MAGNETISMM-2: Study of Elranatamab (PF-06863135) in Japanese Participants With Multiple Myeloma

An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious adverse events. An SAE was defined as any untoward medical occurrence that, at any dose resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or that was considered as an important medical event. A TEAE was defined as an AE that first occurred from the first dose of the study intervention until 90 days after the last dose or the day before starting a new anticancer therapy, whichever occurred first. Treatment related AEs and SAEs were defined as AEs and SAEs which was related to the treatment.

CTCAEv5.0 G3:severe/clinically significant;G4:life-threatening;G5:death.ASTCT CRS G3:temp>=38degC,hypotension required vasopressor with/without vasopressin and/or hypoxia required high-flow nasal cannula,facemask,nonrebreather mask or venturi mask;G4:temp>=38degC,hypotension required multiple vasopressors(excluding vasopressin)and/or hypoxia required positive pressure;G5:death.ICANS G3:ICE score0-2,awakens only to tactile stimulus,clinical seizure focal/generalized resolves rapidly or nonconvulsive seizures on electroencephalography resolve with intervention,focal/local edema on neuroimaging;G4:ICEscore 0(unarousable unable to perform ICE),unarousable or requires vigorous/repetitive tactile stimuli to arouse,stupor/coma,life-threatening prolonged seizure(>5 min),repetitive clinical/electrical seizure without return to baseline,deep focal motor weakness,diffuse cerebral edema on neuroimaging,decerebrate/decorticate posturing,cranial nerve VI palsy,papilledema,Cushing's triad;G5:death.

Hematology parameters that were assessed included: Anemia, Lymphocyte count decreased, Neutrophil count decreased, Platelet count decreased, White blood cell decreased. Abnormalities were graded based on National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 - Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.

Chemistry parameters that were assessed included: Alanine aminotransferase increased, Alkaline phosphatase increased, Aspartate aminotransferase increased, Blood bilirubin increased, Creatinine increased, Hypercalcemia, Hyperkalemia, Hypermagnesemia, Hypernatremia, Hypoalbuminemia, Hypocalcemia, Hypoglycemia, Hypokalemia, Hypomagnesemia, Hyponatremia. Abnormalities were graded based on CTCAE version 5.0- Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.

Area under the concentration-time profile from time zero to the time tau where the dosing interval (tau = 1 week). AUCtau was determined using the linear/log trapezoidal method.

'A participant was considered ADA positive if baseline titer was missing or negative and participant had >=1 post-treatment positive titer, or positive titer at baseline and had a >=4-fold increase in titer from baseline in >=1 post-treatment sample.

Titers of ADA at specified timepoints were reported in this outcome measure.

A participant was considered NAb positive if baseline titer was missing or negative and participant had >=1 post-treatment positive titer, or positive titer at baseline and had a >=4-fold increase in titer from baseline in >=1 post-treatment sample.

ORR:% of participants with best overall response; confirmed stringent complete response(sCR),CR, very good partial response(VGPR) or PR per International Myeloma Working Group criteria.sCR: CR\& normal serum free light chain(sFLC)ratio \&absence of clonal cells in BMB/BMA by immunohistochemistry, immunofluorescence or flow cytometry.CR: negative immunofixation on serum \&urine, disappearance of soft tissue plasmacytoma \&<5% plasma cells in BMA, if disease measured by sFLC only,preceding criteria plus normal sFLC ratio.VGPR:Serum \& urine M-protein detectable by immunofixation but not on electrophoresis; or >=90% reduction in serum\&urine M-protein level <100mg/24h.PR:>=50% reduction in serum M-protein \& reduction in 24h urinary M-protein by >=90% or <200 mg/24h. If serum \& urine M-protein unmeasurable,VGPR \& PR: >=90% \&>=50% decrease in difference respectively between involved \& uninvolved sFLC levels \& if present at baseline,>=90% \& >=50% reduction in soft tissue plasmacytomas' size.

TTR was defined for participants with confirmed objective response (sCR,CR,VGPR and PR) as the time from first date of study intervention to the date of first documentation of objective response. sCR: CR and normal sFLC ratio with absence of clonal cells in BMB/BMA by immunohistochemistry, immunofluorescence or flow cytometry.CR: negative immunofixation on serum and urine,disappearance of soft tissue plasmacytoma, <5% plasma cells in BMA, if disease measured by sFLC only,preceding criteria plus normal sFLC ratio.VGPR:Serum and urine M-protein detectable by immunofixation but not on electrophoresis; or >=90% reduction in serum and urine M-protein level <100mg/24h.PR:>=50% reduction in serum M-protein and reduction in 24h urinary M-protein by >=90% or <200 mg/24h.If serum and urine M-protein unmeasurable,VGPR \& PR: >=90%,>=50% decrease in difference respectively between involved and uninvolved sFLC levels,if present at baseline,>=90%, >=50% reduction in soft tissue plasmacytomas' size.

DOR: time from first documentation of objective response subsequently confirmed, until first documentation of confirmed PD or death due to any cause, whichever occurred first. PD= increase of >=25% from lowest value in >=1 of following (serum M-protein [absolute increase >=0.5g/dL]; serum M-protein increase >=1g/dL [when lowest M-protein >=5g/dL]; urine M-protein [absolute increase >=200mg/24h]; participants without measurable serum \& urine M-protein levels, difference between involved \& uninvolved sFLC levels [absolute increase >10mg/dL]; in participants without measurable serum, urine M-protein levels \& involved sFLC levels: bone marrow plasma-cell % irrespective of baseline status [absolute increase >=10%]; appearance of new lesion,>=50% increase from nadir in SPD of >1 lesion, or >=50% increase in longest diameter of previous lesion >1cm in short axis; >=50% increase in circulating plasma cells [>=200cells/μL] if this is the only measure of disease.

Progression free survival (PFS) was the time from the first date of the study intervention to the date of the first documentation of confirmed progression, or death due to any cause.

Overall survival (OS) was the time from the first date of the study intervention to the date of death due to any cause. Participants not known to have died are censored on the date of last known alive.

MRD negativity rate was defined as percentage of participants with CR or sCR with negative MRD per IMWG sequencing criteria by bone marrow aspirate (BMA). sCR: CR and normal sFLC ratio with absence of clonal cells in BMB/BMA by immunohistochemistry, immunofluorescence or flow cytometry.CR: negative immunofixation on serum and urine, disappearance of soft tissue plasmacytoma and <5% plasma cells in BMA, if disease measured by sFLC only, preceding criteria plus normal sFLC ratio. MRD was reported at threshold frequency of 10^5 and 10^6.