ASH Clinical News ACN_4.5_FULL_ISSUE_DIGITAL - Page 28

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 .
Literature Scan (26.8%), and the Czech Republic (16.9%),” the authors reported. 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 Nether- lands, Switzerland, Australia, and New Zealand. Five-year survival was less than 70 percent in Bra- zil, 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 Lymphoid Malignancies The study included 3,011,054 adults from 289 reg- istries 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 Den- mark, 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, The fi rst FDA-approved Bulgaria, Romania, and Russia. CAR-T cell therapy As with myeloid malignan- cies, 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. “... International variation in survival for childhood lymphoma was less marked than for childhood ALL.” —CLAUDIA ALLEMANI, PhD S:6.625” survival increased by 10 percent or more in 14 countries (23%). For lymphoma, the study included 41,196 children from 257 r Vv7G&W2c"6VG&W2ffRזV"vRЧ7FF&FVB7W'ff7B6ǒ&vVBg&FRW&6VB&WGvVV#B#BffRזV"7W'ffv2BV7BW&6VB#6VG&W2CrR6VFpFRR2ffRזV"7W'ffG&VG2vW&RvVW&ǒfBfW FRRV'2&WGvVV#B#CvWfW"7W'ff7&V6VB'RW&6VBFW&6VBFRR2&V$4"ХE$4d$ХE$TDT@E$4d$ХD%$pD4D6B'G&VB2B&V$FVBव$(J"F6vVV6WV6V’24CF&V7FVBvVWF6ǒFfVBWFvW2B6VVFW&F6FVBf"FRG&VFVBbFVG2WF#RV'2bvRvF"6V&V7W'6"7WFRǖ&7F2WVV֖’FB2&Vg&7F'"6V6B"FW"&V6Rऔ%DB4dUEd$Dd"$t$s5DR$TT4R5E$RBUU$t4D4DU0( "7FR&VV6R7G&R5%26VFrfF"ƖfRF&VFVr&V7F267W'&VBFVG2&V6Vfp$FBF֖7FW"$FFVG2vF7FfRfV7F""F'F6&FW'2G&VB6WfW&P"ƖfRF&VFVr5%2vFF6ƗV"( "WW&v6F6FW2v6&R6WfW&R"ƖfRF&VFVr667W"fvrG&VFVBvF$6VFr67W'&VFǒvF5%2F"f"WW&v6WfVG2gFW"G&VFVBvF$&fFP7W'FfR6&R2VVFVB( "$2f&RǒF&Vv&W7G&7FVB&w&VFW"&6WfVFB֗FvF7G&FVw$T26VBFR$$T24E$D4D0Pt$u2B$T4UD07FR&VV6R7G&S5%26VFrfF"ƖfRF&VFVr&V7F267W'&VBfvrG&VFVBvF$7GVG5%267W'&VBsRSBcbFVG2&V6Vfr$6VFrw&FR2"BVw&Fp77FVҒ5%2CR32cbFVG2FRVFFRF6WBb5%2v22F2&vS#"F2bFRSBFVG0vF5%2#rSR&V6VfVBF6ƗV#r2RFVG2&V6VfVB"F6W2bF6ƗV"2bRFVG2&V6VfVB2F6W0bF6ƗV"BB#bRFVG2&V6VfVBFFFb6'F67FW&G2RrWF&VF6RFRVFFRF&W6WFb5%2v2F2&vS3bF2शWfW7FF2b5%26VFRvfWfW"vW"F&&B&W77W&RFff7VG'&VFrB&R766FVBvFWF2&VB6&F2G6gV7FB6wVF&6f7F'2f"6WfW&R5%2&Rv&R֖gW6GV"'W&FVV6G&VB"66VW&FrGV"'W&FVfvrǖFWWFr6VFW&7FfRfV7F2B"fF'&6W76W2FV$gW6gFW"ǖFWWFr6VFW&bFVB2V&W6fVB6W&W2GfW'6R&V7F2g&&V6VFr6VFW&W27FfRV6G&VBfV7F7FfRw&gBg27BF6V6R"v'6VrbWVV֖'W&FVV7W&RF6ƗV"2f&R6FR&"F$gW6F"FVG2f"6v2"7F2b5%2f BV7BBvVV2gFW"G&VFVB6V6VFVG2F6VVVFFRVF6GFVF6VB6v2"7F2`5%267W"BFRf'7B6vb5%2VFFVǒWfVFRFRFVBf"7FƗFB7FGWFRG&VFVBvF7W'FfR6&RF6ƗV"B"6'F67FW&G22F6FVBWW&v6F6FW3WW&v6F6FW2v6&R6WfW&R"ƖfRF&VFVr667W"fvrG&VFV@vF$FR&GbWW&v6F6FW267W'&VBvFvVV2fvr$gW67GVGWW&v6F6FW2vFvVV2gFW"$gW667W'&VBcRRbFVG26VFrw&FR2"@WW&v6F6FW2RbFVG2BsRRbWfVG2&W6fVBvF"F2FR7B6WW&v6F6FW2vW&RVF6R3rRV6WF3BRFVƗ&V#R熖WG2RBG&V"RFW fW7FF2bWW&v6F6FW26VFVBF7GW&&6W2666W6W72F6&VFF6gW6vFF6VW&W2WF6B6F"FVG2f"WW&v6WfVG2BW6VFRFW"6W6W2f"7F2&fFR7W'FfR6&R2VVFVBf"$766FVBWW&v6WfVG2V6R6VR'&Vb7V'b&W67&&rf&F6VFr&VBt$rBFFF'FB6fWGf&Ff"$fvrvW2#`46Ɩ6Ww0#PCP