-- Sub-Population Analysis Demonstrates High
Rates of Durable Response and Overall Survival Regardless of Age at
Two Years Post-Treatment --
-- Safety Management Study Shows Early Use
of Steroids May Help Manage Severe Cytokine Release Syndrome and
Neurologic Events without Effect on Response Rates --
Kite, a Gilead Company (Nasdaq: GILD), today announced
findings from two new analyses from the ZUMA-1 trial of Yescarta®
(axicabtagene ciloleucel) in adult patients with relapsed or
refractory large B-cell lymphoma. These results include a two-year
sub-population analysis of efficacy and safety in ZUMA-1 patients
(registrational Cohorts 1 and 2) by age, as well as preliminary
data from a separate safety management study of patients receiving
early steroid intervention for cytokine release syndrome (CRS) and
neurologic events. The results were presented today at the 2019
American Society of Clinical Oncology (ASCO) Annual Meeting May 31
– June 4, in Chicago.
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“Longer-term data from ZUMA-1 have shown more than half of
patients were still alive two years after treatment with Yescarta,”
said John McHutchison, AO, MD, Chief Scientific Officer and Head of
Research and Development, Gilead Sciences. “We are committed to
further defining the clinical profile of Yescarta, including
evaluation of new safety management protocols to further enhance
patient care and help move the cell therapy field forward.”
Yescarta was the first CAR T cell therapy approved by the U.S.
Food and Drug Administration (FDA) for the treatment of adult
patients with relapsed or refractory large B-cell lymphoma after
two or more lines of systemic therapy, including diffuse large
B-cell lymphoma (DLBCL) not otherwise specified, primary
mediastinal large B-cell lymphoma, high grade B-cell lymphoma and
DLBCL arising from follicular lymphoma. Yescarta is not indicated
for the treatment of patients with primary central nervous system
lymphoma. The Yescarta U.S. Prescribing Information has a BOXED
WARNING for the risks of CRS and neurologic toxicities; see below
for Important Safety Information.
Two-Year Analysis of ZUMA-1 by Age Supports Clinical Benefit
of Yescarta in Patients 65 and Older (Abstract #7555)
Patients with relapsed large B-cell lymphoma in the two-year
follow-up of ZUMA-1 were analyzed in two groups – those 65 years or
older (≥65) (n=24) and those younger than 65 years (<65) (n=77).
With a median follow-up of 27.1 months, the objective response rate
(ORR) per investigator assessment was 92 percent among ≥65 patients
and 81 percent in the <65 group, with 75 percent and 53 percent
of patients in the respective groups achieving a complete response.
At two years, 42 percent of ≥65 patients and 38 percent of <65
patients were in an ongoing response. The 24-month overall survival
rate was 54 percent and 49 percent in each respective group. Among
all patients in the safety analysis (27 patients ≥65 and 81
patients <65), most (98 percent) experienced Grade ≥3 adverse
events. Grade ≥3 neurologic events occurred in 12 patients ≥65 (44
percent) and in 23 patients <65 (28 percent). Grade ≥3 CRS
occurred in 2 patients ≥65 (7 percent) and in 10 patients <65
(12 percent).
“Patients with refractory large B-cell lymphoma who have
exhausted treatment options and are still facing progressive
disease are often older,” said Sattva S. Neelapu, MD, ZUMA-1
co-lead investigator and Professor, Department of Lymphoma/Myeloma,
Division of Cancer Medicine at The University of Texas MD Anderson
Cancer Center. “Our results showed axicabtagene ciloleucel offered
clinical benefit with a manageable safety profile in people aged 65
and over, which reinforces this therapy’s use in these patients who
otherwise have limited treatment options.”
Preliminary Results Expand Understanding of CAR T Safety
Profile (Abstract #7558)
Kite is currently conducting various studies to further evaluate
the efficacy and safety profile of Yescarta, including clinical
trials evaluating use of bridging chemotherapy and other
combination approaches.
In a ZUMA-1 safety management study (Cohort 4), patients with
relapsed or refractory large B-cell lymphoma treated with Yescarta
received earlier steroid intervention beginning when patients
experienced Grade 1 neurologic events and at Grade 1 CRS when no
improvement was observed after three days of supportive care.
As of the abstract data cut-off, 21 of 40 planned patients had
received Yescarta, with a median follow-up of 7.7 months; 76
percent of patients received corticosteroids and 86 percent
received tocilizumab. Grade ≥3 adverse events occurred in 95
percent of patients; Grade ≥3 events included decreased neutrophil
count (33 percent) and anemia (24 percent). Grade 1 or 2 neurologic
events and CRS occurred in 48 percent and 100 percent of patients,
respectively. No patients experienced Grade ≥3 CRS, and Grade ≥3
neurologic events occurred in only 10 percent of patients, both
numerically lower than in the registrational cohorts of ZUMA-1.
There were no deaths due to adverse events in Cohort 4.
ORR per investigator assessment was 81 percent in the cohort,
and 62 percent of patients achieved a complete response. The median
duration of response has not yet been reached.
