Badanie Elranatamabu (PF-06863135) u chińskich uczestników z opornym na leczenie szpiczakiem mnogim.

BCMA-CD3 bispecific antibody

BCMA-CD3 bispecific antibody

• PF-06863135

Grade(G)4 neutropenia >5 day; febrile neutropenia (absolute neutrophil count [ANC] <1000/millimeter cube (mm^3) with single temperature >38.3 degree Celsius (deg C) or sustained temp>=38 deg C for >1 hour(H); G>=3 neutropenia with infection; G4 thrombocytopenia (unless baseline count >=25,000/mm^3 and <50,000/mm^3, in which case G4 thrombocytopenia to be accompanied by >=G2 bleeding); Platelet count <10,000/mm^3; G3 thrombocytopenia with >=G2 bleeding; G>=4 AE; G3 cytokine release syndrome(CRS) except CRS not maximally treated/improved to <=G1 within 48H; G3 AE except AE attributed to CRS, G3 nausea,vomiting,diarrhea improved to G<=2 within 72H after medical management, G3 fatigue <1 week, G3 AE recovered to baseline/G1 within 5 day; confirmed drug-induced liver injury; G3-4 laboratory (lab) abnormality except G3-4 lab abnormality improved to G<=2 within 72H after medical management & without sequelae;G3 injection site reaction; G2/other clinically important AE may be considered DLT.

ORR: Percentage of participants with best overall response (BOR) of confirmed stringent complete response (sCR), CR, very good partial response (VGPR) or PR per IMWG criteria. sCR: CR and normal serum free light chain (sFLC) ratio and absence of clonal cells in BMB/BMA by IH, IF, or flow cytometry. CR: negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytoma & <5% plasma cells in BMA, if disease measurable 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 M-protein & 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 were 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.

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 and urine M-protein levels, difference between involved and uninvolved sFLC levels [absolute increase >10mg/dL]; in participants without measurable serum, urine M-protein levels and involved sFLC levels: bone marrow plasma-cell percentage 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 >1 cm in short axis; >=50% increase in circulating plasma cells [>=200cells/μL] if this is the only measure of disease.

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 and urine M-protein levels, difference between involved and uninvolved sFLC levels [absolute increase >10mg/dL]; in participants without measurable serum, urine M-protein levels and involved sFLC levels: bone marrow plasma-cell percentage 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 >1 cm in short axis; >=50% increase in circulating plasma cells [>=200cells/μL] if this is the only measure of disease.

CRR: Percentage of participants with BOR of confirmed sCR/CR per IMWG criteria. sCR: CR and normal sFLC ratio and absence of clonal cells in bone marrow biopsy/bone marrow aspiration (BMB/BMA) by immunohistochemistry (IH), immunofluorescence (IF), or flow cytometry. CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytoma and <5% plasma cells in BMA, if disease measurable by sFLC only, preceding criteria plus normal sFLC ratio.

CRR: Percentage of participants with BOR of confirmed sCR/CR per IMWG criteria. sCR: CR and normal sFLC ratio and absence of clonal cells in BMB/BMA by IH, IF, or flow cytometry. CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytoma and <5% plasma cells in BMA, if disease measurable by sFLC only, preceding criteria plus normal sFLC ratio.

ORR: Percentage of participants with best overall response of confirmed sCR, CR, VGPR or PR per IMWG criteria. sCR: CR and normal sFLC ratio and absence of clonal cells in BMB/BMA by IH, IF, or flow cytometry. CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytoma and <5% plasma cells in BMA, if disease measurable 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 M-protein 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 were unmeasurable, VGPR and PR: >=90% and >=50% decrease in difference respectively between involved and uninvolved sFLC levels and if present at baseline, >=90% and >=50% reduction in soft tissue plasmacytomas' size.

DOCR: Time from first documentation of sCR/CR subsequently confirmed, until first documentation of confirmed PD per IMWG criteria 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 and urine M-protein levels, difference between involved and uninvolved sFLC levels [absolute increase >10mg/dL]; in participants without measurable serum, urine M-protein levels and 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.

DOCR: Time from first documentation of sCR/CR subsequently confirmed, until first documentation of confirmed PD per IMWG criteria 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 and urine M-protein levels, difference between involved and uninvolved sFLC levels [absolute increase >10mg/dL]; in participants without measurable serum, urine M-protein levels and 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.

PFS was defined as the time from the date of first dose until confirmed PD per IMWG criteria 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 and urine M-protein levels, difference between involved and uninvolved sFLC levels [absolute increase >10mg/dL]; in participants without measurable serum, urine M-protein levels and 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.

PFS was defined as the time from the date of first dose until confirmed PD per IMWG criteria 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 and urine M-protein levels, difference between involved and uninvolved sFLC levels [absolute increase >10mg/dL]; in participants without measurable serum, urine M-protein levels and 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.

OS was defined as time from date of first dose until death due to any cause. Participants not known to have died were censored on the date of last known alive

TTR, for participants with objective response (OR) per IMWG criteria: time from date of first dose to first documentation of OR that was subsequently confirmed. OR: BOR of confirmed sCR, CR, VGPR or PR. sCR: CR and normal sFLC ratio and absence of clonal cells in BMB/BMA by IH, IF, or flow cytometry. CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytoma & <5% plasma cells in BMA, if disease measured sFLC only, preceding criteria plus normal sFLC ratio. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis/ >=90% reduction in serum M-protein & 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 & uninvolved sFLC levels & if present at baseline, >=90% and >=50% reduction in soft tissue plasmacytomas' size.

