Treatment may be held for up to 14 days for unrelated adverse events, or as clinically indicated, at the discretion of the treating physician. DF/HCC Protocol #: 18-280 Protocol Version Date: 10.17.2020 21 6.2 Management of Nivolumab-Related Infusion Reactions Infusion reactions to Nivolumab may consist of fever, chills, rigors, headache, rash, urticaria, angioedema, pruritus, arthralgias, hypo- or hypertension, bronchospasm, or other symptoms. Infusion reactions should be graded according to NCI CTCAE version 4.0 guidelines. For Grade 1 symptoms: (Mild reaction; infusion interruption not indicated; intervention not indicated) Infusion rate may be slowed or interrupted and restarted at 50% of the original infusion rate when symptoms resolve; if no further complications ensue after 30 minutes, the rate may be increased to 100% of the original infusion rate. Monitor patient closely. The following prophylactic pre-medications are recommended for future infusions: diphenhydramine 50 mg (or equivalent) and/or paracetamol 325 to 1000 mg (acetaminophen) at least 30 minutes before additional nivolumab administrations, slowing infusion rate as above. For Grade 2 symptoms : (Moderate reaction requires therapy or infusion interruption but responds promptly to symptomatic treatment [ e.g., antihistamines, non-steroidal anti- inflammatory drugs, narcotics, corticosteroids, bronchodilators, IV fluids]; close observation for recurrence and treatment medications may need to be continued for 24-48 hours), and no further nivolumab will be administered at that visit. Stop the nivolumab infusion, begin an IV infusion of normal saline, and treat the subject with diphenhydramine 50 mg IV (or equivalent) and/or paracetamol 325 to 1000 mg (acetaminophen); remain at bedside and monitor patient until resolution of symptoms. Corticosteroid or bronchodilator therapy may also be administered as appropriate. If the infusion is interrupted, then restart the infusion at 50% of the original infusion rate when symptoms resolve; if no further complications ensue after 30 minutes, the rate may be increased to 100% of the original infusion rate. Monitor patient closely. If symptoms recur, re administer diphenhydramine 50 mg IV, and remain at bedside and monitor the patient until resolution of symptoms. The following prophylactic premedications are recommended for future infusions: diphenhydramine 50 mg (or equivalent) and (acetaminophen) (or paracetamol) 325 to 1000 mg should be administered at least 30 minutes before additional nivolumab administrations. If necessary, corticosteroids (recommended dose: up to 25 mg of IV hydrocortisone or equivalent) may be used. For Grade 3 or Grade 4 symptoms: (Severe reaction): Grade 3 symptoms : prolonged [ i.e., not rapidly responsive to symptomatic medication and/or brief interruption of infusion]; recurrence of symptoms following initial improvement; hospitalization indicated for other clinical sequelae [ e.g., renal impairment, pulmonary infiltrates]). Grade 4 symptoms: (life threatening; pressor or ventilatory support indicated). Nivolumab will be permanently discontinued:  Immediately discontinue infusion of nivolumab. Begin an IV infusion of normal saline, and bronchodilators, epinephrine 0.2 to 1 mg of a 1: 1,000 solution for subcutaneous administration or 0.1 to 0.25 mg of a 1: 10,000 solution injected slowly for IV administration, and/or diphenhydramine 50 mg IV with methylprednisolone 100 mg IV (or equivalent), as needed. Patient should be monitored until the investigator is comfortable that the symptoms will not recur.  In the event of anaphylaxis, follow institutional guidelines.  In the case of late-occurring hypersensitivity symptoms ( e.g., appearance of a localized or generalized pruritus within 1 week after treatment), symptomatic treatment may be given ( e.g., oral antihistamine, or corticosteroids). Additional treatment prior to next dose as per guidelines above.  Please note that late occurring events including isolated fever and fatigue may represent the presentation of systemic inflammation. Please evaluate accordingly. 6.3 Management of Other Nivolumab-Related AEs DF/HCC Protocol #: 18-280 Protocol Version Date: 10.17.2020 22 Please refer to Appendix B: Dose Modifications for Nivolumab-related AEs. 6.4 Management of DC/MM Vaccine Site Reaction If a patient experiences a grade 2 or higher (graded according to CTCAE v4.0) injection site reaction during the days when GM-SCF is administered, subsequent doses of GM-CSF may be held until the injection site reaction improves to grade 1 or less at the discretion of the treating investigator. On the day of subsequent vaccine administrations, patients will receive pre-medication with diphenhydramine (Benadryl) 25-50 mg and/or acetaminophen (Tylenol) 650-1000 mg to minimize potential allergic-related symptoms. 