On Location ASH Meeting on Lymphoma Biology
“ X-1085 binds more strongly to
F
the [BCL6-BTB] protein than to
the natural ligand and was very
potent in vitro, in vivo, and in ex
vivo patient samples.”
—Mariano G. Cardenas, PhD
Infusion reactions: The incidence of infusion reactions
was 69% with the first infusion of GAZYVA. The incidence
of Grade 3 or 4 infusion reactions was 21% with 8% of
patients discontinuing therapy. The incidence of reactions
with subsequent infusions was 3% with the second 1000
mg and < 1% thereafter. No Grade 3 or 4 infusion reactions
were reported beyond the first 1000 mg infused.
Of the first 53 patients receiving GAZYVA on the trial,
47 (89%) experienced an infusion reaction. After this
experience, study protocol modifications were made to
require pre-medication with a corticosteroid, anti-histamine,
and acetaminophen. The first dose was also divided into
two infusions (100 mg on day 1 and 900 mg on day 2). For
the 45 patients for whom these mitigation measures were
implemented, 21 patients (47%) experienced a reaction
with the first 1000 mg and < 2% thereafter [see Dosage and
Administration (2)].
Neutropenia: The incidence of neutropenia reported as an
adverse reaction was 40% in the GAZYVA treated arm and
18% in the chlorambucil alone arm with the incidence of
serious adverse events being 1% and 0%, respectively
(Table 3). Cases of late onset neutropenia (occurring 28
days after completion of treatment or later) were 16% in
the GAZYVA treated arm and 12% in the chlorambucil
alone arm.
Infection: The incidence of infections was similar between
arms. Thirty-eight percent of patients in the GAZYVA
treated arm experienced an infection, 9% were Grade 3–4
and none were fatal.
Thrombocytopenia: The incidence of thrombocytopenia
reported as an adverse reaction was 15% in the GAZYVA
treated arm and 7% in the chlorambucil alone arm (Table
3). Five percent of patients in the GAZYVA treated arm
experienced acute thrombocytopenia (occurring within
24 hours after the GAZYVA infusion). The number of fatal
hemorrhagic events was similar between the treatment
arms, with 4 in the GAZYVA treated arm. However, all
fatal hemorrhagic events in patients treated with GAZYVA
occurred in Cycle 1.
Tumor Lysis Syndrome: The incidence of Grade 3 or 4 tumor
lysis syndrome was 2% in the GAZYVA treated arm versus
0% in the chlorambucil arm.
Musculoskeletal Disorders: Adverse events related
to musculoskeletal disorders, including pain (System Organ
Class) have been reported with GAZYVA with higher incidence
than in the comparator arm (17% vs. 13%).
6.2