Study Shows Duvelisib Has Marked Response, Survival Benefit in Difficult-to-Treat Leukemia and Lymphoma Compared with Standard Therapy
Published on: October 04, 2018
(WASHINGTON, October 4, 2018) — For some patients with difficult-to-treat
leukemia and lymphoma, the investigational oral medicine duvelisib may
significantly improve disease outcomes, according to phase III
trial data published today in the journal Blood.
The DUO trial studied the head-to-head comparison of duvelisib
versus ofatumumab, an approved standard-of-care chemotherapy for relapsed or treatment-resistant
chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). According
to the study, duvelisib extended the progression-free survival from a median of
9.9 months on ofatumumab to 13.3 months. Duvelisib’s benefit also appeared to
extend to patients with high-risk genetic mutations and poorer prognoses.
“The way we treat patients with CLL is changing rapidly as
we move from standard chemotherapy-based approaches to more targeted
therapies,” said principal investigator Ian W. Flinn, MD, PhD, Director of the
Lymphoma Research Program at Sarah Cannon Research Institute in Nashville.
“Based on these data, duvelisib may offer a new treatment option for patients
who otherwise may have limited options.”
In sub-group analyses, researchers found duvelisib worked
just as well as ofatumumab among the hardest-to-treat cases, including those patients
with p17 deletion or p53 abnormalities, who have few available therapeutic
options. Patients with these genetic mutations who took duvelisib had a 60
percent reduction in their risk of cancer progression or death compared to
similar patients in the ofatumumab group.
“These are patients in whom traditional chemotherapy doesn’t
work,” said Dr. Flinn.
Duvelisib works in two ways: first by inhibiting two kinases
understood to help malignant B cells grow and survive, and then by disrupting
the microenvironment that supports tumor growth. “This dual inhibitory action
is likely what makes duvelisib effective for patients with CLL or SLL,” said
The multicenter, international DUO trial included 319
patients with relapsed or treatment-resistant CLL or SLL who had previously
received a median of two anti-cancer therapies (one-third had received three or
more). Patients were randomized to either receive twice-daily oral duvelisib or
intravenous ofatumumab, an approved monoclonal antibody that targets the CD20
protein on the surface of B cells. They were then followed for a median of 22.4
Overall response rate was also higher in the duvelisib group
(74 vs. 45 percent, respectively).
Median duration of treatment was 50 weeks for the duvelisib
group and 23 weeks for those receiving ofatumumab, allowing researchers to
collect more data on side effects. The most common adverse events were
diarrhea, nausea, pyrexia, neutropenia, anemia, and cough in the duvelisib
group and neutropenia and infusion reactions in the ofatumumab arm.
Most people taking duvelisib (78 percent) also had
meaningful reductions in their lymph nodes compared with 16 percent of patients
receiving ofatumumab. Swollen lymph nodes in the neck, arms, and abdomen can
lead to limited mobility and increased discomfort.
According to the National Cancer Institute, more than 20,000
new cases of CLL are diagnosed in the US every year, with 4,600 related death
“For people who face aggressive CLL, there is a continuing
need for new advancements and therapies,” said Dr. Flinn. “Through continued
research for targeted treatments, we have seen improved response rates and
progression-free survival, easing symptoms, and improvements in patients’
quality of life.”
On Sept. 24, 2018, the U. S. Food and Drug Administration
granted regular approval to duvelisib for adult patients with relapsed or
refractory CLL or SLL after at least two prior therapies.
The DUO Trial was
sponsored by Verastem Oncology and Infinity Pharmaceuticals, Inc.
the most cited peer-reviewed publication in the field of hematology, is
available weekly in print and online. Blood is a journal of the American
Society of Hematology (ASH) (www.hematology.org),
the world’s largest professional society concerned with the causes and
treatment of blood disorders.
ASH’s mission is to further the understanding, diagnosis,
treatment, and prevention of disorders affecting blood, bone marrow, and the
immunologic, hemostatic, and vascular systems by promoting research, clinical
care, education, training, and advocacy in hematology.
blood® is a registered trademark of the American Society of
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