– Analysis Shows Manufacturing of Yescarta
in Second-Line Treatment of Relapsed/Refractory Large B-cell
Lymphoma Can Help Reduce Time from Leukapheresis to Infusion vs.
Third-Line+ Treatment –
– Data Builds on Previous Evidence on the
Association Between Timely Infusion and Patient Outcomes –
– Preliminary Results Supporting Safety and
Feasibility of Outpatient Administration of Yescarta and Tecartus®
to be Presented –
Kite, a Gilead Company (Nasdaq: GILD), today announced results
from three new analyses for Yescarta® (axicabtagene ciloleucel) in
relapsed/refractory (R/R) large B-cell lymphoma (LBCL), including
both new clinical research and real-world evidence highlighting
manufacturing and product characteristics of Yescarta, and
outpatient administration of both Yescarta and Tecartus®
(brexucabtagene autoleucel) at the 2024 European Hematology
Association (EHA) Annual Congress, June 13-16, Madrid.
Results include a comparative analysis of real-world and
clinical trial data (abstract P1425), which show higher
manufacturing success rate and improved T-cell performance for
Yescarta in second-line versus third-line plus treatment of R/R
LBCL. Rapid and efficient manufacturing of CAR T-cell therapy can
help reduce the time from leukapheresis to cell therapy
infusion.
“We are committed to improving survival outcomes for people
living with difficult-to-treat blood cancers,” said Ibrahim
Elhoussieny, Vice President, Medical Affairs, Kite. “These new data
support the potential benefit of utilizing Yescarta in earlier
lines of treatment, both in terms of manufacturing success and
product characteristics. Additional data support the safety and
feasibility of administering CAR T-cell therapy in the outpatient
setting. These data contribute to the body of evidence for
efficient utilization and delivery of Yescarta and Tecartus and
further support our ambition for patients.”
Abstract P1425
Real-World Manufacturing Experience of Axicabtagene Ciloleucel
for Patients with Relapsed or Refractory Large B-Cell Lymphoma
Treated in Second Line versus Third Line of Therapy and Beyond
An analysis of 4,175 patients compared the real-world
manufacturing experience and clinical trial product characteristics
for patients with R/R LBCL in second-line versus third-line plus
treatment. The analysis found a statistically significant higher
number of patients with R/R LBCL who received Yescarta as a
second-line treatment (95.08% of 1,341 patients) achieved
first-pass manufacturing success rate (FP-MSR); compared with
patients treated third-line and beyond (92.48% of the 2,834). This
2.60% difference suggests that 26 more lots of Yescarta are
successfully manufactured per 1,000 in the first attempt for
patients in second-line versus patients in third-line or beyond.
The FP-MSR is defined as the ability to manufacture and disposition
patient lots within specification at first attempt, critical to
maintaining a timely and dependable manufacturing process. Given
that higher FP-MSR lessens the need for multiple manufacturing
attempts, patients receiving Yescarta in second-line could
potentially experience shorter vein-to-vein times.
Results further assessed the percentage of naïve-like T-cells in
apheresis among evaluable patients from ZUMA-1 (third-line) and
ZUMA-7 (second-line). The analysis found the median percentage of
naïve-like T-cells in patient leukapheresis was 9.28% (range,
0.20-45.07; n=126; P<.0001) for second-line, versus 4.11%
(range, 0.09-56.60; n=100) for third-line plus; demonstrating
patients treated in second-line setting displayed a median of
approximately two times as many naïve-like T-cells versus
third-line plus patients. These results indicate capturing a
greater naïve-like T-cell population in the initial leukapheresis
material with earlier CAR T-cell therapy intervention, which is
numerically associated with improved response.
“These data suggest a notable number of patients living with
relapsed/refractory large B-cell lymphoma could benefit from
receiving axi-cel as second-line versus third-line treatment and
beyond,” said Dr. Jason Westin, study lead and Director of Lymphoma
Clinical Research Program and Section Chief of Aggressive Lymphoma
research team at The University of Texas MD Anderson Cancer Center.
“Patients treated in second-line have both a higher rate of success
of having their cell therapy manufactured at the first attempt, as
well as twice as many, naïve-like T-cells collected during
leukapheresis, both of which support patients potentially having a
shorter vein-to-vein time. When combining these two factors, we
hope this will lead to improved patient outcomes.”