“Preliminary results of the ZUMA-1 expansion cohort suggest
early steroid interventions may reduce the incidence of severe CRS
and neurologic events associated with Yescarta without impacting
the high response rates to Yescarta therapy in relapsed or
refractory large B-cell lymphoma,” said Max S. Topp, MD, ZUMA-1
cohort 4 lead investigator and Professor and Head of Hematology,
University Hospital of Wuerzburg, Germany. “While longer follow-up
in a greater number of patients is required, response rates thus
far have been comparable to the pivotal ZUMA-1 study cohorts and
rates of Grade 3 or higher CRS and neurologic events have been
lower in this preliminary analysis, suggesting that early adverse
event management with steroids may further improve the benefit/risk
profile of CAR T therapy.”
U.S. Important Safety Information for
Yescarta
BOXED WARNING: CYTOKINE RELEASE SYNDROME AND
NEUROLOGIC TOXICITIES
- Cytokine Release Syndrome (CRS),
including fatal or life-threatening reactions, occurred in patients
receiving Yescarta. Do not administer Yescarta to patients with
active infection or inflammatory disorders. Treat severe or
life-threatening CRS with tocilizumab or tocilizumab and
corticosteroids.
- Neurologic toxicities, including
fatal or life-threatening reactions, occurred in patients receiving
Yescarta, including concurrently with CRS or after CRS resolution.
Monitor for neurologic toxicities after treatment with Yescarta.
Provide supportive care and/or corticosteroids as needed.
- Yescarta is available only through a
restricted program under a Risk Evaluation and Mitigation Strategy
(REMS) called the Yescarta REMS.
CYTOKINE RELEASE SYNDROME (CRS): CRS occurred in 94% of
patients, including 13% with ≥ Grade 3. Among patients who died
after receiving Yescarta, 4 had ongoing CRS at death. The median
time to onset was 2 days (range: 1-12 days) and median duration was
7 days (range: 2-58 days). Key manifestations include fever (78%),
hypotension (41%), tachycardia (28%), hypoxia (22%), and chills
(20%). Serious events that may be associated with CRS include
cardiac arrhythmias (including atrial fibrillation and ventricular
tachycardia), cardiac arrest, cardiac failure, renal insufficiency,
capillary leak syndrome, hypotension, hypoxia, and hemophagocytic
lymphohistiocytosis/macrophage activation syndrome. Ensure that 2
doses of tocilizumab are available prior to infusion of Yescarta.
Monitor patients at least daily for 7 days at the certified
healthcare facility following infusion for signs and symptoms of
CRS. Monitor patients for signs or symptoms of CRS for 4 weeks
after infusion. Counsel patients to seek immediate medical
attention should signs or symptoms of CRS occur at any time. At the
first sign of CRS, institute treatment with supportive care,
tocilizumab or tocilizumab and corticosteroids as indicated.
NEUROLOGIC TOXICITIES: Neurologic toxicities occurred in
87% of patients. Ninety-eight percent of all neurologic toxicities
occurred within the first 8 weeks, with a median time to onset of 4
days (range: 1-43 days) and a median duration of 17 days. Grade 3
or higher occurred in 31% of patients. The most common neurologic
toxicities included encephalopathy (57%), headache (44%), tremor
(31%), dizziness (21%), aphasia (18%), delirium (17%), insomnia
(9%) and anxiety (9%). Prolonged encephalopathy lasting up to 173
days was noted. Serious events including leukoencephalopathy and
seizures occurred with Yescarta. Fatal and serious cases of
cerebral edema have occurred in patients treated with
Yescarta. Monitor patients at least daily for 7 days at the
certified healthcare facility following infusion for signs and
symptoms of neurologic toxicities. Monitor patients for signs or
symptoms of neurologic toxicities for 4 weeks after infusion and
treat promptly.
YESCARTA REMS: Because of the risk of CRS and neurologic
toxicities, Yescarta is available only through a restricted program
under a Risk Evaluation and Mitigation Strategy (REMS) called the
Yescarta REMS. The required components of the Yescarta REMS are:
Healthcare facilities that dispense and administer Yescarta must be
enrolled and comply with the REMS requirements. Certified
healthcare facilities must have on-site, immediate access to
tocilizumab, and ensure that a minimum of 2 doses of tocilizumab
are available for each patient for infusion within 2 hours after
Yescarta infusion, if needed for treatment of CRS. Certified
healthcare facilities must ensure that healthcare providers who
prescribe, dispense or administer Yescarta are trained about the
management of CRS and neurologic toxicities. Further information is
available at www.YESCARTAREMS.com or 1-844-454-KITE (5483).
HYPERSENSITIVITY REACTIONS: Allergic reactions may occur.
Serious hypersensitivity reactions including anaphylaxis may be due
to dimethyl sulfoxide (DMSO) or residual gentamicin in
Yescarta.
