SPOTLIGHT
Have other efforts to increase representation of racial minorities in trials and the hematology workforce been successful ? What challenges remain ? Dr . Weeks : The ASH Minority Recruitment Initiative is a program designed to provide funding to help people navigate through a hematology career , recognizing that different expenses mean different things to people from different backgrounds . Different people have more or less disposable income and financial
DARZALEX FASPRO ® ( daratumumab and hyaluronidase-fihj ) injection
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown . All pregnancies have a background risk of birth defect , loss , or other adverse outcomes . In the U . S . general population , the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 % to 4 % and 15 % to 20 %, respectively .
The combination of DARZALEX FASPRO and lenalidomide , thalidomide or pomalidomide is contraindicated in pregnant women , because lenalidomide , thalidomide and pomalidomide may cause birth defects and death of the unborn child . Lenalidomide , thalidomide and pomalidomide are only available through a REMS program . Refer to the lenalidomide , thalidomide or pomalidomide prescribing information on use during pregnancy .
Clinical Considerations
Fetal / Neonatal Adverse Reactions Immunoglobulin G1 ( IgG1 ) monoclonal antibodies are transferred across the placenta . Based on its mechanism of action , DARZALEX FASPRO may cause depletion of fetal CD38 positive immune cells and decreased bone density . Defer administering live vaccines to neonates and infants exposed to daratumumab in utero until a hematology evaluation is completed .
Data
Animal Data DARZALEX FASPRO for subcutaneous injection contains daratumumab and hyaluronidase . Mice that were genetically modified to eliminate all CD38 expression ( CD38 knockout mice ) had reduced bone density at birth that recovered by 5 months of age . Data from studies using CD38 knockout animal models also suggest the involvement of CD38 in the regulation of humoral immune responses ( mice ), feto-maternal immune tolerance ( mice ), and early embryonic development ( frogs ).
No systemic exposure of hyaluronidase was detected in monkeys given 22,000 U / kg subcutaneously ( 12 times higher than the human dose ) and there were no effects on embryo-fetal development in pregnant mice given 330,000 U / kg hyaluronidase subcutaneously daily during organogenesis , which is 45 times higher than the human dose .
There were no effects on pre- and post-natal development through sexual maturity in offspring of mice treated daily from implantation through lactation with 990,000 U / kg hyaluronidase subcutaneously , which is 134 times higher than the human doses .
Lactation Risk Summary There is no data on the presence of daratumumab and hyaluronidase in human milk , the effects on the breastfed child , or the effects on milk production . Maternal immunoglobulin G is known to be present in human milk . Published data suggest that antibodies in breast milk do not enter the neonatal and infant circulations in substantial amounts . Because of the potential for serious adverse reactions in the breastfed child when DARZALEX FASPRO is administered with lenalidomide , thalidomide or pomalidomide , advise women not to breastfeed during treatment with DARZALEX FASPRO . Refer to lenalidomide , thalidomide or pomalidomide prescribing information for additional information .
Data
Animal Data No systemic exposure of hyaluronidase was detected in monkeys given 22,000 U / kg subcutaneously ( 12 times higher than the human dose ) and there were no effects on post-natal development through sexual maturity in offspring of mice treated daily during lactation with 990,000 U / kg hyaluronidase subcutaneously , which is 134 times higher than the human doses .
Females and Males of Reproductive Potential DARZALEX FASPRO can cause fetal harm when administered to a pregnant woman [ see Use in Specific Populations ].
Pregnancy Testing With the combination of DARZALEX FASPRO with lenalidomide , thalidomide or pomalidomide , refer to the lenalidomide , thalidomide or pomalidomide labeling for pregnancy testing requirements prior to initiating treatment in females of reproductive potential .
Contraception Advise females of reproductive potential to use effective contraception during treatment with DARZALEX FASPRO and for 3 months after the last dose . Additionally , refer to the lenalidomide , thalidomide or pomalidomide labeling for additional recommendations for contraception .
Pediatric Use Safety and effectiveness of DARZALEX FASPRO in pediatric patients have not been established .
Geriatric Use Of the 291 patients who received DARZALEX FASPRO as monotherapy for relapsed and refractory multiple myeloma , 37 % were 65 to < 75 years of age , and 19 % were 75 years of age or older . No overall differences in effectiveness of DARZALEX FASPRO have been observed between patients ≥65 years of age and younger patients . Adverse reactions that occurred at a higher frequency ( ≥5 % difference ) in patients ≥65 years of age included upper respiratory tract infection , urinary tract infection , dizziness , cough , dyspnea , diarrhea , nausea , fatigue , and peripheral edema . Serious adverse reactions that occurred at a higher frequency ( ≥2 % difference ) in patients ≥65 years of age included pneumonia . responsibility with family .
