ASH Clinical News ACN_4.5_FULL_ISSUE_DIGITAL - Page 33

CLINICAL NEWS lowest among Asians ($ 630 ; ranges not reported ; p = 0.009 ) but increased most steadily among Hispanics ( p < 0.001 ).
Drug claims any time after an MM diagnosis were highest among Hispanics ($ 5,400 ), followed by Asians ($ 4,700 ), African-Americans ($ 3,900 ), and whites ($ 3,300 ; p < 0.001 ). African-American patients also had the highest number of total claims ( p < 0.001 ). “ These differences are not clearly explained by
Metabolism and nutrition disorders : tumor lysis syndrome ( 6 %) Vascular disorders : capillary leak syndrome ( 3 %) Laboratory Abnormalities
Selected laboratory abnormalities worsening from baseline Grade 0-2 to Grade 3-4 are shown in Table 3 .
Table 3 . Selected Other Laboratory Abnormalities Worsening from Baseline Grade 0-2 to Grade 3-4 Following Treatment with KYMRIAH based on CTCAE a ( N = 68 )
Grade 3 or 4 (%)
Increased Aspartate Aminotransferase 28 Hypokalemia 27 Increased Alanine Aminotransferase 21 Increased bilirubin 21 Hypophosphatemia 19 a
CTCAE = Common Terminology Criteria for Adverse Events version 4.03
All patients experienced neutropenia , anemia and thrombocytopenia . See Table 4 for the incidences of Grade 3 and Grade 4 prolonged thrombocyto - penia and prolonged neutropenia in responding patients .
Table 4 . Prolonged Cytopenias Following Treatment with KYMRIAH
N = 52 (%)
Day 28 Day 56 Prolonged neutropenia a 40 17 Prolonged thrombocytopenia a 27 12 a Grade 3 and 4 observed within 14 days after Day 28 or Day 56 in responding
patients
6.2 Immunogenicity In clinical studies , humoral immunogenicity of KYMRIAH was measured by determination of anti-murine CAR19 antibodies ( anti-m CAR19 ) in serum pre- and post-administration . The majority of patients ( 86 %) tested positive for pre-dose anti-m CAR19 antibodies in Study 1 ; however , the preexisting and treatment-induced antibodies were not associated with an impact on clinical response and did not have an impact on the initial expansion and persistence of KYMRIAH . Persistence of KYMRIAH was similar between patients with positive post-infusion anti-m CAR19 antibodies compared with patients with negative post-infusion anti-m CAR19 antibodies . There is no evidence that the presence of preexisting and treatment-induced anti-mCAR19 antibodies impact the safety or effectiveness of KYMRIAH .
7 DRUG INTERACTIONS HIV and the lentivirus used to make KYMRIAH have limited , short spans of identical genetic material ( RNA ). Therefore , some commercial HIV nucleic acid test ( NAT ) tests may yield false-positive results in patients who have received KYMRIAH .
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary
There are no available data with KYMRIAH use in pregnant women . No animal reproductive and developmental toxicity studies have been conducted with KYMRIAH to assess whether it can cause fetal harm when administered to a pregnant woman . It is not known if KYMRIAH has the potential to be transferred to the fetus . Based on the mechanism of action , if the transduced cells cross the placenta , they may cause fetal toxicity , including B-cell lympho - cytopenia . Therefore , KYMRIAH is not recommended for women who are pregnant , and pregnancy after KYMRIAH administration should be discussed with the treating physician . Report pregnancies to Novartis Pharmaceuticals Corporation at 1-888-669-6682 .
In the U . S . general population , the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 %-4% and 15 %-20%, respectively .
8.2 Lactation Risk Summary
There is no information regarding the presence of KYMRIAH in human milk , the effect on the breastfed infant , and the effects on milk production . The developmental and health benefits of breastfeeding should be considered along with the mother ’ s clinical need for KYMRIAH and any potential adverse effects on the breastfed infant from KYMRIAH or from the underlying maternal condition . disease presentation or complications , because the patterns are not similar to our analysis of MDEs in these patients ,” the researchers noted .
In the entire population , overall survival ( OS ) was 21 percent at five years , 6 percent at 10 years , and 2 percent at 15 years .