Additional Data Presented for
Outpatient Administration
Kite will also present two studies which evaluate the safety and
efficacy of cell therapy administration within the outpatient
setting. Preliminary findings, including safety data, from the
ZUMA-24 study suggest that outpatient administration of Yescarta is
feasible, when administered at a qualified treatment center, at the
physician’s discretion with appropriate monitoring. The REMS
program for healthcare facilities that dispense and administer
Yescarta is described in greater detail below.
Abstract P1159
ZUMA-24 Preliminary Analysis: A Phase 2 Study of Axicabtagene
Ciloleucel in the Outpatient Setting with Prophylactic
Corticosteroids in Patients with Relapsed/Refractory Large B-Cell
Lymphoma
ZUMA-24 is an ongoing, single-arm, open-label, multicenter,
Phase 2 study evaluating the safety and efficacy of Yescarta with
prophylactic corticosteroid use in patients with R/R LBCL, after
one or more prior lines of therapy, in the outpatient setting. The
preliminary analysis of 30 patients who underwent outpatient dosing
of Yescarta, after a median follow-up of five months, demonstrated
that the safety and efficacy of Yescarta was consistent with
previous clinical and real-world studies.
Abstract P1191
Updated Trends in Real-World Outpatient (OP) Administration of
Axicabtagene Ciloleucel (Axi-Cel) and Brexucabtagene Autoleucel
(Brexu-Cel) in Relapsed/Refractory (R/R) Non-Hodgkin Lymphoma
(NHL)
A real-world outpatient study assessed trends in safety and
hospitalization for patients with R/R Non-Hodgkin lymphoma (NHL)
who received Yescarta and Tecartus at Mayo Clinic. Safety endpoints
included CRS, immune effector cell-associated neurotoxicity
syndrome (ICANS) and hospitalization rates. Analysis of safety
trends reported that outpatient administration of Yescarta and
Tecartus was possible without added toxicity.
About Yescarta
Please see full 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 response rate.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory
trial(s).
U.S. IMPORTANT SAFETY INFORMATION
BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC
TOXICITIES and SECONDARY HEMATOLOGICAL MALIGNANCIES
- 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.
- T cell malignancies have occurred following treatment of
hematologic malignancies with BCMA- and CD19-directed genetically
modified autologous T cell immunotherapies, including
YESCARTA.
- 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
following treatment with YESCARTA. CRS occurred in 90% (379/422) of
patients with non-Hodgkin lymphoma (NHL) receiving YESCARTA,
including ≥ Grade 3 (Lee grading system1) CRS in 9%. CRS occurred
in 93% (256/276) of patients with large B-cell lymphoma (LBCL),
including ≥ Grade 3 CRS in 9%. Among patients with LBCL who died
after receiving YESCARTA, four 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 to 12 days)
and the median duration of CRS was 7 days (range: 2 to 58 days).
For patients with LBCL in ZUMA-7, the median time to onset of CRS
was 3 days following infusion (range: 1 to 10 days) and the median
duration was 7 days (range: 2 to 43 days).
CRS occurred in 84% (123/146) of patients with indolent
non-Hodgkin lymphoma (iNHL) in ZUMA-5, including ≥ Grade 3 CRS in
8%. Among patients with iNHL who died after receiving YESCARTA, one
patient had an ongoing CRS event at the time of death. The median
time to onset of CRS was 4 days (range: 1 to 20 days) and the
median duration was 6 days (range: 1 to 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
(HLH/MAS).
The impact of tocilizumab and/or corticosteroids on the
incidence and severity of CRS was assessed in two 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 to 8 days) and the median duration of
CRS was 7 days (range: 2 to 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 at
which point the patients were managed with tocilizumab and/or
therapeutic doses of corticosteroids with no patients developing
Grade 3 or higher CRS. The median time to onset of CRS was 5 days
(range: 1 to 15 days) and the median duration of CRS was 4 days
(range: 1 to 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
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 (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 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 higher grade of neurologic toxicities or prolongation of
neurologic toxicities, delay the onset 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 about 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 or higher
infections occurred in 17% of patients, including ≥ Grade 3 or
higher 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
Patients treated with YESCARTA may develop secondary
malignancies. T cell malignancies have occurred following treatment
of hematologic malignancies with BCMA- and CD19-directed
genetically modified autologous T cell immunotherapies, including
YESCARTA. Mature T cell malignancies, including CAR-positive
tumors, may present as soon as weeks following infusion, and may
include fatal outcomes.
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 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 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 pathogen
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
pathogen unspecified, tachycardia, febrile neutropenia,
musculoskeletal pain, nausea, tremor, chills, diarrhea,
constipation, decreased appetite, cough, vomiting, hypoxia,
arrhythmia, and dizziness.
