Inclusion Criteria:

• Ability to understand and the willingness to sign a written informed consent document.
• Age ≥18 years at the time of signing informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Life expectancy of greater than 12 weeks

• Histologically or cytologically confirmed diagnosis of relapsed/refractory multiple myeloma. Documented measurable disease includes at least one or more of the following criteria:

  • Serum M-protein ≥1.0 g/dL
  • Urine M-protein ≥200 mg/24 hours
  • Involved serum free light chain ≥100 mg/L with abnormal κ/λ ratio
  • Bone marrow plasma cells ≥30%
• Relapsed/refractory multiple myeloma with at least 3 prior regimens of systemic therapy including proteasome inhibitor, IMiDs and anti-CD38 antibody; or has "triple-refractory" disease following treatment with proteasome inhibitor, IMiD and anti-CD38 antibody, as part of the same or different regimens.

Note: IMWG criteria defines refractory disease as disease progression on or within 60 days of receiving a therapy Note: Induction treatment with or without hematopoietic stem cell transplant and with or without maintenance is considered a single regimen.

• Adequate organ and marrow function as defined below:

  • O2 saturation ≥92% on room air while awake
  • LVEF ≥40% by ECHO or MUGA scan
  • ANC ≥1.0k/μl, PLT ≥50k/μl, (NOTE: Platelet transfusion not allowed within 7 days; growth factor neupogen not allowed within 7 days, neulasta within 14 days)
  • Creatinine clearance ≥30 mL/min and not on dialysis
  • AST/ALT <3 x ULN
  • Direct bilirubin <1.5 x ULN (allow x 3 ULN for Gilbert's syndrome)
  • PTT, PT/INR <1.5 x ULN, unless on a stable dose of anti-coagulant for a thromboembolic event (Patients with any history of thromboembolic stroke; or history or Grade 2 or greater hemorrhage within 60 days are excluded)
• Resolution of AEs from any prior therapy to ≤ Grade 1 (≤ G2 alopecia and ≤ G2 sensory neuropathy are allowed, cytopenias allowed per eligibility criteria above)
• Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• The effects of TriPRIL CAR T cells on the developing human fetus are unknown. Male and female participants of childbearing potential must agree to use highly effective methods of birth control prior to study entry, for the duration of study participation, and through 6 months after completion of TriPRIL CAR T cells administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

NOTE: Highly effective contraception methods include:

• Total abstinence
• Female sterilization (tubal ligation, bilateral oophorectomy, and/or hysterectomy)
• Male sterilization, at least 6 months prior to screening
• Intrauterine device

• Oral, injected, or implanted hormonal contraception AND barrier methods of contraception

  • Willing to comply with and able to tolerate study procedures, including Long-term Safety Follow-up lasting up to 15 years per FDA guidance

Exclusion Criteria:

• Treatment with any of the following therapies as specified below:

  • Any prior systemic treatment for multiple myeloma within the 14 days prior to scheduled leukapheresis unless discussed with the medical monitor
  • Receiving high-dose (e.g., >10 mg prednisone or equivalent) systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to leukapheresis
  • Autologous stem cell transplantation within 3 months prior to leukapheresis
  • Any prior allogeneic stem cell transplantation
  • Other CAR-T cell therapy within 6 months of leukapheresis
• Plasma cell leukemia or history of plasma cell leukemia
• Patients with extramedullary disease only without meeting criteria for measurable disease as per inclusion criteria above.
• No Bispecific T cell engagers withing 6 months of apheresis
• No bendamustine within 6 months of apheresis
• Patients with solitary plasmacytomas without evidence of other measurable disease
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to CAR- T cells
• Contraindication to the protocol-specified doses of fludarabine or cyclophosphamide
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) with the exception of ≤ G2 alopecia and grade ≤2 sensory neuropathy.
• Active bacterial, viral, or fungal infection requiring systemic treatment (isolated fever may not constitute active infection in and of itself, e.g., related to disease)
• Symptomatic congestive heart failure
• Unstable angina, arrhythmia, or myocardial infarction (MI) within 6 months prior to screening
• Significant pulmonary dysfunction
• Auto-immune disease requiring immunosuppressive therapy
• Pulmonary embolism or DVT within three months of enrollment or uncontrolled thromboembolic events. Therapeutic dosing of anticoagulants (e.g., warfarin, low molecular weight heparin, Factor Xa inhibitors) is allowed for history of DVT or PE if greater than three months from time of enrollment. Prophylactic anticoagulation is allowed.
• Recent severe hemorrhage (within the past 60 days)

• Seropositive for and with evidence of active hepatitis B or C infection at time of screening, or HIV seropositive

  • Subjects with a history of hepatitis B but have received antiviral therapy and have non-detectable viral DNA for 6 months are eligible
  • Subjects seropositive because of hepatitis B virus vaccine with no signs or active infection are eligible
  • Subjects who had hepatitis C but have received antiviral therapy and show no detectable HCV viral RNA for 6 months are eligible
• Active central nervous system (CNS) involvement by malignancy. NOTE: subjects who are asymptomatic, stable, and received prior effective treatment for CNS disease may be eligible after discussion with the medical monitor.
• Any sign of active or prior CNS pathology including history of epilepsy, seizure, paresis, aphasia, stroke, subarachnoid hemorrhage or CNS bleed, severe brain injury, dementia, cerebellar disease, Parkinson's disease, organic brain syndrome or psychosis.
• Active malignancy not related to myeloma that has required therapy in the last 3 years or is not in complete remission. Exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or prostate cancer that does not require therapy. Other similar malignant conditions may be discussed with and permitted by the medical monitor.
• Females who are pregnant or breastfeeding or females of childbearing potential not using an effective method of birth control
• Subjects with any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in study (or full access to medical records) as written including follow up, the interpretation of data or place the subject at unacceptable risk
• Participants taking any other medicine concurrently that may interfere with the study (need to consult with the principle investigator)