People with higher median incomes (>$ 61,600 vs . ≤ $ 34,700 ) experienced better OS ( hazard ratio [ HR ] = 0.92 ; 95 % CI
8.3 Females and Males of Reproductive Potential Pregnancy Testing
Pregnancy status of females with reproductive potential should be verified . Sexually-active females of reproductive potential should have a pregnancy test prior to starting treatment with KYMRIAH .
Contraception
See the prescribing information for fludarabine and cyclophosphamide for information on the need for effective contraception in patients who receive the lymphodepleting chemotherapy .
There are insufficient exposure data to provide a recommendation concerning duration of contraception following treatment with KYMRIAH .
Infertility There are no data on the effect of KYMRIAH on fertility .
8.4 Pediatric Use The safety and efficacy of KYMRIAH have been established in pediatric patients . Use of KYMRIAH is supported by a single-arm trial [ see Clinical Studies ( 14 ) in the full prescribing information ] that included 52 pediatric patients with relapsed or refractory B-cell precursor ALL in the following age groups : 33 children ( age 3 years to less than 12 years ) and 19 adolescents ( age 12 years to less than 17 years ). No differences in efficacy or safety were observed between the different age subgroups or in comparison to the young adults in the trial .
8.5 Geriatric Use The safety and effectiveness of KYMRIAH have not been established in geriatric patients . Clinical studies of KYMRIAH for this indication did not include patients age 65 years and over .
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Medication Guide ).
Ensure that patients understand the risk of manufacturing failure . This has been reported in up to 9 % of manufacturing attempts . In case of a manufacturing failure , a second manufacturing of KYMRIAH may be attempted . In addition , while the patient awaits the product , additional chemotherapy ( not the lymphodepletion ) may be necessary and may increase the risk of adverse events during the pre-infusion period .
Prior to infusion , advise patients of the following risks :
• Cytokine Release Syndrome ( CRS ) -- Report signs and symptoms of CRS ( high fever , difficulty breathing , chills / shaking chills , severe nausea , severe vomiting , severe diarrhea , severe muscle pain , severe joint pain , very low blood pressure , or dizziness / lightheadedness ) to their healthcare professional [ see Warnings and Precautions ( 5.1 ), Adverse Reactions ( 6.1 )].
• Neurological Toxicities -- Report altered or decreased consciousness , delirium , confusion , agitation , seizures , difficulty speaking and understanding , or loss of balance to their healthcare professional [ see Warnings and Precautions ( 5.2 ), Adverse Reactions ( 6.1 )].
• Serious Infections -- KYMRIAH may cause serious infections . Advise patients that they will be screened for HBV , HCV , and HIV before collection of cells [ see Warnings and Precautions ( 5.5 ), Adverse Reactions ( 6.1 )].
• Hypogammaglobulinemia -- Patients may need to receive immunoglobulin replacement for an indefinite amount of time following treatment with KYMRIAH . Patients should tell their physician about their treatment with KYMRIAH before receiving a live virus vaccine [ see Warnings and Precautions ( 5.7 ), Adverse Reactions ( 6.1 )].
• Driving and Engaging in Hazardous Occupations -- Patients should refrain from driving and engaging in hazardous occupations or activities , such as operating heavy or potentially dangerous machinery , for at least 8 weeks after treatment [ see Warnings and Precautions ( 5.9 )].
Patients should be instructed to contact Novartis Pharmaceuticals Corporation at 1-844-4KYMRIAH if they get secondary malignancies [ see Warnings and Precautions ( 5.8 )].
Distributed by : Novartis Pharmaceuticals Corporation East Hanover , New Jersey 07936
© Novartis T2017-78
0.87-0.98 ; p < 0.01 ).
Compared with whites , African- Americans ( HR = 0.86 ) and Asians ( HR = 0.88 ) had superior OS ( p < 0.001 ). Significant differences in OS were observed during various time points , but not during the most recent years ( 2006-2010 ), which made the linear trend of OS for all races non-significant over the total study duration ( p = 0.182 ).
The following factors were associated with inferior median OS :
• increased age ( HR = 1.17 ; p < 0.001 )
• female sex ( HR = 0.96 ; p = 0.006 )
• earlier year of diagnosis ( HR for 2006-2010 = 0.51 [ reference category = 1991-1995 ]; p < 0.001 )
Of the MDEs , hypercalcemia ( HR = 1.61 ; p < 0.001 ), renal dysfunction ( HR = 1.19 ; p < 0.001 ), and bone fractures ( HR = 1.34 ; p < 0.001 ) were associated with inferior survival .