SERIOUS INFECTIONS: Severe or life-threatening infections
occurred. Infections (all grades) occurred in 38% of patients, and
in 23% with ≥ Grade 3. Grade 3 or higher infections with an
unspecified pathogen occurred in 16% of patients, bacterial
infections in 9%, and viral infections in 4%. Yescarta should not
be administered to patients with clinically significant active
systemic infections. Monitor patients for signs and symptoms of
infection before and after Yescarta infusion and treat
appropriately. Administer prophylactic anti-microbials according to
local guidelines. Febrile neutropenia was observed in 36% of
patients and may be concurrent with CRS. In the event of febrile
neutropenia, evaluate for infection and manage with broad spectrum
antibiotics, fluids and other supportive care as medically
indicated. Hepatitis B virus (HBV) reactivation, in some cases
resulting in fulminant hepatitis, hepatic failure and death, can
occur in patients treated with drugs directed against B cells.
Perform screening for HBV, HCV, and HIV in accordance with clinical
guidelines before collection of cells for manufacturing.
PROLONGED CYTOPENIAS: Patients may exhibit cytopenias for
several weeks following lymphodepleting chemotherapy and Yescarta
infusion. Grade 3 or higher cytopenias not resolved by Day 30
following Yescarta infusion occurred in 28% of patients and
included thrombocytopenia (18%), neutropenia (15%), and anemia
(3%). Monitor blood counts after Yescarta infusion.
HYPOGAMMAGLOBULINEMIA: B-cell aplasia and
hypogammaglobulinemia can occur. Hypogammaglobulinemia occurred in
15% of patients. Monitor immunoglobulin levels after treatment and
manage using infection precautions, antibiotic prophylaxis and
immunoglobulin replacement. The safety of immunization with live
viral vaccines during or following Yescarta treatment has not been
studied. Vaccination with live virus vaccines is not recommended
for at least 6 weeks prior to the start of lymphodepleting
chemotherapy, during Yescarta treatment, and until immune recovery
following treatment.
SECONDARY MALIGNANCIES: Patients may develop secondary
malignancies. Monitor life-long for secondary malignancies. In the
event that a secondary malignancy occurs, contact Kite at
1-844-454-KITE (5483) to obtain instructions on patient samples to
collect for testing.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: Due to the
potential for neurologic events, including altered mental status or
seizures, patients are at risk for altered or decreased
consciousness or coordination in the 8 weeks following Yescarta
infusion. Advise patients to refrain from driving and engaging in
hazardous occupations or activities, such as operating heavy or
potentially dangerous machinery, during this initial period.
ADVERSE REACTIONS: The most common adverse reactions
(incidence ≥ 20%) include CRS, fever, hypotension, encephalopathy,
tachycardia, fatigue, headache, decreased appetite, chills,
diarrhea, febrile neutropenia, infections-pathogen unspecified,
nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation,
and cardiac arrhythmias.
About Kite
Kite, a Gilead Company, is a biopharmaceutical company based in
Santa Monica, California. Kite is engaged in the development of
innovative cancer immunotherapies. The company is focused on
chimeric antigen receptor and T cell receptor engineered cell
therapies. For more information on Kite, please visit
www.kitepharma.com.
About Gilead Sciences
Gilead Sciences, Inc. is a research-based biopharmaceutical
company that discovers, develops and commercializes innovative
medicines in areas of unmet medical need. The company strives to
transform and simplify care for people with life-threatening
illnesses around the world. Gilead has operations in more than 35
countries worldwide, with headquarters in Foster City,
California. For more information on Gilead Sciences, please visit
the company’s website at www.gilead.com.
Forward-Looking
Statement
This press release includes forward-looking statements, within
the meaning of the Private Securities Litigation Reform Act of 1995
that are subject to risks, uncertainties and other factors,
including Kite’s ability to complete the ZUMA-1 trial of Yescarta
in adult patients with relapsed or refractory large B-cell lymphoma
in the currently anticipated timelines, or at all. In addition,
there is the possibility of unfavorable results from other ongoing
and additional clinical trials involving Yescarta. All statements
other than statements of historical fact are statements that could
be deemed forward-looking statements. These risks, uncertainties
and other factors could cause actual results to differ materially
from those referred to in the forward-looking statements. The
reader is cautioned not to rely on these forward-looking
statements. These and other risks are described in detail in
Gilead’s Quarterly Report on Form 10-Q for the quarter ended March
31, 2019, as filed with the U.S. Securities and Exchange
Commission. All forward-looking statements are based on information
currently available to Gilead and Kite, and Gilead and Kite assume
no obligation to update any such forward-looking statements.
U.S. Prescribing Information for Yescarta,
including BOXED WARNING, is available at www.kitepharma.com
and www.gilead.com.
Yescarta is a registered trademark
of Gilead Sciences, Inc., or its related companies.
For more information on Kite, please visit the
company’s website at www.kitepharma.com. Learn more about
Gilead at www.gilead.com, follow Gilead on Twitter
(@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5
or 1-650-574-3000.
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