Nivolumab for Relapsed, Refractory, or Detectable Disease Post Chimeric Antigen Receptor T-cell Treatment in Patients With Hematologic Malignancies

This phase II trial studies how well nivolumab works for the treatment of hematological malignancies that have come back (relapsed), does not respond (refractory), or is detectable after CAR T cell therapy. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then for up to 5 years.

Eligibility Criteria:
Inclusion Criteria:

* Diagnosis of the following tumor types

  * Non Hodgkin-lymphoma, including:

    * Diffuse large B-cell lymphoma: Histopathologic confirmation
    * Mantle cell lymphoma: Histopathologic confirmation
    * Follicular lymphoma, all grades: Histopathologic confirmation
    * Marginal zone lymphoma: Histopathologic confirmation
  * Chronic lymphocytic leukemia: Histopathologic or flow cytometric confirmation
  * Multiple myeloma: Histopathologic or flow confirmation
* Relapsed, refractory, or detectable disease after treatment with chimeric antigen receptor T-cells

  \* Multiple Myeloma: patients must have exhausted all treatment options known to provide clinical benefit, and are refractory to a minimum of 3 prior lines of therapy (including an immunomodulatory imide drug \[IMiD\], proteasome inhibitor \[PI\], or anti-CD38 monoclonal antibody)
* Have measurable disease, defined by histology:

  * Non-Hodgkin's lymphoma, based on presence of lesions \>= 1.5 cm that can be accurately measured in 2 dimensions by computed tomography (CT) (preferred) or magnetic resonance imaging (MRI), and are not included in any prior field of radiation therapy
  * Chronic lymphocytic leukemia: circulating lymphocytes \>= 5,000 / mm\^3
  * Multiple myeloma, based on the International Myeloma Working Group (IMWG) criteria of having one or more of the following findings:

    * Serum M protein \>= 1.0 g/dL
    * Urine M protein \>= 200 mg/24 hours
    * Involved serum free light chain level \>= 10 mg/dL with abnormal kappa/lambda ratio
    * Measurable biopsy-proven plasmacytomas (\>= 1 lesion has a single diameter \>= 2 cm)
    * Bone marrow plasma cells \>= 30%
* Age 18 years and older, and have the capacity to give informed consent
* Anticipated survival of \> 3 months
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Post CAR T cell receipt of intervening palliative radiation therapy is allowed
* Estimated glomerular filtration rate (eGFR) \>= 20 ml/min
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x upper limit of normal (ULN)
* Total bilirubin =\< 2 x ULN
* Absolute neutrophil count (ANC) \>= 1,000/uL
* Platelets \>= 50,000/uL
* Hemoglobin \>= 8 g/dL

Exclusion Criteria:

* Receipt of intervening therapy after CAR T-cell infusion
* History of another primary malignancy that has not been in remission for at least 1 year (with the exception of non-melanoma skin cancer, curatively treated localized prostate cancer, curatively treated superficial bladder cancer and cervical carcinoma in site on biopsy or a squamous intraepithelial lesion on papanicolaou \[PAP\] smear)
* Active hepatitis B, hepatitis C at time of screening
* Known (human immunodeficiency virus \[HIV\]) seropositivity
* Subjects with uncontrolled infection
* Concurrent use of other anticancer agents or experimental treatments
* Active autoimmune disease requiring immunosuppressive therapy with the exception of vitiligo and autoimmune alopecia
* Known active central nervous system (CNS) involvement
* Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses are permitted in absence of active autoimmune disease
* Known history of any active infectious pneumonitis
* Presence of acute or chronic graft-versus-host disease (GVHD) requiring active treatment unless limited to skin involvement and managed with topical steroid therapy alone
* Has active cytokine release syndrome
* Pregnancy or breastfeeding: Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (urine pregnancy test: minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[hCG\]) within 14 days of the first dose of study drug. Women must not be breastfeeding. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy. Females of childbearing potential and males who have partners of childbearing potential must agree to use 2 effective contraceptive methods during the study and for 8 months following the last dose of nivolumab