Participants with RRMM who are triple-class exposed (previously exposed to at least 1 PI, 1 IMiD, and an anti-CD38 mAb) will receive prophylaxis C along with talquetamab therapy. Participants will start the assigned prophylaxis 7 days before starting talquetamab treatment. After step-up dosing of talquetamab therapy, participants will be treated with talquetamab with prophylaxes for up to 12 months during prophylaxis treatment phase (if there are clinical benefits prophylaxis treatment can continue beyond 12 months, at the treating physician's discretion, after consultation with sponsor). The Talquetamab treatment phase will continue from C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent, discontinuation of talquetamab, or end of study, whichever occurs first.

Participants with RRMM who are triple-class exposed (previously exposed to at least 1 PI, 1 IMiD, and an anti-CD38 mAb) will receive prophylaxis D along with talquetamab therapy. Participants will start the assigned prophylaxis 1 day before starting talquetamab treatment. After step-up dosing of talquetamab therapy, participants will be treated with talquetamab with prophylaxes for up to 12 months during prophylaxis treatment phase (if there are clinical benefits prophylaxis treatment can continue beyond 12 months, at the treating physician's discretion, after consultation with sponsor). The Talquetamab treatment phase will continue from C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent, discontinuation of talquetamab, or end of study, whichever occurs first.

Participants with RRMM who are triple-class exposed (previously exposed to at least 1 PI, 1 IMiD, and an anti-CD38 mAb) will receive single step-up dose of ramantamig subcutaneously followed by the treatment dose until disease progression, death, unacceptable toxicity, withdrawal of consent, discontinuation of ramantamig, or end of study, whichever occurs first.

Prophylaxis A will be administered orally.

Prophylaxis B will be administered orally.

Prophylaxis C will be administered orally.

Prophylaxis D will be administered topically.

Ramantamig will be administered subcutaneously.

Resolution/improvement is defined as 2 potential scenarios: 1) A dysgeusia downgraded to dysgeusia-free, that is (i.e.,) total WETT score of 25th percentile or below at visits prior to the end of month 3 becomes total WETT score above 25th percentile at the end of month 3. 2) Severe dysgeusia downgraded to non-severe dysgeusia, i.e., total WETT score of 10th percentile or below prior to the end of month 3 becomes total WETT score above 10th percentile at the end of month 3. Taste assessment will be performed using taste strips (WETT). Four concentrations will be used for each taste quality: sweet, sour, salty, bitter, & umami. Each test kit contains 53 taste strips; numbered (1 through 53). Participants will use each strip sequentially and record flavor on score card provided. Test will result in maximum (i.e., best) total score of 53. Score will be graded by qualified staff into normative percentile score using provided chart.

Resolution/improvement is defined as 2 potential scenarios: 1) A dysgeusia downgraded to dysgeusia-free, that is (i.e.,) total WETT score of 25th percentile or below at visits prior to the end of month 7 becomes total WETT score above 25th percentile at the end of month 7. 2) Severe dysgeusia downgraded to non-severe dysgeusia, i.e., total WETT score of 10th percentile or below prior to the end of month 7 becomes total WETT score above 10th percentile at the end of month 7. Taste assessment will be performed using taste strips (WETT). Four concentrations will be used for each taste quality: sweet, sour, salty, bitter, & umami. Each test kit contains 53 taste strips; numbered (1 through 53). Participants will use each strip sequentially and record flavor on score card provided. Test will result in maximum (i.e., best) total score of 53. Score will be graded by qualified staff into normative percentile score using provided chart.

Time with dysgeusia is defined as the accumulative days a participant had dysgeusia according to the total WETT score divided by the total days of talquetamab exposure. Taste assessment will be performed using taste strips (WETT). Four concentrations (4=lowest concentration, 1=highest concentration) will be used for each taste quality: sweet, sour, salty, bitter, and umami. Each test kit contains 53 taste strips distributed in 4 packs; and each taste strip is numbered (1 through 53). Participants will use each strip sequentially and record the flavor on a score card provided. The test will result in a maximum (that is, best) total score of 53. The score will be graded by a qualified site staff into a normative percentile score using a provided chart.

