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The median number of prior treatments was four
(range, 2-12), and 86 percent of patients were refractory
to their last therapy. The most common prior treatment
was bendamustine. At data cutoff, median treatment
duration was 6.5 months, with 65 patients (90%) off treatment due to progressive disease (38 patients), treatmentemergent adverse events (AEs) (15 patients), investigator
decision (7 patients), and death (5 patients).
Estimated median time to response was 2.6 months
(range, 1.6-11.0 months), while median response duration was 11 months (27 months in patients with complete
response). These findings, Dr. Zinzani and colleagues
concluded, demonstrate that idelalisib is a promising
option for high-risk relapsed/refractory FL patients with
limited treatment options.
TGR-1202
In a presentation by Matthew Lunning, DO, of the
University of Nebraska Medical Center and colleagues,
results were reported from a phase I trial evaluating the
combination of the anti-CD20 monoclonal antibody ublituximab with TGR-1202, a combination that has shown
strong synergistic activity in previous studies.3 TGR-1202
is a novel once-daily oral PI3K inhibitor with demonstrated clinical activity in B-cell lymphoma, and – importantly – without the hepatotoxicity typically associated
with similar agents, Dr. Lunning noted.
Subjects were heavily pre-treated relapsed/refractory
patients with NHL or CLL who were refractory to prior
PI3K or Bruton tyrosine kinase inhibitors. The median
number of prior treatment regimens was three (range,
1-9). Ublituximab was administered on days 1, 8, and 15
of cycles 1 and 2, and then day 1 of cycles 4, 6, 9, and 12.
TGR-1202 was administered orally once-daily.
Thirty-seven patients were evaluable for safety: 13
patients with CLL/small lymphocytic lymphoma, 12
with FL, nine with diffuse large B-cell lymphoma, two
with marginal zone lymphoma, and one with Richter’s
transformation. Grade 3 or 4 adverse events included
day 1 infusion reactions (3%), neutropenia (32%), and
diarrhea (3%). There was one instance of dose-limiting
toxicity: a patient with grade 3 neutropenia at study
entry worsened. Of note, there was no observed TGR1202–related hepatotoxicity.
Of the 29 patients evaluable for response, 13 of the
15 patients in the higher-dose cohorts (treated with
900 mg and 1,200 mg; 87%) remained progression-free
compared with six of 14 patients in the lower-dose
cohorts (450 mg and 600 mg; 43%). All but one of the
CLL patients remained progression-free with a median
follow-up time of 9 months. The data suggested that the
chemotherapy-free combination of ublitixumab and
TGR-1202 was active and well-tolerated in both iNHL
and CLL, Dr. Lunning reported.
Duvelisib
Finally, in a phase I study of duvelisib monotherapy in
18 treatment-naïve CLL patients presented by Susan
O’Brien MD, from University of California: Irvine, an
overall response rate of 82 percent was seen. Duvelisib
is an oral dual inhibitor of the PI3K-delta and PI3Kgamma isoforms currently in clinical development
for iNHL and CLL.4 According to Dr. O’Brien and
co-authors, because duvelisib inhibits both the PI3Kdelta and PI3K-gamma isoforms, it may be uniquely
positioned to inhibit key signals important in the
pathogenesis of B-cell malignancies.
In the study, patients received duvelisib 25 mg twice-daily and took the drug for a median of 53 weeks (range, 8-69
weeks). Ten patients remained on treatment, while eight
patients discontinued – including six due to AEs. Most of
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ASH Clinical News
these AEs were grade 1 or 2, Dr. O’Brien noted. The most
common grade ≥3 AEs were neutropenia (7 patients) and
ALT/AST increase (3 patients).
Evaluation of the pharmacodynamics data showed
that duvelisib had early clinical activity in thes RF