Dendritic Cell Therapy, Cryosurgery, and Pembrolizumab in Treating Patients With Non-Hodgkin Lymphoma

Inclusion Criteria:

Age >= 18 years
Histological confirmation of biopsy-proven non-Hodgkin lymphoma, excluding chronic lymphocytic leukemia, primary central nervous system (CNS) lymphoma and Burkitt's lymphoma; Note: small lymphocytic lymphoma (SLL) is allowed
Patients with indolent non-Hodgkin lymphoma (NHL) must have had >= 1 regimen of rituximab-containing regimen; Note: this includes follicular lymphoma (FL), marginal lymphoma and mucosa-associated lymphoid tissue (MALT)
Patients with aggressive NHL must have had >= 2 regimens; Note: This includes diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), primary mediastinal large B-cell lymphoma (PMBCL), and T cell lymphoma

Patient with aggressive NHL must have received prior therapy - at a minimum:

Anti-CD20 monoclonal antibody unless tumor is CD20 negative and
An anthracycline containing regimen
Transformed FL must have had therapy for FL and be refractory to chemotherapy for DLBCL

Chemotherapy refractory disease in aggressive NHL is defined as

Stable disease of =< 12 months or progressive disease as best response to most recent chemotherapy containing regimen
Disease progression or recurrence =< 12 months of prior autologous stem cell transplantation (SCT)
Patients with aggressive NHL must have failed autologous hematopoietic stem cell transplantation (HSCT), or are ineligible or not consenting to autologous HSCT
Patient must have at least 3 measurable lesions that are >= 1.5 cm in one dimension; one of the lesions must be >= 2.0 cm and is amenable to image-guided cryoablation and multiple vaccine injections as determined by interventional radiology and principal investigator (PI) (including tumors that can be safely accessed using imaging guidance and treated with minimal risk to adjacent structures)
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to registration)
Absolute lymphocyte count >= 200/mm^3 (obtained =< 14 days prior to registration)
Platelet count >= 50,000/mm^3 (obtained =< 14 days prior to registration)
Hemoglobin >= 8.0 g/dL (obtained =< 14 days prior to registration)
Total bilirubin =< 1.5 x upper limit of normal (ULN), unless due to Gilbert's disease (obtained =< 14 days prior to registration)
Aspartate transaminase (AST/serum glutamic-oxaloacetic transaminase [SGOT]) and alanine transaminase (ALT/serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (obtained =< 14 days prior to registration)
Creatinine =< 1.5 x ULN or calculated creatinine clearance >= 60 mL/min for subject with creatinine ˃ 1.5 x institutional ULN (obtained =< 14 days prior to registration)
Negative serum pregnancy test for women of childbearing potential =< 7 days prior to registration; Note: a second pregnancy test may be required =< 72 hours prior to receiving the first dose of study medication
Negative human immunodeficiency virus (HIV), hepatitis B and C, and tuberculosis (TB) test
Provide written informed consent
Willing to return to the enrolling institution for follow-up (during active treatment and active monitoring phase of the study)
Ability to complete questionnaire(s) by themselves or with assistance
Willing to provide tissue and blood samples for research purposes
Willing to use adequate contraception while on the study and until 120 days after the last dose of study drug

Exclusion Criteria:

Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:

Pregnant women
Nursing women
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
Serious non-malignant disease such as active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations or other conditions which in the opinion of the investigator would compromise protocol objectives
Currently receiving or have received any other investigational agent considered as a treatment for the primary neoplasm =< 28 days or within 4 half-lives (whichever is shorter) of the agent prior to registration

History of other primary malignancy requiring systemic treatment within 6 months of protocol enrollment; patients must not be receiving chemotherapy or immunotherapy for another cancer; patients must not have another active malignancy requiring active treatment with the following acceptable EXCEPTIONS:

Basal cell carcinoma, squamous cell carcinoma, or melanoma of the skin that has undergone or will undergo potentially curative therapy
In situ cervical cancer that has undergone or will undergo potentially curative therapy
Prior allogeneic bone marrow or peripheral blood stem cell transplantation
Prior autologous bone marrow or peripheral blood stem cell transplantation =< 100 days prior to registration or if recovery from the transplant is inadequate
Major surgery other than diagnostic surgery =< 4 weeks prior to registration
Prior chemotherapy or radiation therapy =< 2 weeks prior to registration or who has not recovered (i.e. to =< grade 1 or baseline) from an adverse event due to the previously administered therapy
History of hypersensitivity and anaphylactoid reactions to pneumococcal vaccine or any component of the formulation, including diphtheria toxoid

Active autoimmune disease such as Crohn's disease, rheumatoid arthritis, Sjogren's disease, systemic lupus erythematosus, or similar conditions requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease/syndrome difficult to control in the past

EXCEPTIONS:

Vitiligo or resolved childhood asthma/atopy
Intermittent use of bronchodilators or local steroid injections
Hypothyroidism stable on hormone replacement,
Diabetes stable with current management
History of positive Coombs test but no evidence of hemolysis
Psoriasis not requiring systemic treatment
Conditions not expected to recur in the absence of an external trigger
Coagulopathy, including the use of Coumadin or heparin anticoagulants that cannot be discontinued for the cryoablation procedure; NOTE: heparin for line patency without detectable lab abnormalities for coagulation will be allowed
Corticosteroid use =< 2 weeks prior to registration; NOTE: patients must be off corticosteroids for at least 2 weeks prior to registration; this includes oral, IV, subcutaneous, or inhaled route of administration; patients on chronic corticosteroid for adrenal insufficiency or other reasons may enroll if they receive less than 10 mg/day of prednisone (or equivalent)
Active CNS malignancy
Evidence of interstitial lung disease or active, non-infectious pneumonitis
Received a live vaccine =< 30 days prior to registration
New York Heart Association classification III or IV cardiovascular disease or recent myocardial infarction or unstable angina pectoris or cardiac arrhythmia =< 30 days prior to registration