TTR, for participants with OR per IMWG criteria: time from date of first dose to first documentation of OR that was subsequently confirmed. OR: BOR of confirmed sCR, CR, VGPR or PR. sCR: CR and normal sFLC ratio and absence of clonal cells in BMB/BMA by IH, IF, or flow cytometry. CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytoma & <5% plasma cells in BMA, if disease measured sFLC only, preceding criteria plus normal sFLC ratio. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis/ >=90% reduction in serum M-protein & 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 & uninvolved sFLC levels & if present at baseline, >=90% and >=50% reduction in soft tissue plasmacytomas' size.

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

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

AE: any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to study intervention. Serious adverse event (SAE): 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. An AE was considered treatment-emergent if it 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. AEs included both SAEs and all other AEs. AEs were graded using CTCAE version 5.0, where Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening; Grade 5: death. Relatedness to study intervention was judged by investigator.

ASTCT CRS Grading: Grade 1: temperature >=38 degree Celsius (deg C) without hypotension or hypoxia; Grade 2: temperature >=38 deg C with hypotension not requiring vasopressors, and/or hypoxia requiring low-flow nasal cannula, facemask or blow-by; Grade 3: temperature >=38 deg C with hypotension requiring a vasopressor with or without vasopressin and/or hypoxia requiring high-flow nasal cannula, high-flow facemask, nonrebreather mask, or Venturi mask; Grade 4: temperature >=38 deg C with hypotension requiring multiple vasopressors (excluding vasopressin) and/or hypoxia requiring positive pressure (e.g., continuous positive airway pressure [CPAP], bilevel positive airway pressure [BiPAP], intubation and mechanical ventilation); Grade 5: death. Number of participants with CRS of any grade is reported in this outcome measure.

ICANS Grade 1: immune effector cell encephalopathy (ICE) score 7-9, participant (P) awakens spontaneously; Grade 2: ICE score 3-6, P awakens to voice; Grade 3: ICE score 0-2, P awakens only to tactile stimulus, any clinical seizure focal or generalized that resolved rapidly/nonconvulsive seizures on electroencephalography that resolved with intervention or focal/local edema on neuroimaging; Grade 4: ICE score 0 (P unarousable and unable to perform ICE), P unarousable/required vigorous/repetitive tactile stimuli to arouse, life-threatening prolonged seizure (>5 minutes), repetitive clinical/electrical seizures without return to baseline in between, deep focal motor weakness, diffuse cerebral edema on neuroimaging; decerebrate/decorticate posturing; cranial nerve VI palsy; papilledema, Cushing's triad; Grade 5: death. ICE: measures alterations in speech, orientation, handwriting, attention and receptive aphasia. Number of participants with ICANS of any grade reported.

A participant was ADA or NAb positive if (1) baseline titer was missing or negative and participant had >= 1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a >= 4-fold dilution increase in titer from baseline in >= 1 post-treatment sample (treatment-boosted).

EORTC QLQ-C30 contains 30 items and is composed of both multi-item scales and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea and vomiting, and pain), 6 single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) and a global health status/QoL scale. Functional scales ranged from 0 (low functioning) to 100 (high functioning) where, higher score= higher levels of functioning. Symptom scales ranged from 0 (no symptoms) to 100 (worse symptoms) where, higher scores= worse symptoms/greater burden. Single item scores ranged from 0 (no problem) to 100 (severe problems) where, higher scores= more severe symptoms/problem. The global health status/QoL also ranged from 0 (low health status/QoL) to 100 (good health status/QoL). Higher scores on the global health status/QoL represent higher health status/quality of life.

EORTC QLQ-MY20 is a myeloma-specific module developed by the EORTC group specifically to assess quality of life in participants with multiple myeloma. It contains 20 items which can be grouped into a disease symptom subscale (6 items), side effects of treatment subscale (10 items), body image (1 item) and future perspective subscale (3 items). The Disease Symptoms and Side Effects of Treatment subscale ranged from 0 (no symptoms/side effects) to 100 (worse symptoms/side effects) with higher scores indicating worse symptoms. The Future Perspective and Body Image subscale ranged from 0 (worst support/functioning) to 100 (best support/functioning) with higher scores indicating better support/functioning (Future Perspective and Body Image).

EORTC QLQ CIPN20 is a module developed by the EORTC group to assess chemotherapy-induced peripheral neuropathy. It contains 20 items which can be grouped into a sensory subscale (9 items), motor subscale (8 items) and autonomic subscale (3 items). Sensory scale scores range from 0 (no sensory symptoms) to 100 (severe sensory symptoms), motor scale scores range from 0 (no motor impairment) to 100 (greater motor impairment), and autonomic scale scores range from 0 (minimal symptoms) to 100 (worse autonomic symptoms). Higher scores indicate worse neuropathy.

EQ-5D-5L consisted of participant completed questionnaire with 2 components: health state profile index and VAS. EQ-5D health state profile index has 5 domains (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), with 5 levels (1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, 5= extreme problems). Responses to 5 dimensions comprised health state index value. E.g. if a participant responds "no problems" for each 5 dimensions, then health state was coded as "11111" with predefined index value to it. EQ-5D-5L index score ranged from -0.594 to 1, UK look-up value was applied to all participants, higher scores indicated better health states. The EQ- VAS measured participant's self-rated health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state) by VAS. higher scores indicated better health states.