EP241 - Dermatomyositis Remission Following Dostarlimab Therapy for Mismatch Repair Deficient Rectal Cancer: A Case Report

Purpose/Background: We present the first case report of paraneoplastic dermatomyositis (DM) presenting in MMR deficient (dMMR) rectal cancer that resolved with dostarlimab treatment in conjunction with steroids and intravenous Immunoglobulin (IVIG). MMR deficiency rarely occurs in rectal cancer, representing an estimated 2-5% of cases (Lunenberg et al., 2025). Paraneoplastic DM itself is rare, occurring in fewer than 1% of gastrointestinal malignancies (Bowerman et al., 2020; Hill et al.,). The rate in rectal cancer is unknown, but there are reports of DM resolving with treatment of rectal cancer treatment (Fujii et al., 2000; Sawamura et al., 2025). These cases involved surgical resection and either neoadjuvant or adjuvant treatment with chemotherapy or chemoradiation. Dostarlimab, an anti-PD-1 antibody, approved for dMMR solid tumors has demonstrated high rates of complete clinical response in dMMR rectal cancer, but its safety and efficacy in paraneoplastic syndromes is unknown.

Methods/Interventions: This is a 60-year-old Caucasian male who was initially diagnosed with DM after he presented with progressive muscle weakness, dysphagia, a heliotrope rash, Gottron's papules, creatine kinase (3,045 U/L) and a skin biopsy pathology supportive of a connective tissue disorder. His dysphagia became severe enough to require gastrostomy tube placement.

He underwent colonoscopy and EGD which demonstrated a non-obstructed, ulcerated/fungating mass of the middle and upper rectum (Table 1), with biopsy consistent with moderately differentiated adenocarcinoma, MLH1 and PMS2 deficient. MLH1 methylation testing was positive. Rectal MRI and Chest/Abdominal CT staged his cancer as cT3N0.

Results/Outcomes: The patient was offered a total neoadjuvant therapy approach with the option for resection but deferred due to the anticipated morbidity. As an alternative, he began dostarlimab 500 mg one month after diagnosis, and he has completed 7/9 cycles. His DM was treated with IV methylprednisolone, transitioned to PO prednisone, and tapered slowly over a 4-month period. One month after initial diagnosis, he underwent IVIG infusion daily for a 3-day course, followed by 2g/kg over 2 days monthly starting the month after diagnosis.

At last visit, he had significant improvement in his muscle weakness, with restoration of ambulatory function and tolerance of soft diet. He is off steroids. Flexible sigmoidoscopy 4 months after initiating treatment showed an improved but persistent tumor (Table 1). His creatine kinase has normalized. The patient has not experienced any immune-mediated adverse events (irAEs).

Conclusion/Discussion: This is the first reported case of paraneoplastic dermatomyositis resolving with dostarlimab treatment of dMMR rectal cancer. Dostarlimab is an evolving new treatment option whose efficacy is being actively investigated (Cercek et al., 2025). Choosing to give immunotherapy to this patient with dermatomyositis, an autoimmune disorder, was debated given autoimmune conditions are considered contraindications for use of immune checkpoint inhibitors (André et al., 2023; Le et al., 2020; Lenz et al., 2022; Marabelle et al., 2020). Nevertheless, we present a case where immunotherapy effectively controlled the symptoms of an autoimmune paraneoplastic syndrome. Oncologic outcomes are pending but appear promising.

Table 1
Endoscopic appearance of tumor at diagnosis (left) and after 4 months of treatment (right).