NEWS of multi-hit patients had del5q , compared with 34 % of monoallelic patients ( OR = 10 ; 95 % CI 6.1-18 ).
The median overall survival ( OS ) for patients with multi-hit TP53 state was 8.7 months , compared with 2.5 years for monoallelic cases ( hazard ratio [ HR ] = 3.7 ; 95 % CI 2.7-5.0 ; p < 0.001 ). The median OS in wild-type patients was significantly longer , at 3.5 years ( 95 % CI 3.4-3.9 ; p < 0.001 ).
In addition , multi-hit TP53 state was associated with a higher 5-year cumulative incidence of transformation to acute myeloid leukemia ( AML ), compared with monoallelic state ( 44 % vs . 21 %; HR = 5.5 ; 95 % CI 3.1-9.6 ; p < 0.001 ).
“ Of note , all subgroups ( more than one gene mutation , mutation and deletion , mutation and copy neutral loss of heterozygosity ) in multi-hit state had equally dismal outcomes ,” the authors wrote .
According to a multivariable analysis adjusting for age at diagnosis , cytogenetic risk score , and established predictive features , the presence of multi-hit TP53 was an independent predictor of the risk of death ( HR = 2.04 ; 95 % CI 1.6-2.6 ; p < 0.001 ) and AML transformation ( HR = 2.9 ; 95 % CI 1.8-4.7 ; p < 0.001 ). Patients with monoallelic TP53 mutations as well as a VAF > 22 % had a significantly greater risk of mortality compared
ADULT PATIENTS WITH R / R MANTLE CELL LYMPHOMA ( MCL ) 1 , 2
AN INCREDIBLE RESPONSE WITH
TECARTUS 1
87 % ORR ( n = 52 / 60 ) 1
DEEP
62 % CR ( n = 37 / 60 ) 1
DURABLE
The median duration of response was not reached at a median study follow-up of 12.3 months 1 , 4
RAPID
1 month median time to response ( range : 0.8 – 3.1 months ) 1
a BTKi ( ibrutinib or acalabrutinib ). In total , 68 patients were treated with TECARTUS , and 60 patients were evaluable for effi cacy . Primary effi cacy endpoint was ORR ; selected secondary endpoints included DOR and safety . 1 , 5
Hypersensitivity Reactions : Serious hypersensitivity reactions , including anaphylaxis , may occur due to dimethyl sulfoxide ( DMSO ) or residual gentamicin in TECARTUS .
Severe Infections : Severe or life-threatening infections occurred in patients after TECARTUS infusion . In ZUMA-2 , infections ( all grades ) occurred in 56 % of patients . Grade 3 or higher infections , including bacterial , viral , and fungal infections , occurred in 30 % of patients . TECARTUS should not be administered to patients with clinically signifi cant active systemic infections . Monitor patients for signs and symptoms of infection before and after infusion and treat appropriately . Administer prophylactic antimicrobials according to local guidelines .
Febrile neutropenia was observed in 6 % of patients after TECARTUS infusion and may be concurrent with CRS . In the event of febrile neutropenia , evaluate for infection and manage with broad-spectrum antibiotics , fl uids , and other supportive care as medically indicated .
Viral Reactivation Hepatitis B virus ( HBV ) reactivation , in some cases resulting in fulminant hepatitis , hepatic failure , and death , can occur in patients treated with drugs directed against B cells . Perform screening for HBV , HCV , and HIV in accordance with clinical guidelines before collection of cells for manufacturing .
Prolonged Cytopenias : Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and TECARTUS infusion . In ZUMA-2 , Grade ≥3 cytopenias not resolved by Day 30 following TECARTUS infusion occurred in 55 % of patients and included thrombocytopenia ( 38 %), neutropenia ( 37 %), and anemia ( 17 %). Monitor blood counts after infusion .
Hypogammaglobulinemia and B-cell aplasia can occur in patients receiving treatment with TECARTUS . In ZUMA-2 , hypogammaglobulinemia occurred in 16 % of patients . Monitor immunoglobulin levels after treatment with TECARTUS and manage using infection precautions , antibiotic prophylaxis , and immunoglobulin replacement . The safety of immunization with live viral vaccines during or following TECARTUS treatment has not been studied . Vaccination with live virus vaccines is not recommended for at least six weeks prior to the start of lymphodepleting chemotherapy , during treatment , and until immune recovery following treatment with TECARTUS .
Secondary Malignancies may develop . Monitor life-long for secondary malignancies . In the event that it occurs , contact Kite at 1-844-454-KITE ( 5483 ) to obtain instructions on patient samples to collect for testing .
Effects on Ability to Drive and Use Machines : Due to the potential for neurologic events , including altered mental status or seizures , patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following TECARTUS infusion . Advise patients to refrain from driving and engaging in hazardous activities , such as operating heavy or potentially dangerous machinery , during this period .
Adverse Reactions : The most common adverse reactions ( incidence ≥ 20 %) were pyrexia , CRS , hypotension , encephalopathy , fatigue , tachycardia , arrhythmia , infection – pathogen unspecifi ed , chills , hypoxia , cough , tremor , musculoskeletal pain , headache , nausea , edema , motor dysfunction , constipation , diarrhea , decreased appetite , dyspnea , rash , insomnia , pleural effusion , and aphasia . Serious adverse reactions occurred in 66 % of patients . The most common serious adverse reactions (> 2 %) were encephalopathy , pyrexia , infection – pathogen unspecifi ed , CRS , hypoxia , aphasia , renal insuffi ciency , pleural effusion , respiratory failure , bacterial infections , dyspnea , fatigue , arrhythmia , tachycardia , and viral infections .
Please see Brief Summary of full Prescribing Information , including BOXED WARNING and Medication Guide , for TECARTUS on following pages .
BTKi = Bruton ’ s tyrosine kinase inhibitor ; CAR = chimeric antigen receptor ; CR = complete response ; DOR = duration of response ; ORR = objective response rate ; R / R = relapsed or refractory .
References : 1 . TECARTUS™ ( brexucabtagene autoleucel ). Prescribing information . Kite Pharma , Inc ; 2020 . 2 . Kite , a Gilead Company [ press release ]. U . S . FDA approves Kite ’ s TECARTUS™ , the first and only CAR T treatment for relapsed or refractory mantle cell lymphoma . Published July 24 , 2020 . https :// www . kitepharma . com / news / press-releases / 2020 / 7 / us-fda-approves-kites-tecartus-the-first-and-onlycar-t-treatment-for-relapsed-or-refractory-mantle-cell-lymphoma . Accessed July 24 , 2020.3 . Data on file [ 1 ]. Kite Pharma , Inc ; 2020 . 4 . Data on file [ 2 ]. Kite Pharma , Inc ; 2020 . 5 . Wang M , Munoz J , Goy A , et al . KTE-X19 CAR T-cell therapy in relapsed or refractory mantle cell lymphoma . N Engl J Med . 2020 ; 382 ( 14 ): 1331-1342 .
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