About Tecartus
Please see full FDA Prescribing Information, including BOXED
WARNING and Medication Guide.
Tecartus is a CD19-directed genetically modified autologous T
cell immunotherapy indicated for the treatment of:
- Adult patients with relapsed or refractory mantle cell lymphoma
(MCL). This indication is approved under accelerated approval based
on overall response rate and durability of response. Continued
approval for this indication may be contingent upon verification
and description of clinical benefit in a confirmatory trial.
- Adult patients with relapsed or refractory B-cell precursor
acute lymphoblastic leukemia (ALL).
U.S. IMPORTANT SAFETY INFORMATION
BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC
TOXICITIES and SECONDARY HEMATOLOGICAL MALIGNANCIES
- Cytokine Release Syndrome (CRS), including life-threatening
reactions, occurred in patients receiving Tecartus. Do not
administer Tecartus to patients with active infection or
inflammatory disorders. Treat severe or life-threatening CRS with
tocilizumab or tocilizumab and corticosteroids.
- Neurologic toxicities, including life-threatening reactions,
occurred in patients receiving Tecartus, including concurrently
with CRS or after CRS resolution. Monitor for neurologic toxicities
after treatment with Tecartus. Provide supportive care and/or
corticosteroids as needed.
- T cell malignancies have occurred following treatment of
hematologic malignancies with BCMA- and CD19-directed genetically
modified autologous T cell immunotherapies
- Tecartus 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), including
life-threatening reactions, occurred following treatment with
Tecartus. CRS occurred in 92% (72/78) of patients with ALL,
including ≥ Grade 3 (Lee grading system) CRS in 26% of patients.
Three patients with ALL had ongoing CRS events at the time of
death. The median time to onset of CRS was five days (range: 1 to
12 days) and the median duration of CRS was eight days (range: 2 to
63 days) for patients with ALL.
Ensure that a minimum of two doses of tocilizumab are available
for each patient prior to infusion of Tecartus. Following infusion,
monitor patients for signs and symptoms of CRS daily for at least
seven days at the certified healthcare facility, and for four 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 Events, including those that were fatal or
life-threatening, occurred following treatment with Tecartus.
Neurologic events occurred in 87% (68/78) of patients with ALL,
including ≥ Grade 3 in 35% of patients. The median time to onset
for neurologic events was seven days (range: 1 to 51 days) with a
median duration of 15 days (range: 1 to 397 days) in patients with
ALL. For patients with MCL, 54 (66%) patients experienced CRS
before the onset of neurological events. Five (6%) patients did not
experience CRS with neurologic events and eight patients (10%)
developed neurological events after the resolution of CRS.
Neurologic events resolved for 119 out of 134 (89%) patients
treated with Tecartus. Nine patients (three patients with MCL and
six patients with ALL) had ongoing neurologic events at the time of
death. For patients with ALL, neurologic events occurred before,
during, and after CRS in 4 (5%), 57 (73%), and 8 (10%) of patients;
respectively. Three patients (4%) had neurologic events without
CRS. The onset of neurologic events can be concurrent with CRS,
following resolution of CRS or in the absence of CRS.
The most common neurologic events (>10%) were similar in MCL
and ALL and included encephalopathy (57%), headache (37%), tremor
(34%), confusional state (26%), aphasia (23%), delirium (17%),
dizziness (15%), anxiety (14%), and agitation (12%). Serious events
including encephalopathy, aphasia, confusional state, and seizures
occurred after treatment with Tecartus.
Monitor patients daily for at least seven days for patients with
MCL and at least 14 days for patients with ALL at the certified
healthcare facility and for four weeks following infusion for signs
and symptoms of neurologic toxicities and treat promptly.
REMS Program: Because of the risk of CRS and neurologic
toxicities, Tecartus is available only through a restricted program
under a Risk Evaluation and Mitigation Strategy (REMS) called the
Yescarta and Tecartus REMS Program which requires that:
- Healthcare facilities that dispense and administer Tecartus
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 two doses of tocilizumab
are available for each patient for infusion within two hours after
Tecartus infusion, if needed for treatment of CRS.
- Certified healthcare facilities must ensure that healthcare
providers who prescribe, dispense, or administer Tecartus 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: Serious hypersensitivity
reactions, including anaphylaxis, may occur due to dimethyl
sulfoxide (DMSO) or residual gentamicin in Tecartus.