In terms of recruitment into clinical trials , having legislative bodies mandate inclusion of minorities in studies – or provide a valid explanation as to why they are not included – is important . However , there are several industry-sponsored clinical trials that are not subject to the same regulations . Future work must focus on ensuring that , at the outset , studies consider the impact of racial / ethnic representation
DARZALEX FASPRO ® ( daratumumab and hyaluronidase-fihj ) injection
Of the 214 patients who received DARZALEX FASPRO as combination therapy with pomalidomide and dexamethasone or DARZALEX FASPRO as combination therapy with lenalidomide and low-dose dexamethasone for relapsed and refractory multiple myeloma , 43 % were 65 to < 75 years of age , and 18 % were 75 years of age or older . No overall differences in effectiveness were observed between patients ≥65 years ( n = 131 ) and < 65 years ( n = 85 ). Adverse reactions occurring at a higher frequency ( ≥5 % difference ) in patients ≥65 years of age included fatigue , pyrexia , peripheral edema , urinary tract infection , diarrhea , constipation , vomiting , dyspnea , cough , and hyperglycemia . Serious adverse reactions occurring at a higher frequency ( ≥2 % difference ) in patients ≥65 years of age included neutropenia , thrombocytopenia , diarrhea , anemia , COVID-19 , ischemic colitis , deep vein thrombosis , general physical health deterioration , pulmonary embolism , and urinary tract infection .
Of the 193 patients who received DARZALEX FASPRO as part of a combination therapy for light chain ( AL ) amyloidosis , 35 % were 65 to < 75 years of age , and 10 % were 75 years of age or older . Clinical studies of DARZALEX FASPRO as part of a combination therapy for patients with light chain ( AL ) amyloidosis did not include sufficient numbers of patients aged 65 and older to determine whether effectiveness differs from that of younger patients . Adverse reactions that occurred at a higher frequency in patients ≥65 years of age were peripheral edema , asthenia , pneumonia and hypotension .
No clinically meaningful differences in the pharmacokinetics of daratumumab were observed in geriatric patients compared to younger adult patients [ see Clinical Pharmacology ( 12.3 ) in Full Prescribing Information ].
REFERENCES
1 . Chapuy , CI , RT Nicholson , MD Aguad , et al ., 2015 , Resolving the daratumumab interference with blood compatibility testing , Transfusion , 55:1545-1554 ( accessible at http :// onlinelibrary . wiley . com / doi / 10.1111 / trf . 13069 / epdf ).
PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Patient Information ).
Hypersensitivity and Other Administration Reactions Advise patients to seek immediate medical attention for any of the following signs and symptoms of systemic administration-related reactions : itchy , runny or blocked nose ; chills , nausea , throat irritation , cough , headache , shortness of breath or difficulty breathing [ see Warnings and Precautions ].
Cardiac Toxicity in Patients with Light Chain ( AL ) Amyloidosis
Advise patients to immediately contact their healthcare provider if they have signs or symptoms of cardiac adverse reactions [ see Warnings and Precautions ].
Neutropenia Advise patients to contact their healthcare provider if they have a fever [ see Warnings and Precautions ].
Thrombocytopenia Advise patients to contact their healthcare provider if they have bruising or bleeding [ see Warnings and Precautions ].
Embryo-Fetal Toxicity Advise pregnant women of the potential hazard to a fetus . Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [ see Warnings and Precautions , Use in Specific Populations ].
Advise females of reproductive potential to avoid becoming pregnant during treatment with DARZALEX FASPRO and for 3 months after the last dose [ see Use in Specific Populations ].
Advise patients that lenalidomide , thalidomide and pomalidomide have the potential to cause fetal harm and have specific requirements regarding contraception , pregnancy testing , blood and sperm donation , and transmission in sperm . Lenalidomide , thalidomide and pomalidomide are only available through a REMS program [ see Use in Specific Populations ].
Interference with Laboratory Tests Advise patients to inform their healthcare provider , including personnel at blood transfusion centers , that they are taking DARZALEX FASPRO , in the event of a planned transfusion [ see Warnings and Precautions ].
Advise patients that DARZALEX FASPRO can affect the results of some tests used to determine complete response in some patients and additional tests may be needed to evaluate response [ see Warnings and Precautions ].
Hepatitis B Virus ( HBV ) Reactivation Advise patients to inform healthcare providers if they have ever had or might have a hepatitis B infection and that DARZALEX FASPRO could cause hepatitis B virus to become active again [ see Adverse Reactions ].
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as a potential variable of interest and that study findings are applicable to diverse populations .
Dr . Barabino : In my view , the biggest challenge is mistrust of research , research institutions , and investigators , along with mistrust of physicians and healthcare providers . As researchers and practitioners , we have a responsibility to build trust and eliminate racial bias . Mistrust has deep historical roots steeped in racism for racially minoritized and indigenous people . The path forward to building trust will not be easy , but success on that path has wide-ranging implications for better representation and improved health outcomes .
What do you hope that attendees will take away from this session ? Dr . Barabino : From my presentation , I hope that attendees gain a better appreciation for the role that racial bias in science and medicine plays in who conducts research , how research is conducted , and who benefits from it . I also want the audience to think about what ’ s needed to avoid bias and improve study design and outcomes .
Dr . Weeks : The goal of this session is to continue to stimulate conversations about these topics . We need people to feel comfortable sitting with , standing up , and speaking out about ways to implement structural changes . To get there , we have to educate them about the basic principles of what race is , what structural racism is , and the sequelae . This Scientific Session and the anti-racism track that we have at this year ’ s meeting are a good start . Hopefully attendees can go into their communities and start to implement change .
Special Scientific Session on Race and Science
Wednesday , December 8 , 2021 , 4:00 p . m . - 4:45 p . m . Georgia World Congress Center , Hall C2-C3
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ASH Clinical News 35