– ZUMA-1 Post-Hoc Analysis Shows Five-Year
Lymphoma-Related Event-Free Survival in a Substantial Proportion of
Patients with Refractory Large B-cell Lymphoma –
– Four-Year Follow-up from ZUMA-5
Demonstrates Continued Durable Response and Long-Term Survival in
Patients with Relapsed/Refractory Follicular Lymphoma –
– ZUMA-7 Overall Survival Subgroup Analysis
in Patients Aged 65+ Shows that Age Alone is not a Barrier to
Receiving CAR T –
Kite, a Gilead Company (Nasdaq: GILD), today announced data from
follow-up analyses of three studies of Yescarta® (axicabtagene
ciloleucel) that demonstrate the long-term survival potential for
patients living with several sub-types of relapsed or refractory
(R/R) non-Hodgkin lymphoma, which were presented at the 65th
American Society of Hematology (ASH) Annual Meeting &
Exposition. This included ZUMA-1 (Abstract #4864) showing that
patients with refractory large B-cell lymphoma (LBCL) who
maintained a complete response (CR) at 12- and 24-months following
treatment with Yescarta had a 72-month estimated disease-specific
survival (DSS) of 94.4% and 100%, respectively. Long-term data from
the ZUMA-5 (Abstract #4868) and ZUMA-7 (Abstract #1761) studies
were also presented.
“As we continue to follow up with patients living with
difficult-to-treat types of lymphomas, we are witnessing a pattern
of longer-term survival with a one-time treatment with Yescarta,”
said Frank Neumann, MD, PhD, Senior Vice President, Global Head of
Clinical Development, Kite. “The results of these studies, coupled
with our rapid and reliable manufacturing, add to our body of
knowledge on the benefits and utility of Yescarta as a treatment
with curative intent, changing the way these cancers are treated
and providing hope to thousands of lymphoma patients.”
Detailed Information on Yescarta Abstracts:
Abstract #4864 Curative Potential of Axicabtagene
Ciloleucel (Axi-Cel): an Exploratory Long-Term Survival Assessment
in Patients with Refractory Large B-Cell Lymphoma from ZUMA-1
ZUMA-1 is an ongoing, multicenter, single-arm, open-label Phase
1/2 trial evaluating the safety and efficacy of Yescarta CAR T-cell
therapy in adult patients with refractory LBCL. In this post hoc
analysis of ZUMA-1, with up to six years of follow-up, the
five-year long-term lymphoma-related event-free survival (LREFS)
was used as a measure to explore Yescarta’s curative potential.
Yescarta had long-term LREFS in a substantial proportion of
patients, with a five-year rate of 34% (57% among patients who
achieved a CR). Additionally, this exploratory analysis found that,
at six years, median overall survival (OS) remained consistent with
prior analyses at 25.8 months (95% Confidence Interval [CI],
12.8-63.7) and patients who had a CR at 12 and 24 months had a
72-month DSS of 94.4% and 100%, respectively, which may be
predictive of extended OS. Among patients who had a CR to therapy,
the leading risks of death were reasons other than progression or
adverse events after month 24 post-infusion.
Abstract #4868 Axicabtagene Ciloleucel (Axi-Cel) in
Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma:
4-Year Follow-Up from the Phase 2 ZUMA-5 Trial
ZUMA-5 is an ongoing, single-arm, open-label, international,
multicenter Phase 2 trial evaluating 122 adult patients with R/R
indolent non-Hodgkin lymphoma (iNHL; follicular lymphoma [FL] and
marginal zone lymphoma [MZL]). In this study, at a median follow-up
of 52.5 months (range, 20.3-69.4; FL: 53.7, MZL: 43.8), the overall
response rate (ORR) remained consistent with prior analyses (90%
ORR, 75% CR rate) and the median duration of response (DOR) was
55.5 months (95% CI, 38.6-not estimable [NE]; FL: 55.5, MZL: not
reached). At data cutoff, four years of follow-up, median
progression free survival (PFS) was 57.3 months (95% CI, 34.9-NE;
FL: 57.3, MZL: 46.9) and the 48-month OS rate was 72% (FL: 72%,
MZL: 68%). No new neurologic events, hypogammaglobulinemia cases,
Grade ≥3 cytopenias or Grade ≥3 infections occurred in the
four-year analysis compared to the three-year analysis.
