A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-Cell Maturation Antigen (BCMA) in Participants With Relapsed or Refractory Multiple Myeloma

An AE was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Severity was graded according to the NCI-CTCAE version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.

Maximum observed plasma concentration (Cmax) of JNJ-68284528 transgene was reported. Cmax was calculated in copies per microgram (mcg) genomic deoxyribonucleic acid (DNA).

Tlast was defined as actual sampling time of last measurable (non-below quantification limit [BQL]) analyte concentration of JNJ-68284528 transgene.

Area under the plasma concentration versus time curve from time 0 to last measurable concentration of JNJ-68284528 transgene was reported.

Area under the plasma concentration versus time curve from time 0 to infinite time of JNJ-68284528 transgene was reported.

Maximum observed plasma concentration (Cmax) of CD3+CAR+ Cells was reported. Cmax was calculated in cells per microliter.

T Cell persistence after a single infusion of JNJ-68284528 was reported. T Cell persistence was defined as actual sampling time of last measurable (non-below quantification limit [BQL]) analyte concentration.

Area under the plasma concentration versus time curve from time 0 to last measurable concentration of CD3+CAR+ Cells was reported.

Area under the plasma concentration versus time curve from time 0 to infinite time of CD3+CAR+ Cells in blood after a single infusion of JNJ-68284528 was reported.

Mean concentration of soluble BCMA levels in serum after single infusion of JNJ-68284528 were reported.

Number of participants with depletion of BCMA expressing cells were reported.

Serum systemic cytokine concentrations (Interleukin [IL]-6, IL-10, and Interferon Gamma [IFN-g]) were reported.

Cmax of CAR-T cells (CD3+CAR+ cells in blood) after a single infusion of JNJ-68284528 was reported.

Maximum T cell expansion was defined as maximum observed plasma concentration (Cmax) after a single Infusion of JNJ-68284528.

Percentage of participants with positive antibodies to JNJ-68284528 were reported.

VGPR or better response rate was defined as the percentage of participants who achieved VGPR or complete response (CR) (including stringent complete response [sCR]) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or >= 90% reduction in serum M-protein plus urine M-protein level less than (<) 100 mg/24 hour; CR: negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <5% PCs in bone marrow; sCR: CR in addition to having a normal free light chain (FLC) ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry.

MRD negativity rate was defined as percentage of participants who had negative MRD by bone marrow aspirate at any timepoint after initial dose of JNJ-68284528 and before disease progression or starting subsequent therapy or retreatment with JNJ-68284528. MRD negativity rate was assessed by next-generation sequencing at a threshold of <10^5.

Clinical benefit rate was defined as the percentage of participants with best response of minimal response (MR) or better (including sCR, CR, VGPR, PR, and MR). MR was defined as >=25% but less than or equal to (<=) 49% reduction of serum M-protein and reduction in 24-hour urine M-protein by 50% to 89%. In addition to the above criteria, if present at baseline, >=50% reduction in the size of soft tissue plasmacytomas was also required.

DOR was defined as the time (in months) from the date of initial documented response (PR or better response) to the date of first documented evidence of progressive disease (PD) or death. PD is defined as an increase of 25% from the lowest response value in one of the following: serum and urine M-component (absolute increase must be >=0.5 gram per deciliter [g/dL] and >=200 mg/24 hours respectively); only in participants without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be >10 mg/dL); definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder, appearance of a new lesion(s), >=50% increase in circulating plasma cells if this was the only measure of disease.

Time to first response was defined as the time between date of the initial infusion of JNJ-68284528 and the first efficacy evaluation that the participant met all criteria for PR or better. IMWG criteria for PR: >=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or <200 mg per 24 hours, If the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow PCs is required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%. In addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.

Progression-free survival was defined as the time from the date of the initial infusion of JNJ-68284528 to the date of first documented disease progression.

Overall survival was defined as the time from the date of the initial infusion of JNJ-68284528 to the date of the participant's death.

EQ-5D-5L was a 5-item questionnaire consisted of 2 components: a health state profile/a single utility index value and an optional VAS. EQ-5D health state profile/a single utility index value had 5 dimensions including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension had 5 response levels: 1 =no problems, 2 =slight problems, 3 =moderate problems, 4 =severe problems and 5 =extreme problems. The scores for the 5 dimensions were used to compute a single utility score ranging from 0 to 1 representing the general health status of the individual. Higher score indicated better health status. EQ-5D VAS was used to record participant's rating for his/her "health today" and ranging from 0 to 100, where 0 = worst imaginable health state and 100 = best imaginable health state.

EQ-5D-5L was a 5-item questionnaire consisted of 2 components: a health state profile/a single utility index value and an optional VAS. EQ-5D health state profile/a single utility index value had 5 dimensions including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension had 5 response levels: 1 =no problems, 2 =slight problems, 3 =moderate problems, 4 =severe problems and 5 =extreme problems. The scores for the 5 dimensions were used to compute a single utility score ranging from 0 to 1 representing the general health status of the individual. Higher score indicated better health status. EQ-5D VAS was used to record participant's rating for his/her "health today" and ranging from 0 to 100, where 0 = worst imaginable health state and 100 = best imaginable health state.

