ASH Clinical News ACN_4.5_FULL_ISSUE_DIGITAL - Page 29

KYMRIAH ATTAINED AND SUSTAINED REMISSION IN THE MAJORITY OF PATIENTS
CLINICAL NEWS
Singapore , Taiwan , the U . K ., Lithuania , Portugal , Spain , Slovakia , and Germany . Slovenia and Russia experienced the greatest increases in five-year survival ( ≥20 %), while Brazil , Bulgaria , Croatia , and Poland saw increases of at least 10 percent .
“ International variation in survival for childhood lymphoma was less marked than for childhood ALL ,” the researchers noted . Though they added that “ the marked increase in fiveyear survival among children diagnosed with lymphoma in Brazil ( from 69.2 % in 2000-2004 to 88.2 % in 2010-2014 ) is likely to reflect a real improvement in diagnosis and treatment .”
“ It is crucial for national and regional governments to recognize that populationbased cancer registries are key policy tools , both to monitor the impact of cancer prevention strategies and to evaluate the effectiveness of the health system for all patients diagnosed with cancer ,” the authors concluded .
The study is limited by its reliance on registry data , which may be missing information and may include discrepancies between the countries reporting information . This can affect the comparability of survival estimates . The authors report no financial conflicts .
REFERENCE
Allemani C , Matsuda T , Di Carlo V , et al . Global surveillance of trends in cancer survival 2000 – 14 ( CONCORD-3 ): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries . Lancet . 2018 January 30 . [ Epub ahead of print ]
KYMRIAH ATTAINED AND SUSTAINED REMISSION IN THE MAJORITY OF PATIENTS
GLOBAL PHASE 2 PIVOTAL TRIAL
Primary End Point : ORR at 3 Months 1 *

83 %

( N = 52 / 63 )
achieved remission ( CR / CRi )
10 0 % of patients in remission ( n = 52 ) were MRD – 1
• 96 % of responders ( n = 52 ) achieved remission between Days 26 and 31 , with a median time of 29 days 1
75 % of responders ( n = 52 ) estimated to still be in remission at 6 months 2
• Median duration of CR / CRi § was not yet reached at median follow-up of 4.8 months from response ( range : 1.2 to 14.1 + months ) 1
OVERALL SURVIVAL 2
PROBABILITY (%) OF EVENT FREE
100
80
60
40
20
0
Censoring times All patients ( N = 68 )

89 % estimated survival of infused patients at 6 months ( 77.4 , 94.4 )

Number of events ( n ) All patients : 11

79 % estimated survival of infused patients at 9 and 12 months ( 63.3 , 88.8 )