“Taken together with other studies, the results we saw in our
four-year analysis from the ZUMA-5 trial and up to six years of
follow-up from the ZUMA-1 trial support the durability and safety
of axi-cel in patients with follicular lymphoma and large B-cell
lymphoma who have progressed following previous lines of therapy,”
said Dr. Sattva S. Neelapu, The University of Texas MD Anderson
Cancer Center. “We are encouraged by these data, particularly the
continued durable response and long-term survival in these patient
populations that speak to the potentially curative benefit of this
therapy. As we continue to follow these patients, our hope is that
these positive survival trends are sustained.”
Abstract #1761 Improved Overall Survival With
Axicabtagene Ciloleucel vs Standard of Care in Second-Line Large
B-Cell Lymphoma Among the Elderly: A Subgroup Analysis of
ZUMA-7
ZUMA-7 is a randomized, open-label, global, multicenter, Phase 3
trial evaluating the safety and efficacy of Yescarta versus
standard of care (SOC; [chemoimmunotherapy followed by HDT-ASCT in
patients who had a response]) for treatment of adult patients with
refractory LBCL or relapse within 12 months of first-line therapy.
In this analysis, investigators reported updated efficacy and
safety results from the primary OS analysis among ZUMA-7 patients
aged ≥65 years and ≥70 years. At a median follow-up of 46.6 months,
OS was prolonged in the Yescarta vs. SOC arm in patients aged ≥65
years (HR, 0.691; 95% CI, 0.401-1.190) and for those ≥70 y (HR,
0.330; 95% CI, 0.135-0.809). PFS assessed by investigator confirmed
benefit of Yescarta over SOC in patients aged ≥65 years (HR, 0.406;
95% CI, 0.230‑0.715) and in patients aged ≥70 years (HR, 0.206; 95%
CI, 0.078‑0.547). No new treatment-related deaths occurred since
the primary event-free survival (EFS) analysis for ZUMA-7.
Yescarta Age 65+
SOC Age 65+
Yescarta Age 70+
SOC Age 70+
Median OS (months)
43.5 (95% CI, 20.9-NE)
19.5 (95% CI, 12.3-NE)
24.7 (95% CI, 12.8-NE)
11.2 (95% CI, 6.1-NE)
Median PFS (months)
28.6 (95% CI, 5.1-NE)
5.0 (95% CI, 2.8-7.3)
11.4 (95% CI, 4.1-NE)
2.7 (95% CI, 1.7-5.0)
“Traditionally, older patients with relapsed/refractory large
B-cell lymphoma have not been able to access some treatments due to
presumed concerns regarding increased toxicity related to their age
and comorbidities,” said Professor Marie José Kersten, Amsterdam
University Medical Centers. “However, what we’re seeing with this
subgroup analysis from the landmark ZUMA-7 trial, is that the data
clearly support the consideration of axi-cel also for older
patients with relapsed/refractory large B-cell lymphoma. As more
data become available, my hope is that patients can receive the
therapies that offer them the greatest chance for response and
prolonged survival, regardless of age.”
The Yescarta U.S. Prescribing Information has a BOXED WARNING
for the risks of CRS and neurologic toxicities, and Yescarta is
approved with a Risk Evaluation and Mitigation Strategy (REMS) due
to these risks; see below for Important Safety Information.
About Follicular
Lymphoma
FL is a form of iNHL in which malignant tumors slowly grow but
can become more aggressive over time.
FL is the most common form of indolent lymphoma and the second
most common type of lymphoma globally. It accounts for
approximately 22 percent of all lymphomas diagnosed worldwide.
Despite advances in management and substantial improvements in
long-term survival, patients living with FL have varied outcomes.
Currently, there are no standard of care treatments for relapsed
and refractory FL after two or more lines of therapy.
About Large B-Cell
Lymphoma
Globally, LBCL is the most common type of NHL. In the United
States, more than 18,000 people are diagnosed with LBCL each year.
About 30-40% of patients with LBCL will need second-line treatment,
as their cancer will either relapse (return) or become refractory
(not respond) to initial treatment.
About Yescarta
Please see full US Prescribing Information, including BOXED
WARNING and Medication Guide.
