A Phase 1 Study of Vaccination With Dendritic Cell (DC)/Multiple Myeloma (MM) Fusions in Combination With Elranatamab in Relapsed or Refractory Multiple Myeloma

Inclusion Criteria for Tumor Collection:

* Participants must have an established diagnosis of multiple myeloma
* Participant must have multiple myeloma and have relapsed following or are refractory to proteasome inhibitors, IMiDs and anti-CD38 mAb therapy
* Participants must have at least 3 prior lines of therapy
* Participants must be ≥18 years of age
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Participants must have \> 20% plasma cells in the bone marrow core or aspirate differential \<30 days prior to enrollment.
* ANC \> 1K/uL; Platelets \> 50 K/uL without transfusional support
* Participants must have adequate organ function as defined below:

  * Total bilirubin ≤1.5 x institutional upper limit of normal
  * AST ≤ 3 x institutional upper limit of normal
  * ALT ≤ 3 x institutional upper limit of normal
  * Creatinine clearance ≥ 40 mL/min for participants with creatinine levels above institutional normal
* The effects of DC/MM fusion vaccine on the developing human fetus are unknown. For this reason, women and men of child-bearing potential must agree to use adequate contraception (hormonal or barrier methods of birth control or abstinence) prior to study enrollment and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of treatment.
* Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria for Tumor Collection:

* Patients who are receiving any other investigational agents.
* Patients with purely non-secretory MM \[absence of a monoclonal protein (M protein) in serum as measured by electrophoresis and immunofixation and the absence of Bence- Jones protein in the urine defined by use of conventional electrophoresis and immunofixation techniques and the absence of involved serum free light chain \>100 mg/L\]. Patients with light chain MM detected in the serum by free light chain assay are eligible.
* Patients with Plasma Cell Leukemia
* Because of compromised cellular immunity, patients who have a known human immunodeficiency virus (HIV), active hepatitis C virus (HCV) or active hepatitis B virus (HBV).
* Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure (see Appendix H), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening will be documented by the investigator as not medically relevant.
* Active and clinically significant autoimmune or inflammatory disorder requiring active treatment
* Individuals with a history of a different malignancy are ineligible except for the following circumstances. Note: Individuals with a history of other malignancies are eligible if they have been disease-free for at least 2 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: non- invasive cancer (such as, any in situ cancers) and basal cell or squamous cell carcinoma of the skin.
* Female patients who are pregnant (positive β-HCG) or breastfeeding
* Prior organ transplant requiring immunosuppressive therapy.
* Patients who previously received PD-1 antibody and have experienced toxicities resulting in treatment discontinuation.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* History of GBS or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.

Eligibility Criteria Prior to Vaccination with DC/MM fusions

* Resolution of all elranatamab related ≥ grade 3 or higher toxicities to grade 1 or baseline. Isolated laboratory abnormalities that are not considered to be clinically significant are not exclusionary.
* Successful production of at least 2 vaccines with a minimum of 1 x 106 fusion cells per vaccine
* Absence of disease progression following 2 cycles of elranatamab therapy
* ECOG performance status ≤ 2

Participants must have adequate organ function as defined below:

* Total bilirubin ≤ 1.5 x institutional upper limit of normal
* AST ≤ 3 x institutional upper limit of normal
* ALT ≤ 3 x institutional upper limit of normal
* ANC \> 1K/uL; Platelets \> 50 K/uL without transfusional support
* Creatinine clearance ≥ 40 mL/min for participants with creatinine levels above institutional normal