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Immunotherapy has become a mainstay therapeutic in a variety of malignancies. Checkpoint inhibitors are used to enhance the endogenous immune response to target malignancy. The primary targets of checkpoint inhibitors include programed cell death receptor 1 (PD-1), programed cell death ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). Despite clinical benefits, immune checkpoint inhibitors are associated with side effects termed immune-related adverse events (irAEs). We report a case of the PD-1 inhibitor (pembrolizumab) causing severe distal renal tubular acidosis (RTA). The patient presented with altered mental status and was found to have a severe non-anion gap metabolic acidosis after other potential etiologies were ruled out. We review the etiology of immune checkpoint inhibitor-induced RTA and review the case reports that have been described in the literature.

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Patient: Male, 56Final Diagnosis: Advanced stage squamous cell carcinoma of the head and neckSymptoms: Rapidly enlarging mass in left neckMedication: —Clinical Procedure: —Specialty: OncologyObjective:Unusual clinical courseBackground:Cancer is the second leading cause of death internationally, resulting in millions of deaths each year. While treatment in the past has heavily relied on surgery and radiotherapy, chemotherapy and immunotherapy are being increasingly utilized depending on disease presentation.Case Report:A 56-year-old male presented to the Emergency Department with a 3-week history of a rapidly enlarging left supraclavicular neck mass. Computed tomography scan revealed a 12×13 cm mass extending from the angle of the mandible to the supraclavicular area. A biopsy confirmed advanced stage squamous cell carcinoma of the head and neck. The patient was started on a chemotherapy regimen of docetaxel, cisplatin, and 5-fluorouracil (TCF). The tumor progressed through chemotherapy, which was switched to cetuximab; however, this therapy was discontinued after an anaphylactic reaction. Palliative radiation treatment was begun along with pembrolizumab. Pembrolizumab was continued, and after 9 cycles, the patient’s cancer was almost in complete remission. Three months later, disease progression was once again noted with pembrolizumab treatment, which was subsequently discontinued. The patient was started on paclitaxel and carboplatin chemotherapy regimen as a last resort, despite failure of prior TCF treatment, and the patient responded, this time with complete remission in 4 months.Conclusions:This case demonstrates a unique outcome in which a patient who previously was resistant to chemotherapy, later responded to chemotherapy after a trial of radiation therapy and immunotherapy. Immunotherapy may have a synergistic effect with radiation therapy and play a role in tumor sensitivity to chemotherapy in head and neck cancer treatment.

4570 Background: Mismatch repair deficiency (dMMR) and microsatellite instability-high (MSI-H) occur in a small subset of urothelial carcinoma (UC) and confer a sensitivity to immunotherapy in multiple solid tumors. Due to the rarity of this patient subset in UC, there is a lack of prospective data on their prevalence or of clinical outcomes with immunotherapy and other treatment modalities. Methods: We performed a systematic review with the objectives of estimating the prevalence of dMMR and MSI-H in urothelial bladder cancer (BC) and upper tract urothelial carcinoma (UTUC) apart from estimating survival and clinical outcomes of treatment. We searched for published prospective and retrospective studies, review articles, case reports, case series, conference proceedings, letters, commentaries, and editorials on dMMR and MSI-H in BC and UTUC published up to 10/26/2022 in PubMed, Cochrane CENTRAL, Embase and Web of Science: Core Collection databases. The study protocol is registered on the PROSPERO database (CRD42022365690). Prevalence data were analyzed using meta-analysis with random-effects models and are reported here. Results: A total of 1,750 studies were screened, of which 125 were included. Thirty-six studies (including 5,113 patients) reported frequencies of dMMR, and 42 studies (including 21,291 patients) reported on MSI-H. Of the total included patients, sex was reported in 11,225, with 72.6% being male and 27.4% female. Age ranged from 17-97 years. Reported primary site was BC in 64.4%, UTUC in 16.3% and not stated in 19.3%. Disease stage reported in 5,341 patients was M0 in 75.0% and M1 in 25.0%. Of the M0 patients, tumor stage data were available in 3,149 patients: Ta-T1 in 33.6% and T2-T4 in 66.4%. The pooled weighted prevalence of dMMR in UC patients was 6% (95% CI 5-8%). The breakdown for BC and UTUC were 2% (95% CI 1-3%) and 9% (95% CI 7-12%), respectively. The three most frequent MMR protein loss patterns in UC, BC and UTUC are shown in the table. Out of 42 studies reporting MSI status, 21 used polymerase chain reaction (PCR) and 21 used next-generation sequencing (NGS). Pooled weighted prevalence of MSI-H in UC was 3% (95% CI 2-3%). In BC, the prevalence was 1% (95% CI 1-1%) and in UTUC, it was 11% (95% CI 8-13%). Conclusions: dMMR and MSI-H were observed more frequently in UTUC than BC. Further analysis on survival and clinical outcomes of dMMR/MSI-H UC with different treatment modalities is ongoing. Additionally, clinical trials in dMMR and/or MSI-H UC are in development to study immunotherapeutic strategies to improve outcomes in both early and advanced stages for this small but important subset of patients. [Table: see text]