Severe Infections: Severe or life-threatening infections
occurred in patients after Tecartus infusion. Infections (all
grades) occurred in 56% (46/82) of patients with MCL and 44%
(34/78) of patients with ALL. Grade 3 or higher infections,
including bacterial, viral, and fungal infections, occurred in 30%
of patients with ALL and MCL. Tecartus should not be administered
to patients with clinically significant active systemic infections.
Monitor patients for signs and symptoms of infection before and
after Tecartus infusion and treat appropriately. Administer
prophylactic antimicrobials according to local guidelines.
Febrile neutropenia was observed in 6% of patients with MCL and
35% of patients with ALL after Tecartus infusion and may be
concurrent with CRS. The febrile neutropenia in 27 (35%) of
patients with ALL includes events of “febrile neutropenia” (11
(14%)) plus the concurrent events of “fever” and “neutropenia” (16
(21%)). 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, life-threatening and fatal
opportunistic infections have been reported. The possibility of
rare infectious etiologies (e.g., fungal and viral infections such
as HHV-6 and progressive multifocal leukoencephalopathy) should be
considered in 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. 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 Tecartus
infusion. In patients with MCL, Grade 3 or higher cytopenias not
resolved by Day 30 following Tecartus infusion occurred in 55%
(45/82) of patients and included thrombocytopenia (38%),
neutropenia (37%), and anemia (17%). In patients with ALL who were
responders to Tecartus treatment, Grade 3 or higher cytopenias not
resolved by Day 30 following Tecartus infusion occurred in 20%
(7/35) of the patients and included neutropenia (12%) and
thrombocytopenia (12%); Grade 3 or higher cytopenias not resolved
by Day 60 following Tecartus infusion occurred in 11% (4/35) of the
patients and included neutropenia (9%) and thrombocytopenia (6%).
Monitor blood counts after Tecartus infusion.
Hypogammaglobulinemia: B cell aplasia and
hypogammaglobulinemia can occur in patients receiving treatment
with Tecartus. Hypogammaglobulinemia was reported in 16% (13/82) of
patients with MCL and 9% (7/78) of patients with ALL. Monitor
immunoglobulin levels after treatment with Tecartus and manage
using infection precautions, antibiotic prophylaxis, and
immunoglobulin replacement.
The safety of immunization with live viral vaccines during or
following Tecartus treatment has not been studied. Vaccination with
live virus vaccines is not recommended for at least six weeks prior
to the start of lymphodepleting chemotherapy, during Tecartus
treatment, and until immune recovery following treatment with
Tecartus.
Secondary Malignancies may develop. T cell malignancies
have occurred following treatment of hematologic malignancies with
BCMA- and CD19-directed genetically modified autologous T cell
immunotherapies. Mature T cell malignancies, including CAR-positive
tumors, may present as soon as weeks following infusion, and may
include fatal outcomes. 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 Tecartus
infusion. Advise patients to refrain from driving and engaging in
hazardous activities, such as operating heavy or potentially
dangerous machinery, during this period.
Adverse Reactions: The most common non-laboratory adverse
reactions (≥ 20%) were fever, cytokine release syndrome,
hypotension, encephalopathy, tachycardia, nausea, chills, headache,
fatigue, febrile neutropenia, diarrhea, musculoskeletal pain,
hypoxia, rash, edema, tremor, infection with pathogen unspecified,
constipation, decreased appetite, and vomiting. The most common
serious adverse reactions (≥ 2%) were cytokine release syndrome,
febrile neutropenia, hypotension, encephalopathy, fever, infection
with pathogen unspecified, hypoxia, tachycardia, bacterial
infections, respiratory failure, seizure, diarrhea, dyspnea, fungal
infections, viral infections, coagulopathy, delirium, fatigue,
hemophagocytic lymphohistiocytosis, musculoskeletal pain, edema,
and paraparesis.
Please see full Prescribing Information, including BOXED
WARNING and Medication Guide.
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.
Gilead acquired Kite in 2017.
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 Tecartus and
Yescarta; uncertainties relating to regulatory applications and
related filing and approval timelines, including pending or
potential applications for indications currently under evaluation;
and any assumptions underlying any of the foregoing. These and
other risks, uncertainties and other factors are described in
detail in Gilead’s Quarterly Report on Form 10-Q for the quarter
ended March 31, 2024, 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, Tecartus, Gilead
and the Gilead logo 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/20240614729632/en/
Jacquie Ross, Investors investor_relations@gilead.com
Meaghan Smith, Gilead Media Public_Affairs@gilead.com
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