EAST HANOVER, N.J.,
Dec. 9, 2019 /PRNewswire/
-- Novartis today announced results from two analyses of
real-world experience with Kymriah® (tisagenlecleucel),
the only CAR-T cell therapy approved in two distinct indications.
These analyses are from a readout of a 15-year post-marketing study
that add to and complement the rigor of the Kymriah pivotal trials
with evidence of the Kymriah real-world experience in expanded
groups of patients. When Kymriah was used in the real-world
setting, efficacy and safety were consistent when compared to the
pivotal trials, including the 24-month analysis of JULIET in adults
with r/r diffuse large B cell lymphoma (DLBCL) and ELIANA in
children and young adults with r/r B-cell acute lymphoblastic
leukemia (ALL)1-6. The real-world experience data were
presented at the 61st American Society of Hematology (ASH) annual
meeting.
"With increased experience supplemented by real world data,
physicians like myself have a better understanding of Kymriah and
its safety profile," said lead author of this real-world experience
analysis, Samantha Jaglowski, MD,
The Ohio State University Comprehensive
Cancer Center – Arthur G. James Cancer Hospital and Richard J.
Solove Research Institute (OSUCCC – James). "This along with the
current practice of supportive care for CAR-T therapy provides the
ability to routinely use this therapy in the hospital outpatient
setting, which can reduce financial burden on patients and
hospitals alike1,7."
Real-world experience with Kymriah in adults
with r/r DLBCL
Efficacy
Efficacy outcomes for patients who received
Kymriah in the real-world setting were similar to those
demonstrated in JULIET. In this analysis of 80 patients with r/r
DLBCL for whom three or more months of post-infusion outcomes were
available, the overall response rate (ORR) was 58% including 40%
who achieved a complete response (CR). Median follow-up was 4.5
months1. In the 24-month analysis of the JULIET trial,
ORR was 52% and CR was 38% (N=115) 3.
Safety
The anticipation and management of adverse
events of CAR-T cell therapy have been crucial to successful
administration of this innovative and relatively new type of
therapy. In this analysis of real-world experience with Kymriah
(safety set, N=83), the rate of grade 3 or higher cytokine release
syndrome (CRS) and neurologic events were approximately 4% and 5%,
respectively, as compared to 23% and 11% in the JULIET clinical
trial (safety set, N=115), suggesting safety outcomes appear more
favorable. The real-world analysis used the grading scales ASTCT
for CRS and ICANs for neurologic events, whereas the JULIET trial
used the Penn Grading Scale for CRS and MedDRA SMQ for neurologic
events1,3.
Further, for patients who had CRS, tocilizumab and
corticosteroids were administered in 20% and 4% of patients,
respectively, in the real-world setting, and in 27% and 19% of
patients, respectively, in the JULIET trial8. Some
patients in the real-world setting received tocilizumab earlier
than in the clinical trial experience, indicating earlier use of
supportive care may mitigate rates of high-grade CRS9. A
total of 14 DLBCL patients died after treatment, all due to disease
progression, however no deaths were attributed to toxicities from
Kymriah1.
Patient and product characteristics
More patients in
the real-word analysis had a worse performance status, and on
average, these patients were older and had received more lines of
therapy than those treated in the JULIET trial1-3.
Cell viability is one of many product release specifications for
Kymriah. The commercial specification for the viability
specification of Kymriah in the United
States is set at greater than or equal to 80%. For all other
markets where Kymriah is approved, the cell viability specification
is greater than or equal to 70%. In this US real-world analysis, 29
of the 102 patients with evaluable data received product that was
below 80% cell viability. Efficacy and safety for patients
receiving product with cell viability below the commercial
specification was the same as those receiving commercial
Kymriah1.
These data on the use of Kymriah in r/r DLBCL in the real-world
setting will be presented in an oral session at the ASH annual
meeting (Abstract # 766; Monday, December
9, 3:30 PM EST).
"As pioneers in bringing CAR-T cell therapy to patients, our
dedication to reimagining how CAR-T cell therapy can impact
patients in the future remains steadfast," said Susanne Schaffert, PhD, President, Novartis Oncology. "Our efforts include
gathering and sharing real-world evidence, expanding and improving
our manufacturing capacity and technology and going broader and
deeper in our clinical research with Kymriah and other CAR-T cell
therapies."
Real-world experience with Kymriah in children and
young adults with r/r ALL
Efficacy outcomes were
similar and safety outcomes appear to be more favorable in the real
world setting compared to the ELIANA pivotal trial4-6.