Kaplan-Meier medians All patients : 16.6 months , 95 % CI ( 16.6 , NE )
TIME ( MONTHS ) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 NUMBER OF PATIENTS STILL AT RISK ALL PATIENTS 68 64 61 57 54 47 36 31 28 22 17 15 13 9 6 3 2 1 0
• Median follow-up of 6.2 months ||
• OS was a secondary efficacy end point of the global phase 2 pivotal trial 3
• Median OS data are not in the label and should be interpreted with caution in a single-arm trial . The statistical significance of OS is not known
• Approximately 84 % ( 57 / 68 ) of patients were still alive ( censored ) at the data cut-off , and only 2 patients were at risk beyond 16 months
CR , complete remission ; CRi , complete remission with incomplete blood count recovery ; MRD –, minimal residual disease negative ; ORR , overall remission rate ; OS , overall survival .
* ORR consisted of CR and CRi ( defined as less than 5 % of blasts in the bone marrow , no evidence of extramedullary disease , and without full recovery of peripheral blood counts with or without blood transfusion ). Remission status was required to be maintained for at least 28 days without clinical evidence of relapse . 1
5 patients who were infused with KYMRIAH were excluded from the efficacy set . The efficacy analysis set ( N = 63 ) is a subset of the full analysis set which consists of all patients treated with KYMRIAH at least 3 months prior to data cut-off . 1 , 2
MRD – was defined as MRD by flow cytometry < 0.01 %. 1
§
Duration of remission ( DOR ) was defined as time since onset of CR or CRi to relapse or death due to underlying cancer , whichever is earlier , censoring for new cancer therapy including stem cell transplant ( n = 52 ). 1
||
OS analysis was conducted on full analysis set ( n = 68 ). 2
WARNINGS AND PRECAUTIONS ( continued ) KYMRIAH REMS to Mitigate CRS and Neurological Toxicities : Because of the risk of CRS and neurological toxicities , KYMRIAH is available only through a restricted program under a Risk Evaluation and Mitigation Strategy ( REMS ) called the KYMRIAH REMS . Further information is available at www . kymriah-rems . com or 1-844-4KYMRIAH ( 1-844-459-6742 ).
References : 1 . Kymriah [ prescribing information ]. East Hanover , NJ : Novartis Pharmaceuticals Corp ; 2017 . 2 . Data on file . Study CTL019B . Novartis Pharmaceuticals Corp ; Feb 2017 . 3 . Data on file . Study CTL019B2202 . Novartis Pharmaceuticals Corp ; Sept 2017 .
Singapore, Taiwan, the U.K., Lithuania, Por- tugal, Spain, Slovakia, and Germany. Slovenia and Russia experienced the greatest increases in five-year survival (≥20%), while Brazil, Bulgaria, Croatia, and Poland saw increases of at least 10 percent. “International variation in survival for childhood lymphoma was less marked than for childhood ALL,” the researchers noted. Though they added that “the marked increase in five- year survival among children diagnosed with registry data, which may be missing informa- tion and may include discrepancies between the countries reporting information. This can affect the comparability of survival estimates. The authors report no financial conflicts. REFERENCE Allemani C, Matsuda T, Di Carlo V, et al. Global surveillance of trends in cancer survival 2000–14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet. 2018 January 30. [Epub ahead of print] S:6.625” KYMRIAH ATTAINED AND SUSTAINED REMISSION IN THE MAJORITY OF PATIENTS GLOBAL PHASE 2 PIVOTAL TRIAL 100% of patients in remission (n=52) were MRD– Primary End Point: ORR at 3 Months 1 * 1‡ • 96% of responders (n=52) achieved remission between Days 26 and 31, with a median time of 29 days 1 83 % (N=52/63) 75% of responders (n=52) estimated to still be in remission at 6 months 2 † • Median duration of CR/CRi § was not yet reached at median follow-up of 4.8 months from response (range: 1.2 to 14.1+ months) 1 achieved remission (CR/CRi) OVERALL SURVIVAL 2 100 • Median follow-up of 6.2 months || • OS was a secondary effi cacy end point of the global phase 2 pivotal trial 3 80 60 40 89 % • Median 2FF&R@FR&VB6V@&RFW'&WFVBvF6WF6vR&ЧG&FR7FF7F66vf66Rb20BvsPW7FFVB7W'ffbgW6VBFVG2@bF2srBBBW7FFVB7W'ffbgW6VBFVG2@B"F2c22ゐ#6V6&rFW0FVG2c DRD2T$U"bDTE25DB$4ccBcDTE0V&W"bWfVG2␤FVG3VW"VF0FVG3bbF2RR4bbR2BRbr"2BRbpSrSBCr3b3##"rR2b2"( "&FVǒBPSrcbFVG0vW&R7FƗfP6V6&VBBFPFF7WBfbBǐ"FVG2vW&RB&6&WBbF05"6WFR&V֗765&6WFR&V֗76vF6WFR&B6VB&V6fW'$N( 2֖&W6GVF6V6RVvFfS%"fW&&V֗76&FS2fW&7W'ffࢢ%"667FVBb5"B5&FVfVB2W72FRRb&7G2FR&R'&rWfFV6RbWG&VGV'F6V6RBvFWBgV&V6fW'bW&W&&B6VG2vF"vFWB&BG&6gW6&V֗767FGW2v2&WV&VBF&RFVBf"BV7B#F0vFWB6Ɩ6WfFV6Rb&V6R( RFVG2vvW&RgW6VBvF$vW&RW6VFVBg&FRVff676WBFRVff67Ǘ626WBc227V'6WBbFRgVǗ626W@v6667G2bFVG2G&VFVBvF$BV7B2F2&"FFF7WBfb ( $N( 2v2FVfVB2$B'fr7FWG'R*pGW&Fb&V֗76D"v2FVfVB2FR66R6WBb5""5&F&V6R"FVFGVRFVFW&ǖr66W"v6WfW"2V&ƖW"6V6&rf"Wr66W"FW&6VFr7FV6VG&7BS"2Ǘ62v26GV7FVBgVǗ626WBc t$u2B$T4UD26FVVB$$T2F֗FvFR5%2BWW&v6F6FW3&V6W6RbFR&6b5%2BWW&v6F6FW2$2f&RǒF&Vv&W7G&7FVB&w&VFW"&6WfVFB֗FvF7G&FVw$T26V@FR$$T2gW'FW"f&F2f&R@wwr淖&&V26"ӃCBD$ӃCBCScsC"&VfW&V6W3&&W67&&rf&FV7BfW"䣠f'F2&6WWF626'#r"FFfR7GVG5D"f'F2&6WWF626'fV"#r2FFfR7GVG5D###"f'F2&6WWF626'6WB#rR^( УR#^( Ф4Ĕ4Uu