Oral toxicity including dysgeusia, oral mucositis, dysphagia, and xerostomia will be graded (including Grade 0 for dysgeusia) based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 5.0. Severity has 5 grades based on CTCAE criteria: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening consequences; and Grade 5: Death.

Oral toxicity including dysgeusia, oral mucositis, dysphagia, and xerostomia will be graded (including Grade 0 for dysgeusia) based on NCI-CTCAE, Version 5.0. Severity has 5 grades based on CTCAE criteria: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening consequences; and Grade 5: Death.

Time to the first onset of treatment-emergent dysgeusia, oral mucositis, dysphagia, or xerostomia, will be reported.

Duration of treatment-emergent oral toxicities including dysgeusia, oral mucositis, dysphagia, and xerostomia will be reported in this outcome measure.

The EORTC-QLQ-C30 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 5 single symptom items (dyspnea, insomnia, appetite loss, constipation, and diarrhea) and a single impact item (financial difficulties). The recall period is 7 days, and responses are reported using verbal and numeric rating scales. The item and scale scores are transformed to a 0 to 100 scale. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning and a high score for the global health status represents high health related quality of life (HRQoL), but a high score for a symptom scale/item represents a high level of symptomatology/problems.

The EORTC module QLQ-OH15 is a 15-item, well-accepted, and validated assessment tool focusing on oral problems and quality of life. The recall period for symptoms is 7 days and response options include 'not at all', "a little', 'quite a bit', and 'very much'. All of the items' measures range in score from 0 to 100. A high score for the symptom items represents a high level of symptomatology or problems.

PRO-CTCAE is a patient-reported item custom survey used to evaluate symptomatic treatment-emergent adverse events in participants on cancer clinical trials. The PRO-CTCAE custom survey consists of 18 items. Responses are provided on a 5-point Likert scale that ranges from 0 to 4. The recall period for symptoms is 7 days. Higher scores indicating greater severity/impact.

SXI is a validated questionnaire that explores how the participant experiences dry mouth (xerostomia) with 5 questions extracted from the original XI. Respondents are asked to choose 1 of 5 responses ("1-Never; 2-Hardly ever; 3-Occasionally; 4-Fairly often; and 5-Very often") to specific statements referring to the preceding 4 weeks. Each individual's responses are scored and summed to give a single XI score. Higher scores represent more severe symptoms.

The Epstein Taste Survey (ETS) consists of 17 items PRO instrument, specific to taste and smell changes. The ETS was developed for use in participants with head and neck cancer. This instrument will be used to measure treatment-related symptoms associated with talquetamab.

The STTA is a tool to assess the overall acuity of taste based on a 4-point scale, where 0 reflects no change and 4 represents almost complete loss of taste function. Higher score indicating severity.

Change from baseline in body weight will be reported.

Change from baseline in BMI will be reported.

Percentage of participants with dose reductions, dose interruptions, and dose discontinuations will be reported.

Smell identification testing will be performed using 4 booklets each containing 10 labels that will release a distinctive scent when scraped with a pencil. Participants will choose the appropriate scent from the associated options. The minimum possible score is a 0 and the maximum is a 40. A higher score indicates better smell/outcome.

Overall response rate is defined as the participants with a partial response (PR) or better according to the International Myeloma Working Group (IMWG) criteria.

CR or better response is defined as the participants who achieve a CR or better response according to the IMWG criteria.

VGPR or better response is defined as the percentage of participants who achieve a VGPR or better response according to the IMWG criteria.

Duration of response is defined as time from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria, or death due to any reason, whichever occurs first.

Time to response is defined as the time between date of first dose of talquetamab or ramantamig and the first efficacy evaluation at which the participant has met all criteria for PR or better.

PFS is defined as the time from the date of first dose of talquetamab or ramantamig to the date of first documented disease progression, as defined in the IMWG criteria, or death due to any cause, whichever occurs first.

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. Any AE occurring at or after the initial administration of study treatment through the day of last dose plus 30 days, or if beyond 30 days from last dose but is study treatment-related, is considered to be treatment-emergent.