7. IDENTIFICATION OF TREATMENT LIMITING TOXICITIES Treatment limiting toxicities (TLT) will be defined as toxicity judged to be possibly or definitely related to the study treatment and meeting the following criteria:  Grade 3 or higher non-hematologic toxicities that do not resolve within 14 days of onset; o Please note the following exceptions that necessitate immediate discontinuation of therapy:  Grade 4 creatinine elevation  Grade 3 or higher pulmonary toxicity  Grade 3 or higher ALT, AST or total bilirubin elevation  Grade 3 or higher adrenal insufficiency  Grade 3 or higher neurological adverse event  Grade 3 or higher myocarditis  Grade 4 or higher clinically significant non-hematologic toxicities;  Grade 4 or higher hematologic toxicities that do not resolve to grade 1 or baseline within 7 days of onset; o Please note that this excludes lymphopenia, as mentioned in section 5.9.3;  Grade 4 or higher nivolumab infusion reactions. Patients experiencing TLT will not receive further therapy If 3 or more patients experience a TLT within the first 28 days of initiating therapy among the first 10 patients enrolled, then accrual will be suspended. TLTs will be defined per the above criteria with grades determined by CTCAE version 4.0 that are possibly, probably or definitely related to the study treatment. Patients will be monitored for the occurrence of TLTs during the first 28 days of treatment. Once the 10th participant is enrolled, accrual will be paused until the 10th participant completes a full cycle of treatment (28 days) without experiencing any TLTs. 8. ADVERSE EVENTS: LIST AND REPORTING REQUIREMENTS Adverse event (AE) monitoring and reporting is a routine part of every clinical trial. The following list of reported and/or potential AEs (Section 7.1) and the characteristics of an observed AE (Section 7.2) will determine whether the event requires expedited reporting in addition to routine reporting. 8.1 Expected Toxicities 8.1.1 Adverse Events Lists 8.1.1.1 Adverse Event List(s) for Nivolumab Events that are listed as very common (experienced in ≥10% of patients) according to the current IB (Version 16 dated June 23, 2017) include the following: fatigue and diarrhea Events that are listed as common (experienced in ≥1% to <10% of patients) include: hypothyroidism, hyperthyroidism, hyperglycemia, nausea, vomiting, chills, colitis, stomatitis, asthenia, gastritis, DF/HCC Protocol #: 18-280 Protocol Version Date: 10.17.2020 23 abdominal pain, constipation, dry mouth, pyrexia, edema peripheral, infusion related reactions, increased lipase, increased amylase, increased aspartate aminotransferase, increase alanine aminotransferase, increased creatinine, increased thyroid stimulating hormone, hyponatremia, decreased appetite, back pain, myalgia, arthralgias, pain in extremity, headache, pruritis, dizziness, pneumonitis, dyspnea, cough, rash, vitiligo, dry skin, erythema, maculopapular rash Events that are listed as uncommon ≥0.001% of patients to < 1% include the following: musculoskeletal pain, arthritis, neck pain, musculoskeletal chest pain, bone pain, polyarthritis, peripheral neuropathy, peripheral sensory neuropathy, peripheral motor neuropathy, vasculitis, lung infiltration, tubulointerstitial nephritis, renal failure, acute kidney injury, hypertension, hypotension, alopecia, dermatitis acneiform, macular rash, urticaria, dermatitis, erythematous rash, generalized rash, papular rash, psoriasis, pustular rash, drug eruption, bronchitis, hypersensitivity, upper respiratory infections, edema, facial edema, peripheral swelling, localized edema, nephritis, autoimmune hepatitis, hepatitis, pancreatitis, uveitis, diabetes mellitus, thyroiditis, autoimmune hypophysitis, increased blood bilirubin, hypopituitarism, adrenal insufficiency, tachycardia, autoimmune colitis, atrial fibrillation, vertigo, dry eye, vision blurred, mucosal inflammation, generalized edema, respiratory failure, lung infiltration Events that are listed as rare risk (experienced by ≥0.00001% to <0.001% of patients) include arrhythmias, Stevens Johnson Syndrome, dermatitis exfoliative, allergic dermatitis, rosacea, erythema multiforme, diabetic ketoacidosis, autoimmune hypothyroidism, iridocyclitis, periorbital edema, mouth ulceration, acute pancreatitis, acute hepatitis, sarcoidosis, anaphylactic reaction, myositis, musculoskeletal discomfort, osteoarthritis, pain in jaw, polymyalgia rheumatica, polymyositis, rhabdomyolysis, polyneuropathy, burning sensation, encephalitis, Guillain-Barre syndrome, myasthenia gravis, demyelination, autoimmune nephritis, organizing pneumonia, acute respiratory distress syndrome, vasculitis Events that are listed as very rare (experienced by < 0.0001%) include ventricular arrhythmias, mucosal ulceration, demyelinating polyneuropathy, myasthenic syndrome, and toxic epidermal necrolysis 8.1.1.2 Adverse Event List(s) for DC/MM Fusion Vaccines Toxicities related to the vaccine are:  Hematologic: Leukopenia  Neurologic: Headache  Gastrointestinal: Diarrhea, decrease appetite.  Constitutional: Weakness chills and fever.