Literature Scan
( 26.8 %), and the Czech Republic ( 16.9 %),” the authors reported .
Lymphoid Malignancies The study included 3,011,054 adults from 289 registries in 62 countries . Five-year , age-standardized survival rates ranged from 40 to 70 percent in most countries , but again , were lower in Asia and Central and South America .
Five-year survival was 70 percent or higher in Denmark , Iceland , Latvia , Belgium , France , Switzerland , and Australia , while survival in the U . S . ranged from 60 to 69 percent . Survival was under 50 percent in Argentina , Brazil , Chile , Ecuador , Martinique , China , India , Thailand , Bulgaria , Romania , and Russia .
As with myeloid malignancies , five-year survival rates for lymphoid malignancies generally increased over the 15 years of the CONCORD program : Survival rose by 5 percent to 10 percent in 23 countries ( 37 %) and by more than 10 percent in 14 countries ( 23 %).
Pediatric Cancers : Acute Lymphocytic Leukemia ( ALL ) and Lymphoma For ALL , the study included 87,351 children from 254 registries in 61 countries . Global survival rates ranged widely , from 50 percent to more than 90 percent .
Among children diagnosed between 2010 and 2014 , five-year age-standardized survival was highest ( ≥90 %) in Puerto Rico , Canada , the U . S ., Denmark , Finland , the U . K ., Portugal , Belgium , Germany , the Netherlands , Switzerland , Australia , and New Zealand .
Five-year survival was less than 70 percent in Brazil , Chile , Columbia , and Peru , “ even after adjustment for the very high background mortality in childhood ” in these areas , the researchers noted . Survival was less than 60 percent in China , Ecuador , and Mexico .
Between 1995 to 1999 and 2010 to 2014 , five-year
The first FDA-approved
CAR-T cell therapy
Child portrayed is not a real KYMRIAH patient .
KYMRIAH
CAR-
TRANSFORM TREATMENT survival increased by 10 percent or more in 14 countries ( 23 %).
For lymphoma , the study included 41,196 children from 257 registries in 62 countries . Five-year agestandardized survival most commonly ranged from 80 to 95 percent . Between 2010 and 2014 , five-year survival was at least 90 percent in 29 countries ( 47 %), including the U . S .
Five-year survival trends were generally flat over the 15 years between 2000 and 2014 ; however , survival increased by 5 percent to 10 percent in the U . S ., Korea ,
TRANSFORM TOMORROW
INDICATION
KYMRIAH™ ( tisagenlecleucel ) is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia ( ALL ) that is refractory or in second or later relapse .
“ ... International variation in survival for childhood lymphoma was less marked than for childhood ALL .”
— CLAUDIA ALLEMANI , PhD
26 ASH Clinical News
IMPORTANT SAFETY INFORMATION FOR KYMRIAH
WARNING : CYTOKINE RELEASE SYNDROME AND NEUROLOGICAL TOXICITIES
• Cytokine Release Syndrome ( CRS ), including fatal or life-threatening reactions , occurred in patients receiving KYMRIAH . Do not administer KYMRIAH to patients with active infection or inflammatory disorders . Treat severe or life-threatening CRS with tocilizumab .
• Neurological toxicities , which may be severe or life-threatening , can occur following treatment with KYMRIAH , including concurrently with CRS . Monitor for neurological events after treatment with KYMRIAH . Provide supportive care as needed .
• KYMRIAH is available only through a restricted program under a Risk Evaluation and Mitigation Strategy ( REMS ) called the KYMRIAH REMS .
CONTRAINDICATIONS None
WARNINGS AND PRECAUTIONS Cytokine Release Syndrome : CRS , including fatal or life-threatening reactions , occurred following treatment with KYMRIAH . In Study 1 , CRS occurred in 79 % ( 54 / 68 ) of patients receiving KYMRIAH , including grade 3 or 4 ( Penn grading system ) CRS in 49 % ( 33 / 68 ) of patients . The median time to onset of CRS was 3 days ( range : 1-22 days ). Of the 54 patients with CRS , 27 ( 50 %) received tocilizumab ; 7 ( 13 %) patients received 2 doses of tocilizumab , 3 ( 6 %) patients received 3 doses of tocilizumab and 14 ( 26 %) patients received addition of corticosteroids ( e . g . methylprednisolone ). The median time to resolution of CRS was 8 days ( range : 1-36 days ).
Key manifestations of CRS may include high fever , lower than normal blood pressure , difficulty breathing , and may be associated with hepatic , renal , and cardiac dysfunction , and coagulopathy . Risk factors for severe CRS are high pre-infusion tumor burden , uncontrolled or accelerating tumor burden following lymphodepleting chemotherapy , active infections , and / or inflammatory processes . Delay KYMRIAH infusion after lymphodepleting chemotherapy if patient has unresolved serious adverse reactions from preceding chemotherapies , active uncontrolled infection , active graft vs host disease , or worsening of leukemia burden .
Ensure tocilizumab is available on-site prior to KYMRIAH infusion . Monitor patients for signs or symptoms of CRS for at least 4 weeks after treatment . Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur . At the first sign of CRS , immediately evaluate the patient for hospitalization and institute treatment with supportive care , tocilizumab and / or corticosteroids as indicated .
Neurological Toxicities : Neurological toxicities , which may be severe or life-threatening , can occur following treatment with KYMRIAH . The majority of neurological toxicities occurred within 8 weeks following KYMRIAH infusion . In Study 1 , neurological toxicities within 8 weeks after KYMRIAH infusion occurred in 65 % of patients , including grade 3 or 4 neurological toxicities in 18 % of patients , and 75 % of events resolved within 12 days . The most common neurological toxicities were headache ( 37 %), encephalopathy ( 34 %), delirium ( 21 %), anxiety ( 13 %), and tremor ( 9 %). Other manifestations of neurological toxicities included disturbances in consciousness , disorientation , confusion , agitation , seizures , mutism and aphasia . Monitor patients for neurological events and exclude other causes for symptoms . Provide supportive care as needed for KYMRIAH-associated neurological events .
Please see Brief Summary of Prescribing Information , including Boxed WARNING , and additional Important Safety Information for KYMRIAH on following pages .