Press Release: Novartis Kymriah(R) demonstrates consistent efficacy and safety outcomes in US patients when used in real-world setting

-- Efficacy in DLBCL confirmed results seen in the pivotal trial despite

treatment of a broader population, including older and more heavily

pretreated patients1-3

-- Fewer known CAR-T cell therapy adverse events for patients with DLBCL,

specifically rates of high-grade cytokine release syndrome (4%) and

neurologic events (5%), were observed compared with the pivotal clinical

trials1-3

-- In children and young adults with ALL, efficacy outcomes were similar and

safety outcomes appear to be more favorable compared to the pivotal

trial4

-- Understanding the Kymriah safety profile, and increased experience with

administration in real-world practice supports use in the outpatient

setting

Basel, December 9, 2019 -- Novartis today announced results from two

analyses of real-world experience with Kymriah(R) (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 alike(1,7)."

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 months(1). 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

events(1,3).

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

trial(8). 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 CRS(9). A total of 14

DLBCL patients died after treatment, all due to disease progression,

however no deaths were attributed to toxicities from Kymriah(1).

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 trial(1-3).

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 Kymriah(1).

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

trial(4-6). 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 events(4-6).

"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(R) (Center for International Blood and

Marrow Transplant Research -- the research collaboration between the

National Marrow Donor Program(R) /Be The Match(R) 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(R) (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

(100.4degF/38degC 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.

(MORE TO FOLLOW) Dow Jones Newswires

December 09, 2019 14:45 ET (19:45 GMT)