and hepato-toxicities; serious
infections; tumor lysis syndrome; serious
dermatologic reactions; and gastrointesti-
nal complications.
There were 22 on-treatment deaths;
seven of nine deaths (78%) in the bren-
tuximab vedotin plus AVD group were
associated with neutropenia, and 11 of 13
(85%) in the ABVD group were associated
with pulmonary toxicity.
The drug has a boxed warning for
the risk of JC virus infection resulting in
progressive multifocal leukoencephalopa-
thy, a rare but serious brain infection that
can be fatal.
Brentuximab vedotin previously re-
ceived priority review and breakthrough-
therapy designation for this indication.
The drug also previously received FDA
approval for relapsed cHL, cHL after HCT
in patients at high risk of relapse or pro-
gression, and previously treated systemic
and primary cutaneous anaplastic large-
cell lymphoma.
• The diagnostic laboratory test using
NGS must have FDA approval or
clearance as a companion in vitro
diagnostic; an FDA-approved or
cleared indication for use in that
patient’s cancer; and resul