Among 146 children and young adult patients with r/r ALL treated in
the real world setting for whom three or more months of
post-infusion outcomes were available, CR was 85% as compared to
82% in the ELIANA trial (n=79). Median follow-up in the real-world
analysis was 6 months. In this analysis (safety set, N=154), the
rate of grade 3 or higher CRS and neurologic events were 14% and
8%, respectively, as compared to 48% and 13% in the ELIANA clinical
trial. The real-world analysis used the grading scales ASTCT for
CRS and ICANs for neurologic events, whereas the ELIANA trial used
the Penn Grading Scale for CRS and MedDRA SMQ for neurologic
events4-6.
"It is exciting to see how oncologists are using Kymriah and how
patients are responding to it in routine clinical practice," said
Stephan A. Grupp, MD, PhD, Director
of the Cancer Immunotherapy Program and Section Chief of Cell
Therapy and Transplant at Children's Hospital of Philadelphia, and a Professor of Pediatrics in
the Perelman School of Medicine at the University of Pennsylvania. "We are seeing broader
efficacy data that replicate what we saw in the pivotal trial, and
the collection of these data is ensuring that we are getting a
clear view of adverse events when administering Kymriah."
These data on the use of Kymriah in r/r pediatric ALL in the
real-world setting will be presented in a poster presentation at
the ASH annual meeting (Abstract #2619; Sunday, December 8, 6:00 – 8:00 PM EST).
The collection of this real-world experience data was made
possible by a collaboration between the CIBMTR® (Center
for International Blood and Marrow Transplant Research – the
research collaboration between the National Marrow Donor
Program®/Be The Match® and the Medical College of Wisconsin) and Novartis,
developed to capture long-term follow-up of recipients of
Kymriah who agree to participate in the registry. For patients
whose cell viability was below 80%, product is provided through an
established EAP program and long-term follow-up is captured
through the CIBMTR. Globally, 90% patients who have been prescribed
Kymriah have received the final manufactured product, either
commercially, or when out of commercial specification.
Kymriah® (tisagenlecleucel, formerly CTL019)
US Important Safety information
Kymriah may cause side effects that are severe or life-threatening,
such as Cytokine Release Syndrome (CRS) or Neurological Toxicities.
Patients with CRS may experience symptoms including difficulty
breathing, fever (100.4°F/38°C or higher), chills/shaking chills,
severe nausea, vomiting and diarrhea, severe muscle or joint pain,
very low blood pressure, or dizziness/lightheadedness. Patients may
be admitted to the hospital for CRS and treated with other
medications.
Patients with neurological toxicities may experience symptoms
such as altered or decreased consciousness, headaches, delirium,
confusion, agitation, anxiety, seizures, difficulty speaking and
understanding, or loss of balance. Patients should be advised to
call their healthcare provider or get emergency help right away if
they experience any of these signs and symptoms of CRS or
neurological toxicities.
Because of the risk of CRS and neurological toxicities, Kymriah
is only available through a restricted program under a Risk
Evaluation and Mitigation Strategy (REMS) called Kymriah REMS.
Serious allergic reactions, including anaphylaxis, may occur
after Kymriah infusion. Kymriah can increase the risk of
life-threatening infections that may lead to death. Patients should
be advised to tell their healthcare provider right away if they
develop fever, chills, or any signs or symptoms of an
infection.
Patients may experience prolonged low blood cell counts
(cytopenia), where one or more types of blood cells (red blood
cells, white blood cells, or platelets) are decreased. The
patient's healthcare provider will do blood tests to check all of
their blood cell counts after treatment with Kymriah. Patients
should be advised to tell their healthcare provider right away if
they get a fever, are feeling tired, or have bruising or
bleeding.
Patients may experience hypogammaglobulinemia, a condition in
which the level of immunoglobulins (antibodies) in the blood is low
and the risk of infection is increased. It is expected that
patients may develop hypogammaglobulinemia with Kymriah, and may
need to receive immunoglobulin replacement for an indefinite amount
of time following treatment with Kymriah. Patients should tell
their healthcare provider about their treatment with Kymriah before
receiving a live virus vaccine.
After treatment with Kymriah, patients will be monitored
lifelong by their healthcare provider, as they may develop
secondary cancers or recurrence of their cancer.
Patients should not drive, operate heavy machinery, or do other
dangerous activities for eight weeks after receiving Kymriah
because the treatment can cause temporary memory and coordination
problems, including sleepiness, confusion, weakness, dizziness, and
seizures.