EQ-5D-5L was a 5-item questionnaire consisted of 2 components: a health state profile/a single utility index value and an optional VAS. EQ-5D health state profile/a single utility index value had 5 dimensions including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension had 5 response levels: 1 =no problems, 2 =slight problems, 3 =moderate problems, 4 =severe problems and 5 =extreme problems. The scores for the 5 dimensions were used to compute a single utility score ranging from 0 to 1 representing the general health status of the individual. Higher score indicated better health status. EQ-5D VAS was used to record participant's rating for his/her "health today" and ranging from 0 to 100, where 0 =worst imaginable health state and 100 = best imaginable health state.

EQ-5D-5L was a 5-item questionnaire consisted of 2 components: a health state profile/a single utility index value and an optional VAS. EQ-5D health state profile/a single utility index value had 5 dimensions including mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension had 5 response levels: 1 =no problems, 2 =slight problems, 3 =moderate problems, 4 =severe problems and 5 =extreme problems. The scores for the 5 dimensions were used to compute a single utility score ranging from 0 to 1 representing the general health status of the individual. Higher score indicated better health status. EQ-5D VAS was used to record participant's rating for his/her "health today" and ranging from 0 to 100, where 0 = worst imaginable health state and 100 = best imaginable health state.

EORTC QLQ-C30 was a 30 items self-reporting questionnaire, with 1 week recall period, resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status scale (GHS), 3 symptom scales (fatigue, nausea and vomiting, and pain) and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Questionnaire includes 28 items with 4-point Likert type responses from "1-not at all" to "4-very much" to assess functioning and symptoms;2 items with 7-point Likert scales (1= poor and 7= excellent) for global health and overall health related QoL. Scores are transformed to 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms. Negative change from baseline values shows deterioration in quality of life or functioning and reduction in symptom and positive values indicate improvement and worsening of symptoms.

EORTC QLQ-C30 was a 30 items self-reporting questionnaire, with 1 week recall period, resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status scale (GHS), 3 symptom scales (fatigue, nausea and vomiting, and pain) and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Questionnaire includes 28 items with 4-point Likert type responses from "1-not at all" to "4-very much" to assess functioning and symptoms;2 items with 7-point Likert scales (1= poor and 7= excellent) for global health and overall health related QoL. Scores are transformed to 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms. Negative change from baseline values shows deterioration in quality of life or functioning and reduction in symptom and positive values indicate improvement and worsening of symptoms.

PGIS was a single item to assess severity of pain on a 5-point verbal rating scale ranged from 1 (no pain) to 5 (very severe pain), where 1: none; 2: mild; 3: moderate; 4: severe; 5: very severe. A higher score indicated a more severe pain.

PGIC was a single item to assess the participant's perception in change of their overall health status using a 7-point verbal rating scale ranging from 1(a lot better now) to 7 (a lot verse now), where 1: a lot better now; 2: moderately better now; 3: a little better now; 4: neither better nor worse; 5: a little worse now; 6: moderately worse now; 7: a lot worse now. Higher score indicated worse health status.

EORTC QLQ-MY20 scale comprised of 20 questions that addressed four myeloma-specific HRQoL domains: disease symptoms (includes bone aches or pain, back pain, hip pain, arm or shoulder pain, chest pain, and pain increasing with activity), side effects of treatment (includes drowsiness, thirst, feeling ill, dry mouth, hair loss, upset by hair loss, tingling hands or feet, restlessness/agitation, acid indigestion/heartburn, and burning or sore eyes), future perspective (includes worry about death and health in the future, and thinking about illness) and body image. The scale was administered to assess 4 single items: feel restless or agitated, thinking about your illness, worried about dying, worried about health in the future. Scores were averaged and scales were transformed on a 0 to 100 scale. A high score for side effects of treatment represented a high level of symptomatology or problems, whereas a high score for future perspective represented better outcomes.

EORTC QLQ-MY20 scale comprised of 20 questions that addressed four myeloma-specific HRQoL domains: disease symptoms (includes bone aches or pain, back pain, hip pain, arm or shoulder pain, chest pain, and pain increasing with activity), side effects of treatment (includes drowsiness, thirst, feeling ill, dry mouth, hair loss, upset by hair loss, tingling hands or feet, restlessness/agitation, acid indigestion/heartburn, and burning or sore eyes), future perspective (includes worry about death and health in the future, and thinking about illness) and body image. The scale was administered to assess 4 single items: feel restless or agitated, thinking about your illness, worried about dying, worried about health in the future. Scores were averaged and scales were transformed on a 0 to 100 scale. A high score for side effects of treatment represented a high level of symptomatology or problems, whereas a high score for future perspective represented better outcomes.