YESCARTA is a CD19-directed genetically modified autologous T
cell immunotherapy indicated for the treatment of:
- Adult patients with large B-cell lymphoma that is refractory to
first-line chemoimmunotherapy or that relapses within 12 months of
first-line chemoimmunotherapy.
- 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.
- Limitations of Use: YESCARTA is
not indicated for the treatment of patients with primary central
nervous system lymphoma.
- Adult patients with relapsed or refractory follicular lymphoma
(FL) after two or more lines of systemic therapy. This indication
is approved under accelerated approval based on the response rate.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in the
confirmatory trial(s).
U.S. IMPORTANT SAFETY INFORMATION
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 and TECARTUS REMS Program.
CYTOKINE RELEASE SYNDROME (CRS)
CRS, including fatal or life-threatening reactions, occurred.
CRS occurred in 90% (379/422) of patients with non-Hodgkin lymphoma
(NHL), including ≥ Grade 3 in 9%. CRS occurred in 93% (256/276) of
patients with large B-cell lymphoma (LBCL), including ≥ Grade 3 in
9%. Among patients with LBCL who died after receiving YESCARTA, 4
had ongoing CRS events at the time of death. For patients with LBCL
in ZUMA-1, the median time to onset of CRS was 2 days following
infusion (range: 1-12 days) and the median duration was 7 days
(range: 2-58 days). For patients with LBCL in ZUMA-7, the median
time to onset of CRS was 3 days following infusion (range: 1-10
days) and the median duration was 7 days (range: 2-43 days). CRS
occurred in 84% (123/146) of patients with indolent non-Hodgkin
lymphoma (iNHL) in ZUMA-5, including ≥ Grade 3 in 8%. Among
patients with iNHL who died after receiving YESCARTA, 1 patient had
an ongoing CRS event at the time of death. The median time to onset
of CRS was 4 days (range: 1-20 days) and the median duration was 6
days (range: 1-27 days) for patients with iNHL.
Key manifestations of CRS (≥ 10%) in all patients combined
included fever (85%), hypotension (40%), tachycardia (32%), chills
(22%), hypoxia (20%), headache (15%), and fatigue (12%). Serious
events that may be associated with CRS include cardiac arrhythmias
(including atrial fibrillation and ventricular tachycardia), renal
insufficiency, cardiac failure, respiratory failure, cardiac
arrest, capillary leak syndrome, multi-organ failure, and
hemophagocytic lymphohistiocytosis/macrophage activation
syndrome.
The impact of tocilizumab and/or corticosteroids on the
incidence and severity of CRS was assessed in 2 subsequent cohorts
of LBCL patients in ZUMA-1. Among patients who received tocilizumab
and/or corticosteroids for ongoing Grade 1 events, CRS occurred in
93% (38/41), including 2% (1/41) with Grade 3 CRS; no patients
experienced a Grade 4 or 5 event. The median time to onset of CRS
was 2 days (range: 1-8 days) and the median duration of CRS was 7
days (range: 2-16 days). Prophylactic treatment with
corticosteroids was administered to a cohort of 39 patients for 3
days beginning on the day of infusion of YESCARTA. Thirty-one of
the 39 patients (79%) developed CRS and were managed with
tocilizumab and/or therapeutic doses of corticosteroids with no
patients developing ≥ Grade 3 CRS. The median time to onset of CRS
was 5 days (range: 1-15 days) and the median duration of CRS was 4
days (range: 1-10 days). Although there is no known mechanistic
explanation, consider the risk and benefits of prophylactic
corticosteroids in the context of pre-existing comorbidities for
the individual patient and the potential for the risk of Grade 4
and prolonged neurologic toxicities.
Ensure that 2 doses of tocilizumab are available prior to
YESCARTA infusion. Monitor patients for signs and symptoms of CRS
at least daily for 7 days at the certified healthcare facility, and
for 4 weeks thereafter. 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 (including immune effector cell-associated
neurotoxicity syndrome) that were fatal or life-threatening
occurred. Neurologic toxicities occurred in 78% (330/422) of all
patients with NHL receiving YESCARTA, including ≥ Grade 3 in 25%.