Almost one-third of patients ( 32.4 %) had a Medicare claim related to anti-MM therapies or hematopoietic cell transplantation ( HCT ). Overall treatment increased significantly from 29.6 percent in 2003 and 2004 to 63.1 percent in 2009 and 2010 ( p < 0.001 ), likely related to the “ dramatic ” increase in the use of immunomodulatory drugs ( IMiDs ) and steroids between 2003 to 2004 and 2009 to 2010 ( 9.5 % vs . 29.4 % for IMiDs [ p < 0.001 ] and 21.5 % vs . 499.6 % for steroids [ p < 0.001 ]).
HCT use increased over time , reaching 14.2 percent in 2009 to 2010 . “ This increase in HCT use in the Medicare population is likely because of improved supportive care measures as well as earlier treatment for MM leading to the prevention of organ dysfunction and , hence , eligibility for HCT despite patient age in several cases ,” the researchers explained . They also observed a “ sharp increase ” in lenalidomide use , which was considered an expected trend .
“ A better understanding and accounting for these factors will ensure that all patients , irrespective of sociodemographic factors , receive benefit from novel therapeutics , health-care access , and health-care use ,” the authors concluded .
The study is limited by its reliance on claims-based data , which may have inaccurate or missing information . ● Dr . Ailawadhi reports financial support from Pharmacyclics , Takeda , Amgen , and Novartis .
REFERENCE
Ailawadhi S , Frank RD , Sharma M , et al . Trends in multiple myeloma presentation , management , cost of care , and outcomes in the Medicare population : a comprehensive look at racial disparities . Cancer . 2018 January 23 . [ Epub ahead of print ]
ASH Clinical News 31
CLINICAL NEWS lowest among Asians ($630; ranges not reported; p=0.009) but increased most steadily among Hispanics (p<0.001). Drug claims any time after an MM diagnosis were highest among Hispanics ($5,400), followed by Asians ($4,700), African-Americans ($3,900), and whites ($3,300; p<0.001). African-American patients also had the highest number of total claims (p<0.001). “These differences are not clearly explained by disease presentation or complications, because the patterns are not similar to our analysis of MDEs in these patients,” the researchers noted. In the entire population, overall survival (OS) was 21 percent at five years, 6 percent at 10 years, and 2 percent at 15 years. People with B:7.75” higher median incomes T:7.5” experienced bet- (>$61,600 vs. ≤$34,700) ter OS (hazard ratio S:7” [HR] = 0.92; 95% CI Metabolism and nutrition disorders: tumor lysis syndrome (6%) Vascular disorders: capillary leak syndrome (3%) Laboratory Abnormalities Selected laboratory abnormalities worsening from baseline Grade 0-2 to Grade 3-4 are shown in Table 3. Table 3. Selected Other Laboratory Abnormalities Worsening from Baseline Grade 0-2 to Grade 3-4 Following Treatment with KYMRIAH based on CTCAE a (N=68) Grade 3 or 4 (%) Increased Aspartate Aminotransferase 28 Hypokalemia 27 Increased Alanine Aminotransferase 21 Increased bilirubin 21 Hypophosphatemia 19 a CTCAE = Common Terminology Criteria for Adverse Events version 4.03 All patients experienced neutropenia, anemia and thrombocytopenia. See Table 4 for the incidences of Grade 3 and Grade 4 prolonged thrombocyto - penia and prolonged neutropenia in responding patients. Table 4. Prolonged Cytopenias Following Treatment with KYMRIAH N=52 (%) Day 28 Day 56 Prolonged neutropenia a 40 17 Prolonged thrombocytopenia a 27 12 a Grade 3 and 4 observed within 14 days after Day 28 or Day 56 in responding patients 7 DRUG INTERACTIONS HIV and the lentivirus used to make KYMRIAH have limited, short spans of identical genetic material (RNA). Therefore, some commercial HIV nucleic acid test (NAT) tests may yield false-positive results in patients who have received KYMRIAH. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no available data with KYMRIAH use in pregnant women. No ani- mal reproductive and developmental toxicity studies have been conducted with KYMRIAH to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known if KYMRIAH has the potential to be transferred to the fetus. 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