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

Inclusion Criteria:

• Cohort A: Received a minimum of 1 to a maximum of 3 prior lines of therapy includinga proteasome inhibitor (PI) and immunomodulatory therapy (IMiD), and lenalidomiderefractory per International Myeloma Working Group (IMWG) guidelines

• Cohort B: Received one line of prior therapy including a PI and an IMiD, and diseaseprogression per IMWG criteria less than or equal to (<=) 12 months after treatmentwith autologous stem cell transplantation (ASCT) or <=12 months from the start ofanti-myeloma therapy for participants who have not had an ASCT

• Cohort C: Previously treated with a PI, an IMiD, an anti-CD38 monoclonal antibodyand B-cell maturation antigen (BCMA)-directed therapy

• Cohort D: Newly diagnosed multiple myeloma per IMWG with a history of 4 to 8 totalcycles of initial therapy, including induction, high-dose therapy, and ASCT with orwithout consolidation

• Cohort E: Have newly diagnosed multiple myeloma without prior therapy (one cycle ofprior therapy before enrollment is acceptable) and classified as high risk definedas either: 1) International Staging System (ISS) stage III criteria, Beta 2microglobulin greater than or equal to (>=) 5.5 milligrams per liter (mg/L) (vialocal or central laboratory assessment) or 2) high risk cytogenetic featuresdel(17/17p), t (14;16), t(14;20), 1q amplification (at least 4 total copies) in atleast 20 percent (%) of the total plasma cell population

• Cohort F:

• Participant must have a documented efficacy response of very good partial response (VGPR) or better, without progressive disease prior to enrollment, as assessed perIMWG 2016 criteria

• Received initial therapy as specified below. The dose/schedule of cyclesadministered will be as per standard of care. It is acceptable for up to 1 cycle ofthe protocol-specified regimens to be missing one of the listed agents (example,held due to toxicity). Acceptable combinations include: At least 5 to 8 cycles ofinitial therapy with daratumumab, bortezomib, lenalidomide and dexamethasone (D-VRd). The dose/schedule of cycles administered will be as per standard of careor; at least 4 to 8 cycles of initial therapy with daratumumab, lenalidomide anddexamethasone (D-Rd) or; at least 4 to 8 cycles of initial therapy with acarfilzomib-based triplet or quadruplet regimen

• Cohort G: Not considered for high-dose chemotherapy with autologous stem celltransplantation (ASCT) due to: a) Ineligibility due to advanced age; or b)Ineligibility due to presence of comorbid condition(s) likely to have a negativeimpact on tolerability of high-dose chemotherapy with ASCT; or c) Subject refusal ofhigh-dose chemotherapy with ASCT as initial treatment

• Cohort H: Considered a candidate for high-dose chemotherapy with ASCT as initialtreatment

• Cohorts A, B, C, E, G, H:

• Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 1.0gram per deciliter (g/dL) or urine M-protein level >=200 milligrams (mg)/24 hours

• Light chain multiple myeloma in whom only measurable disease is by serum free lightchain (FLC) levels in the serum: Serum immunoglobulin FLC >=10 mg/dL and abnormalserum immunoglobulin kappa lambda FLC ratio

• Cohort A: For participants with neither serum nor urine measurable disease, baselinepositron emission tomography/ computed tomography (PET/CT) or whole -body magneticresonance imaging (MRI) may be used to satisfy the measurable disease criteria. Aminimum of one lesion with a bi-dimensional measurement of at least 1 centimeter (cm)*1 cm is required

• Cohorts B, C: For participants with neither serum nor urine measurable disease,baseline positron emission tomography/ computed tomography (PET/CT) or whole bodymagnetic resonance imaging (MRI) may be used to satisfy the measurable diseasecriteria

• Cohorts A, B, C, D, E, F, G, H: Eastern Cooperative Oncology Group (ECOG)performance status grade of 0 or 1

Exclusion Criteria:

• Cohorts A, B, D, F: Any therapy that is targeted to BCMA

• Cohorts A, B, C, D, F: Prior treatment with chimeric antigen receptor T (CAR-T)therapy directed at any target

• Cohorts A, B, C, D, F:

• Ongoing toxicity from previous anticancer therapy must resolve to baseline levels orto Grade 1 or less except for alopecia or peripheral neuropathy

• Received a cumulative dose of corticosteroids equivalent to >=70 mg of prednisonewithin the 7 days (Cohort A, B, C, F) or 14 days (Cohort D) prior to apheresis

• Serious underlying medical condition, such as (a) evidence of active viral orbacterial infection requiring systemic antimicrobial therapy, or uncontrolledsystemic fungal infection; (b) active autoimmune disease or a history of autoimmunedisease within 3 years; (c) overt clinical evidence of dementia or altered mentalstatus; (d) any history of Parkinson's disease or other neurodegenerative disorder

• Cohorts A, B, C, D, E, F: Known active, or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiplemyeloma

• Cohorts F, G, and H: Active malignancies (that is, progressing or requiringtreatment change in the last 24 months) other than the disease being treated understudy. The only allowed exceptions are: a) non-muscle invasive bladder cancertreated within the last 24 months that is considered completely cured; b) skincancer (non-melanoma or melanoma) treated within the last 24 months that isconsidered completely cured; c) non-invasive cervical cancer treated within the last 24 months that is considered completely cured; d) localized prostate cancer (N0M0):with a Gleason score of greater than or equal to (=>)6, treated within the last 24months or untreated and under surveillance, with a Gleason score of 3+4 that hasbeen treated more than 6 months prior to full study screening and considered to havea very low risk of recurrence, or history of localized prostate cancer and receivingandrogen deprivation therapy and considered to have a very low risk of recurrence,e) breast cancer: adequately treated lobular carcinoma in situ or ductal carcinomain situ, or history of localized breast cancer and receiving antihormonal agents andconsidered to have a very low risk of recurrence; f) malignancy that is consideredcured with minimal risk of recurrence

• Cohorts E, G, and H: Frailty index of >= 2 according to Myeloma Geriatric Assessmentscore