Neurologic toxicities occurred in 87% (94/108) of patients with
LBCL in ZUMA-1, including ≥ Grade 3 in 31% and in 74% (124/168) of
patients in ZUMA-7 including ≥ Grade 3 in 25%. The median time to
onset was 4 days (range: 1-43 days) and the median duration was 17
days for patients with LBCL in ZUMA-1. The median time to onset for
neurologic toxicity was 5 days (range: 1- 133 days) and the median
duration was 15 days in patients with LBCL in ZUMA-7. Neurologic
toxicities occurred in 77% (112/146) of patients with iNHL,
including ≥ Grade 3 in 21%. The median time to onset was 6 days
(range: 1-79 days) and the median duration was 16 days.
Ninety-eight percent of all neurologic toxicities in patients with
LBCL and 99% of all neurologic toxicities in patients with iNHL
occurred within the first 8 weeks of YESCARTA infusion. Neurologic
toxicities occurred within the first 7 days of infusion for 87% of
affected patients with LBCL and 74% of affected patients with
iNHL.
The most common neurologic toxicities (≥ 10%) in all patients
combined included encephalopathy (50%), headache (43%), tremor
(29%), dizziness (21%), aphasia (17%), delirium (15%), and insomnia
(10%). Prolonged encephalopathy lasting up to 173 days was noted.
Serious events, including aphasia, leukoencephalopathy, dysarthria,
lethargy, and seizures occurred. Fatal and serious cases of
cerebral edema and encephalopathy, including late-onset
encephalopathy, have occurred.
The impact of tocilizumab and/or corticosteroids on the
incidence and severity of neurologic toxicities was assessed in 2
subsequent cohorts of LBCL patients in ZUMA-1. Among patients who
received corticosteroids at the onset of Grade 1 toxicities,
neurologic toxicities occurred in 78% (32/41), and 20% (8/41) had
Grade 3 neurologic toxicities; no patients experienced a Grade 4 or
5 event. The median time to onset of neurologic toxicities was 6
days (range: 1-93 days) with a median duration of 8 days (range:
1-144 days). Prophylactic treatment with corticosteroids was
administered to a cohort of 39 patients for 3 days beginning on the
day of infusion of YESCARTA. Of those patients, 85% (33/39)
developed neurologic toxicities, 8% (3/39) developed Grade 3, and
5% (2/39) developed Grade 4 neurologic toxicities. The median time
to onset of neurologic toxicities was 6 days (range: 1-274 days)
with a median duration of 12 days (range: 1-107 days). Prophylactic
corticosteroids for management of CRS and neurologic toxicities may
result in a higher grade of neurologic toxicities or prolongation
of neurologic toxicities, delay the onset of and decrease the
duration of CRS.
Monitor patients for signs and symptoms of neurologic toxicities
at least daily for 7 days at the certified healthcare facility, and
for 4 weeks thereafter, and treat promptly.
REMS
Because of the risk of CRS and neurologic toxicities, YESCARTA
is available only through a restricted program called the YESCARTA
and TECARTUS REMS Program which requires that: Healthcare
facilities that dispense and administer YESCARTA must be enrolled
and comply with the REMS requirements and must have on-site,
immediate access to a minimum of 2 doses of tocilizumab 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 in the management of CRS and
neurologic toxicities. Further information is available at
www.YescartaTecartusREMS.com or 1-844-454-KITE (5483).
HYPERSENSITIVITY REACTIONS
Allergic reactions, including serious hypersensitivity reactions
or anaphylaxis, may occur with the infusion of YESCARTA.
SERIOUS INFECTIONS
Severe or life-threatening infections occurred. Infections (all
grades) occurred in 45% of patients with NHL; ≥ Grade 3 infections
occurred in 17% of patients, including ≥ Grade 3 infections with an
unspecified pathogen in 12%, bacterial infections in 5%, viral
infections in 3%, and fungal infections in 1%. YESCARTA should not
be administered to patients with clinically significant active
systemic infections. Monitor patients for signs and symptoms of
infection before and after infusion and treat appropriately.
Administer prophylactic antimicrobials according to local
guidelines.
Febrile neutropenia was observed in 36% of all patients with NHL
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.
In immunosuppressed patients, including those who have received
YESCARTA, life-threatening and fatal opportunistic infections
including disseminated fungal infections (e.g., candida sepsis and
aspergillus infections) and viral reactivation (e.g., human herpes
virus-6 [HHV-6] encephalitis and JC virus progressive multifocal
leukoencephalopathy [PML]) have been reported. The possibility of
HHV-6 encephalitis and PML should be considered in immunosuppressed
patients with neurologic events and appropriate diagnostic
evaluations should be performed.
