Cohort D will enroll participants with multiple myeloma who have previously received >= 3 prior lines of therapy. Participants will receive talquetamab SC biweekly at a RP2D selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. Participants in this cohort will receive tocilizumab prophylaxis for cytokine release syndrome (CRS) including all outpatient dosing. Participants will transition to OLE upon communication by the sponsor. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the LTE and will continue to receive study treatment.

Cohort E will enroll participants with multiple myeloma who have previously received at least 1 proteasome inhibitor (PI), 1 immunomodulatory imide drug (IMiD), and 1 anti-cluster of differentiation 38 (CD38) monoclonal antibody.

Participants will receive talquetamab SC biweekly at a RP2D selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. Participants will receive tocilizumab prophylaxis for CRS with consolidated priming dose schedules as well as possible transition to outpatient priming dosing transition to OLE upon communication by the sponsor. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the LTE and will continue to receive study treatment.

CR or better rate is defined as the percentage of patients who achieve CR or better according to IMWG response criteria.

sCR rate is defined as the percentage of patients who achieve sCR according to IMWG response criteria.

TTR is defined as the time between date of first dose of study drug and the first efficacy evaluation that the participant has met all criteria for PR or better.

PFS is defined as time from date of first dose of study drug to date of first documented PD, per IMWG criteria, or death due to any cause, whichever occurs first.

OS is defined as the time from the date of first dose of study drug to the date of the participant's death.

MRD negativity rate is measured only for participants who achieve at least a CR but is reported based on all treated similar to the other response data.

An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.

Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). 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.

Number of participants with abnormalities in clinical laboratory values (such as hematology, serum chemistry and coagulation) will be reported.

Serum samples will be analyzed to determine concentrations of talquetamab.

Antibodies to talquetamab will be assessed to evaluate potential immunogenicity.

The EORTC- QLQ-Core-30 includes 30 items that make up 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, and nausea/vomiting), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The recall period is 1 week ("past week") and responses are reported using a verbal and numeric rating scales. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.

The EQ-5D-5L is a generic measure of health status. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). The scores for the 5 separate questions are categorical and cannot be analyzed as cardinal numbers.

The PGIS is a single item that assesses severity of the participant's health state, on a 5-point verbal rating scale. Score ranges from 1 (None) to 5 (Very Severe).

ORR in participants with high risk is defined as the overall response rate among the high risk molecular subgroups or other high-risk molecular subtypes.