The immunogenicity of LUMOXITI was eva luated using electrochemiluminescent (ECL)-basedimmunoassay to test for anti-moxetumomab pasudotox-tdfk antibodies (ADA). For patients whose serumtested positive for ADA, a cell-based assay was performed to detect neutralizing antibodies (nAb). InStudy 1053, 59% (45/76) of patients tested positive for ADA prior to any treatment with moxetumomabpasudotox-tdfk. Seventy out of 80 subjects tested ADA positive at any point during the study and were
subsequently tested for nAb. The results showed that 67 of 70 subjects were nAb-positive.
Among these67 patients who tested nAb-positive, 99% (66/67) had ADA specific to the PE38 binding domain, and54% (36/67) also had ADA specific to the CD22 binding domain. In 41 out of 73 patients who hadbaseline and post-baseline ADA results, the median fold increase from baseline (Cycle 1, Day 1) in ADAtiter was 3.75- (range: 0 to 240), 54- (range: 0 to 2560), 120- (range: 0 to 1920), and 128- (range: 0 to2560) fold at Cycles 2, 3, 5, and end-of-treatment, respectively. Patients who tested positive for ADA haddecreased systemic moxetumomab pasudotox-tdfk concentrations [see Clinical Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Based on its mechanism of action and findings in non-pregnant female animals, LUMOXITI is expectedto cause maternal and embryo-fetal toxicity when administered to a pregnant woman [see ClinicalPharmacology (12.1) and Nonclinical Toxicology (13.2)].
There are no available data on LUMOXITI usein pregnant women to inform a drug-associated risk of major birth defects and miscarriage.
Animalreproduction or developmental toxicity studies have not been conducted with LUMOXITI.
Advisepregnant women of the potential risk to a fetus.
11 Reference ID: 4320135
The estimated background risk of major birth defects and miscarriage for the indicated population isunknown. All pregnancies have abackground 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 clinicallyrecognized pregnancies is 2-4% and 15-20%, respectively.
8.2 Lactation
Risk Summary
No data are available regarding the presence of moxetumomab pasudotox-tdfk in human milk, the effectson the breastfed child, or the effects on milk production. The developmental and health benefits ofbreastfeeding should be considered along with the mother's clinical need for LUMOXITI and anypotential adverse effects on the breastfed child from LUMOXITI or from the underlying maternalcondition.
8.3 Females and Males of Reproductive Potential
Contraception
Females
To avoid potential exposure to the fetus, women of reproductive potential should use effectivecontraception during treatment with LUMOXITI and for at least 30 days after the last dose is received.
Verify the pregnancy status of females of reproductive potential prior to initiating LUMOXITI.
8.4 Pediatric UseSafety and effectiveness have not been established in pediatric patients.
8.5 Geriatric Use
In the combined safety database of HCL patients treated with LUMOXITI, 31% (40/129) of patientstreated with LUMOXITI were 65 years of age or older and 8% (10/129) were 75 years of age or older.
Exploratory analyses across this population suggest a higher incidence of adverse reactions leading todrug discontinuation (23% versus 7%) and renal toxicity (4 |