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, including
YESCARTA. 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
cytopenias not resolved by Day 30 following YESCARTA infusion
occurred in 39% of all patients with NHL and included neutropenia
(33%), thrombocytopenia (13%), and anemia (8%). Monitor blood
counts after infusion.
HYPOGAMMAGLOBULINEMIA
B-cell aplasia and hypogammaglobulinemia can occur.
Hypogammaglobulinemia was reported as an adverse reaction in 14% of
all patients with NHL. 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
Secondary malignancies may develop. Monitor life-long for
secondary malignancies. In the event that one 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 non-laboratory adverse reactions (incidence ≥
20%) in patients with LBCL in ZUMA-7 included fever, CRS, fatigue,
hypotension, encephalopathy, tachycardia, diarrhea, headache,
musculoskeletal pain, nausea, febrile neutropenia, chills, cough,
infection with an unspecified pathogen, dizziness, tremor,
decreased appetite, edema, hypoxia, abdominal pain, aphasia,
constipation, and vomiting.
The most common adverse reactions (incidence ≥ 20%) in patients
with LBCL in ZUMA-1 included CRS, fever, hypotension,
encephalopathy, tachycardia, fatigue, headache, decreased appetite,
chills, diarrhea, febrile neutropenia, infections with an
unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness,
constipation, and cardiac arrhythmias.
The most common non-laboratory adverse reactions (incidence ≥
20%) in patients with iNHL in ZUMA-5 included fever, CRS,
hypotension, encephalopathy, fatigue, headache, infections with an
unspecified, tachycardia, febrile neutropenia, musculoskeletal
pain, nausea, tremor, chills, diarrhea, constipation, decreased
appetite, cough, vomiting, hypoxia, arrhythmia, and dizziness.
About Kite
Kite, a Gilead Company, is a global biopharmaceutical company
based in Santa Monica, California, focused on cell therapy to treat
and potentially cure cancer. As the global cell therapy leader,
Kite has treated more patients with CAR T-cell therapy than any
other company. Kite has the largest in-house cell therapy
manufacturing network in the world, spanning process development,
vector manufacturing, clinical trial production, and commercial
product manufacturing.
About Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has
pursued and achieved breakthroughs in medicine for more than three
decades, with the goal of creating a healthier world for all
people. The company is committed to advancing innovative medicines
to prevent and treat life-threatening diseases, including HIV,
viral hepatitis and cancer. Gilead operates in more than 35
countries worldwide, with headquarters in Foster City,
California.
Forward-Looking
Statements
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 the ability of Gilead and Kite to initiate, progress or
complete clinical trials within currently anticipated timelines or
at all, and the possibility of unfavorable results from ongoing or
additional clinical studies, including those involving Yescarta;
the possibility that Gilead and Kite may make a strategic decision
to discontinue development of programs for indications that are
currently under evaluation and, as a result, these programs may
never be successfully commercialized for such indications; the risk
that physicians may not see the benefits of prescribing Yescarta;
and any assumptions underlying any of the foregoing. These and
other risks, uncertainties and factors are described in detail in
Gilead’s Quarterly Report on Form 10-Q for the quarter ended
September 30, 2023, as filed with the U.S. Securities and Exchange
Commission. These risks, uncertainties and other factors could
cause actual results to differ materially from those referred to in
the forward-looking statements. All statements other than
statements of historical fact are statements that could be deemed
forward-looking statements. The reader is cautioned that any such
forward-looking statements are not guarantees of future performance
and involve risks and uncertainties, and is cautioned not to place
undue reliance on these forward-looking statements. All
forward-looking statements are based on information currently
available to Gilead and Kite, and Gilead and Kite assume no
obligation and disclaim any intent to update any such
forward-looking statements.
Kite, the Kite logo, Yescarta, and GILEAD are
trademarks of Gilead Sciences, Inc. or its related companies.
For more information on Kite, please visit the
company’s website at www.kitepharma.com. Follow Kite on social
media on X (@KitePharma) and LinkedIn.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20231211635873/en/
Jacquie Ross, Investors investor_relations@gilead.com
Meaghan Smith, Gilead Media msmith@gilead.com
Anna Padula, Kite Media apadula@kitepharma.com
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