On Location
Early-Phase Trial Suggests
CAR T-Cell Therapy Safe for
Patients with Non-Hodgkin
Lymphoma
Results from the phase I ZUMA1 trial presented at the AACR
Annual Meeting suggest that
KTE-C19, a chimeric antigen receptor (CAR), is a safe treatment
option for patients with nonHodgkin lymphoma (NHL).
“Anti-CD19 CAR T cells with
CD3 zeta and CD28 signaling domains showed durable remissions
in subjects with relapsed/refractory advanced B-cell malignancies
as the best response to last line
of therapy)
• Disease progression within
12 months post-autologous
hematopoietic cell
transplantation
After a median follow-up of 13
weeks post-KTE-C19 infusion, all
patients were evaluable for safety
and six were evaluable for efficacy.
“In ZUMA-1, the KTE-C19
regimen was safe for further
study [in patients with nonHodgkin lymphoma].”
—ARMIN GHOBADI, MD
[in an earlier National Cancer
Institute trial],” the study authors,
led by Armin Ghobadi, MD, from
the Siteman Cancer Center at the
Washington University School of
Medicine in St. Louis, Missouri,
explained. “KTE-C19 uses the
same CAR construct as investigated in the NCI study in a six- to
eight-day manufacturing process.”
The updated results of the
ZUMA-1 trials presented by Dr.
Ghobadi and colleagues include
data from seven adult patients (enrolled as of November 20, 2015)
with diffuse large B-cell lymphoma
who received KTE-C19 at a dose
of 2x106 anti-CD19 CAR T cells/
kg, after a fixed-dose conditioning
chemotherapy regimen consisting
of cyclophosphamide and fludarabine. The study’s primary endpoint
was safety (determined by the incidence of dose-limiting toxicities),
and secondary endpoints included
overall response rate, duration of
response, and biomarkers.
Patients were eligible for
inclusion if they had:
• An Eastern Cooperative
Oncology Group score 0-1
• Chemotherapy-refractory
disease (defined as progressive
disease or stable disease [SD]
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ASH Clinical News
The most commonly reported
toxicities included cytokine
release syndrome (CRS) and
neurotoxicity, which were generally reversible and managed with
supportive care, α-IL6R, and steroids. One patient experienced
a dose-limiting toxicity of grade
4 encephalopathy and grade 4
CRS; this patient later died due
to an intracranial hemorrhage
deemed unrelated to KTE-C19
treatment (per the investigator).
“The KTE-C19 regimen was
safe for further study,” Dr. Ghobadi and colleagues concluded.
Five of the seven patients
(71%) responded to treatment:
four complete responses, one partial response, one case of stable
disease, and one response that
was not evaluable. CAR T cells
peaked within two weeks of treatment and were detectable one to
three months post-infusion.
These preliminary results in this
small population are being further
confirmed in a “potentially pivotal”
phase II portion of ZUMA-1, which
is ongoing, the authors noted.
REFERENCE
Ghobadi A, Locke FL, Neelapu SS, et al. Updated phase I results
from ZUA-1: A phase I-II multicenter study evaluating the safety
and efficacy of KTE-C19 (anti-CD19 CAR T cells) in subjects with
refractory aggressive non-Hodgkin lymphoma (NHL). Abstract
CT135. Presented at the AACR Annual Meeting, April 19, 2016;
New Orleans, LA.
Novel Combination
Therapy Targets Cancer
Stem Cells in Multiple
Myeloma
Cancer stem cells (CSCs) have been identified in many
diseases, including multiple myeloma (MM), but it is
unclear how their frequencies change during treatment
with either standard or CSC-targeting treatments. According to a study of 17 patients with newly diagnosed
MM presented at the AACR Annual Meeting, the novel
anti-CD19 monoclonal antibody MEDI-551, in combination with standard lenalidomide and dexamethasone
(Rd), was well tolerated and decreased the frequencies
of CSCs. Results from the single-arm trials also suggested that prolonged treatment with MEDI-551 was
safe and had clinically benefit.
MEDI-551 works by targeting CD19, and, the study
authors, led by Carol Ann Huff, MD, from Johns Hopkins University School of Medicine in Baltimore, Maryland, explained, “In multiple myeloma, CSCs can express
B-cell surface antigens, including CD19.”
The patients had a median age of 65 years (range =
34-73 years). Two patients did not receive MEDI-551 due
to progressive disease (PD) and non-compliance, leaving
15 evaluable patients.
Patients enrolled in the trial received two initial 28-day
cycles of Rd: lenalidomide 25 mg administered orally twice
daily on days one through 21 and dexamethasone 40 mg
administered orally twice daily once per week. Following
these two cycles, MEDI-551, at 4 mg/kg, was administered
intravenously on days one through eight of cycle three and
day one of cycle four. Patients who responded to this treatment then continued on Rd therapy.
The researchers serially measured myeloma CSCs
by quantifying the growth of colony-forming units of
MM (CFU-MM) from marrow aspirates at baseline, the
end of cycle 2 (Rd alone), and the end of cycle 4 (Rd +
MEDI-551).
Peripheral blood CSCs were quantified by flow cytometry at baseline and at the end of cycles two, four, five,
and seven. Clinical response and toxicity were assessed
according to the International Myeloma Working Group
June 2016