First Multicenter Trial Finds CAR T-Cell Immunotherapy Effective, Feasible for Hard-to-Treat Lymphoma
Interim analysis shows nearly six-fold
higher rate of complete remission for refractory non-Hodgkin lymphoma with
KTE-C19 compared to historical data
Published on: December 06, 2016
(San Diego, December 6,
2016) – A late-breaking abstract being presented today during
the 58th American Society of Hematology (ASH) Annual Meeting and Exposition in
San Diego demonstrates that chimeric antigen receptor (CAR) T-cell therapy is a
promising option for treating refractory non-Hodgkin lymphoma and practical to
implement in a variety of real-world clinical settings. The study, which
involved 22 institutions and tested a product called KTE-C19 (anti-CD19 CAR),
is the first multicenter trial of this cellular immunotherapy-based treatment
approach for lymphoma.
The study focuses on
patients with aggressive non-Hodgkin lymphoma that does not respond to
chemotherapy or recurs after autologous stem cell transplant. Such
chemorefractory patients have a poor prognosis; median overall survival is just
over six months and only about eight percent achieve complete cancer remission
with existing therapies. The experimental therapy, KTE-C19, is designed to
equip a patient’s own immune cells with weapons to find and destroy cancer
aggressive non-Hodgkin lymphoma have a major unmet need in terms of available
therapies that can induce long-term remission, and there really has been no new
treatment for these patients for over 20 years,” said lead study author Sattva
S. Neelapu, MD, of The University of Texas MD Anderson Cancer Center in Houston.
“KTE-C19 could potentially be the solution to that need, and the hope is that this
treatment option could be curative for some of these patients.”
He said the study,
called ZUMA-1, bolsters evidence from previous trials that reported sustained
remission after CAR T-cell therapy with KTE-C19, a treatment in which doctors
extract T cells from a patient, genetically engineer the cells with CD19
receptors to seek out cancer cells, expand the population of the engineered
cells, and then infuse them back into the patient. In the first phase of
ZUMA-1, which was conducted in four institutions, 43 percent of patients have
ongoing complete remission at 12 months.
To test the
treatment’s real-world feasibility, the second phase of ZUMA-1 expanded the
study to involve 22 institutions, most of which had no prior experience with
CAR T-cell therapy. The new findings report positive results from a
pre-specified interim analysis of 51 patients with diffuse large B-cell
lymphoma (DLBCL), a common and aggressive form of non-Hodgkin lymphoma. Following
KTE-C19 treatment, these patients had an overall response rate of 76 percent (47%
complete remission and 29% partial remission) with most responses noted within
the first month. As in previous studies, some patients’ cancers rebounded after
the first few months; by the end of month three, the overall remission rate was
39 percent (33% complete remission and 6% partial remission).
Researchers said the
results are encouraging from an efficacy standpoint and also show that CAR
T-cell manufacturing, treatment logistics, and the management of adverse events
can be successfully implemented across multiple sites. “Efficacy often tends to
be lower when you apply a new treatment at multiple centers,” said Dr. Neelapu.
“It was very gratifying to see that efficacy and side effects are similar to
what was observed in previous single-institution studies.”
events reported in the total DLBCL cohort of 73 patients that were related to
KTE-C19 included neurologic events (25% of patients; typically temporary
confusion or disorientation) and grade three or higher cytokine release
syndrome, a common, potentially dangerous reaction to this type of infusion (14%
of patients). The most common symptoms of cytokine release syndrome were fever,
drop in blood pressure, and shortness of breath, according to Dr. Neelapu. Researchers
report one patient died as a result of over-activation of the immune system.
Recent studies of CAR
T-cell therapy have improved the ability to manage side effects, researchers
said. “We now have guidelines on how to recognize and grade these side effects
and how to manage the symptoms, and we were able to implement those across
multiple institutions with no prior experience with CAR T-cell therapy,” said Dr.
Neelapu. “I think it has become much more manageable and safer now.”
The team has also separately
analyzed results from 20 patients in ZUMA-1’s second cohort (abstract #998), which include patients with
primary mediastinal B-cell lymphoma or transformed follicular lymphoma, two
tumor types that are less common than DLBCL. The overall response rate in this
second cohort is 80 percent with a complete remission rate of 55 percent. The
researchers will continue to track patient outcomes in these cohorts for 15
study was funded by Kite Pharma, Inc., which makes KTE-C19 and partially
supported by The Leukemia & Lymphoma Society Therapy Acceleration Program®.
Sattva S. Neelapu, MD, The
University of Texas MD Anderson Cancer Center, Houston, Texas, will present
this study, titled “Kte-C19 (anti-CD19
CAR T Cells) Induces Complete Remissions in Patients with Refractory Diffuse
Large B-Cell Lymphoma (DLBCL): Results from the Pivotal Phase 2 Zuma-1,”
(LBA-6) during the late-breaking abstracts session on Tuesday, December 6 at
7:30 a.m. PST in Hall AB.
For the complete
annual meeting program and abstracts, visit www.hematology.org/annual-meeting.
Follow @ASH_hematology and #ASH16 on Twitter and like ASH on Facebook for the
most up-to-date information about the 2016 ASH Annual Meeting.
The American Society
of Hematology (ASH) (www.hematology.org) is the world's largest professional
society of hematologists dedicated to furthering the understanding, diagnosis,
treatment, and prevention of disorders affecting the blood. For more than 50
years, the Society has led the development of hematology as a discipline by
promoting research, patient care, education, training, and advocacy in
hematology. The official journal of ASH is Blood
(www.bloodjournal.org), the most cited peer-reviewed publication in the
field, as well as the newly launched, online, open-access journal, Blood Advances (www.bloodadvances.org).
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