Some of the most common side effects of Kymriah are difficulty
breathing, fever (100.4°F/38°C or higher), chills/shaking chills,
confusion, severe nausea, vomiting and diarrhea, severe muscle or
joint pain, very low blood pressure, dizziness/lightheadedness, and
headache. However, these are not all of the possible side effects
of Kymriah. Patients should talk to their healthcare provider for
medical advice about side effects.
Prior to a female patient starting treatment with Kymriah, their
healthcare provider may do a pregnancy test. There is no
information available for Kymriah use in pregnant or breast-feeding
women. Therefore, Kymriah is not recommended for women who are
pregnant or breast feeding. Patients should talk to their
healthcare provider about birth control and pregnancy.
Patients should tell their healthcare provider about all the
medicines they take, including prescription and over-the-counter
medicines, vitamins, and herbal supplements.
After receiving Kymriah, patients should be advised that some
commercial HIV tests may cause a false-positive test result.
Patients should also be advised not to donate blood, organs, or
tissues and cells for transplantation after receiving
Kymriah.
Please see the full Prescribing Information for Kymriah,
including Boxed WARNING, and Medication Guide
at www.Kymriah.com
Disclaimer
This press release contains
forward-looking statements within the meaning of the United States
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statements can generally be identified by words such as
"potential," "can," "will," "plan," "expect," "anticipate," "look
forward," "believe," "committed," "investigational," "pipeline,"
"launch," or similar terms, or by express or implied discussions
regarding potential marketing approvals, new indications or
labeling for the investigational or approved products described in
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such products. You should not place undue reliance on these
statements. Such forward-looking statements are based on our
current beliefs and expectations regarding future events, and are
subject to significant known and unknown risks and uncertainties.
Should one or more of these risks or uncertainties materialize, or
should underlying assumptions prove incorrect, actual results may
vary materially from those set forth in the forward-looking
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approved products described in this press release will be submitted
or approved for sale or for any additional indications or labeling
in any market, or at any particular time. Nor can there be any
guarantee that such products will be commercially successful in the
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About Novartis
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References
- Jaglowski S., et al. Tisagenlecleucel Chimeric Antigen Receptor
(CAR) T-Cell Therapy for Adults with Diffuse Large B-Cell Lymphoma
(DLBCL): Real World Experience from the Center for International
Blood & Marrow Transplant Research (CIBMTR) Cellular Therapy
(CT) Registry [abstract]. In: The 61st ASH Annual Meeting.;
December 7-10; Orlando, Florida.
- Schuster S.., et al. Tisagenlecleucel in Adult
Relapsed/Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med.
December 2018
- Bachanova V., et. al. Correlative Analyses of Cytokine Release
Syndrome and Neurological Events in Tisagenlecleucel-Treated
Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients. ICML
2019 abstract #254
- Grupp S., et al. Tisagenlecleucel Chimeric Antigen Receptor
(CAR) T-Cell Therapy for Relapsed/Refractory Children and Young
Adults with Acute Lymphoblastic Leukemia (ALL): Real World
Experience from the Center for International Blood & Marrow
Transplant Research (CIBMTR) Cellular Therapy (CT) Registry
[abstract]. In: The 61st ASH Annual Meeting.; December 7-10; Orlando,
Florida.
- Maude S., et al. Tisagenlecleucel in children and young adults
with B-cell lymphoblastic leukemia. N Engl J Med.
2018;378(5):439–48
- Grupp S., et al. Updated Analysis of the Efficacy and Safety of
Tisagenlecleucel in Pediatric and Young Adult Patients with
Relapsed/Refractory (r/r) Acute Lymphoblastic Leukemia. 60th
American Society of Hematology Annual Meeting and Exposition.
Abstract #112599.
- Broder M., et al. Economic Burden of Neurologic Toxicities
Associated with Treating Relapsed or Refractory Diffuse Large
B-Cell Lymphoma in the United
States [abstract]. In: The 61th ASH Annual Meeting.;
December 7-10; Orlando, Florida.
- Schuster S.., et al. Consensus Grading of Cytokine Release
Syndrome (CRS) in Adult Patients with Relapsed or Refractory
Diffuse Large B-Cell Lymphoma (r/r DLBCL) Treated with
Tisagenlecleucel on the JULIET Study. Poster #4190
- Novartis Data on file.
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SOURCE Novartis Pharmaceuticals Corporation