LMY-920 for Treatment of Relapsed or Refractory Myeloma

Inclusion Criteria:

1. Subjects must have histologically confirmed myeloma relapsed or refractory after 3or more lines of therapy including an immunomodulatory agent, a proteasome inhibitorand an anti-CD38 antibody. Failing line of therapy is defined accordingly toInternational Myeloma Workshop Consensus Panel.

2. No evidence of CNS myeloma.

3. Male or female > 18 years of age.

4. ECOG Performance status ≤ 2.

5. Has measurable disease at the time of enrollment as defined by at least one of thefollowing:

• Serum M-protein greater or equal to 0.5g/dL

• Urine M-protein greater or equal to 200mg/24hr

• Serum free light chain (FLC) assay: involved light chain greater or equal to 10mg/dL provided serum FLC ratio is abnormal

• Bone marrow plasma cells greater than or equal to 30% total bone marrow cells

6. >2 weeks since prior radiation therapy or systemic therapy at the time ofleukapheresis.

7. Total bilirubin ≤ 1.5 mg/dL (except in patients with Gilbert's syndrome).

8. AST (SGOT)/ALT ≤ 2.5 X institutional upper limit of normal.

9. Serum creatinine < 2 mg/dL.

10. Cardiac ejection fraction of >45%, and no evidence of pericardial effusion, asdetermined by an echocardiogram.

11. Adequate pulmonary function as defined as pulse oximetry ≥ 92% on room air.

12. Subjects (or legal guardians) must have the ability to understand and thewillingness to sign a written informed consent document.

13. For women of childbearing potential: agreement to remain abstinent (refrain fromheterosexual intercourse) or use a contraceptive method with a failure rate of < 1%per year during the treatment period and for at least 90 days after the BAFF CAR-Tcell infusion.

14. For men: agreement to remain abstinent (refrain from heterosexual intercourse) oruse contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria:

1. ASCT within 6 weeks of informed consent.

2. History of allogeneic hematopoietic stem cell transplantation.

3. Active graft-versus-host disease.

4. Active central nervous system or meningeal involvement by myeloma. Subjects withuntreated brain metastases/CNS disease will be excluded from this clinical trialbecause of their poor prognosis and because they often develop progressiveneurologic dysfunction that would confound the evaluation of neurologic and otheradverse events. Patients with a history of CNS or meningeal involvement must be in adocumented remission by CSF evaluation and contrast-enhanced MRI imaging for atleast 90 days prior to registration.

5. Active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g.cervix, bladder, breast).

6. Less than 28 days elapsed between prior treatment with investigational agent(s) andthe day of lymphocyte collection.

7. New York Heart Association class IV congestive heart failure.

8. Cardiovascular disorders including unstable angina pectoris, clinically significantcardiac arrhythmias, myocardial infarction or stroke (including transient ischemicattack, or other ischemic event) within 6 months prior to registration.

9. Active infection requiring intravenous systemic treatment.

10. HIV seropositivity.

11. Pregnant or breastfeeding women are excluded from this study because LMY-920 therapymay be associated with the potential for teratogenic or abortifacient effects. Womenof childbearing potential must have a negative serum pregnancy test. Because thereis an unknown, but potential risk for adverse events in nursing infants secondary totreatment of the mother with LMY-920, breastfeeding should be discontinued. Thesepotential risks may also apply to other agents used in this study.

12. Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasiaon any bone marrow biopsy prior to initiation of therapy.

13. Serologic status reflecting active hepatitis B or C infection. Patients that arepositive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), orhepatitis C antibody must have a negative polymerase chain reaction (PCR) prior toenrollment. (PCR positive patients will be excluded.)

14. Patients with history of clinically relevant CNS pathology such as epilepsy, seizuredisorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe braininjuries, dementia and Parkinson's disease.

15. Subjects with uncontrolled intercurrent illness including, but not limited toongoing or active infection, symptomatic congestive heart failure, unstable anginapectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/socialsituations that would limit compliance with study requirements.

16. Known additional malignancies which require systemic treatment.

17. History of autoimmune disease (i.e. rheumatoid arthritis, systemic lupuserythematosus) with requirement of immunosuppressive medications (other than lowdose steroids) within 6 months.