Tumors deficient in DNA mismatch repair are known to display increased susceptibility to immune checkpoint inhibitors due to accumulation of DNA damage and increased neoantigen load. This suggests that deficiency in the BRCA-related DNA repair mechanism may also be a surrogate marker for immunotherapy response. The aim of this study was to examine the efficacy of the immune checkpoint inhibitor, nivolumab, in women with BRCA gene mutations and recurrent müllerian cancer. This retrospective case series followed six BRCA carriers who received nivolumab monotherapy (3.0 mg/kg, intravenous, day 1 and 15, every 4 weeks) as salvage therapy for recurrent epithelial ovarian (n = 5) and fallopian tubal (n = 1) cancers. Toxicity, treatment response, and survival were examined. Median age was 57 (range 51–64). BRCA1 and 2 mutations were equally distributed. All had high-grade serous histology, and all but one had advanced-stage disease at initial diagnosis. The majority had platinum-resistant disease (n = 4). All received salvage therapy prior to nivolumab therapy (median 3 lines), including PARP inhibitors (n = 3). The median number of nivolumab treatment cycles was 9, including 2 women receiving 18 cycles. Three women developed nivolumab-related toxicities, most commonly grade 2 hypothyroidism (n = 2). Median follow-up time was 13.4 months, and there were 3 complete responses, 1 partial response, and 2 patients with progressive disease. Objective response rate was 67% (4 out of 6). In conclusion, our study suggests that nivolumab monotherapy is well-tolerated and may be an effective salvage therapy for BRCA mutation carriers with recurrent epithelial ovarian, fallopian tubal, and primary peritoneal cancers.
Tumor necrosis factor (TNF) inhibitors are the mainstay of treatment for many inflammatory disorders. Although TNF inhibitors are generally well tolerated, roughly 30% of patients experience cutaneous side effects. Psoriasiform dermatitis occurs most frequently, but cutaneous reactions including eczema, xerosis, and palmoplantar pustulosis have also been reported. We report a case of a 56-year-old man with ulcerative colitis (UC) who presented with a five-day history of a tender bilateral axillary eruption. The patient's history was significant for erythema nodosum, which began two-months after initiating adalimumab for UC, and resolved upon holding this medication. One month after restarting adalimumab, the patient developed an eruption of the bilateral axilla, initially diagnosed as contact dermatitis and treated with hydrocortisone cream, which was ineffective. Five days later, the patient presented to the dermatology clinic. Physical examination revealed large, tender erosions surrounded by erythema in the bilateral axilla. Histopathology showed an interface dermatitis with focal full thickness epidermal necrosis. Clinicopathologic correlation confirmed a bullous drug eruption. The patient was treated with a one-week course of clobetasol ointment, and adalimumab was promptly discontinued. One month later, the eruption had essentially resolved. To our knowledge, this is the first report of a localized bullous drug eruption with histologic features of full-thickness epidermal necrosis occurring in association with anti-TNF therapy. Although rare, existing reports of toxic epidermal necrolysis due to anti-TNF therapy raise concern for the potential progression of this patient's eruption with anti-TNF continuation. This case highlights the possibility of a localized drug eruption with full-thickness epidermal necrosis due to anti-TNF therapy, and underscores the need to maintain a high index of suspicion regarding such a reaction.
Tumors deficient in DNA mismatch repair are known to display increased susceptibility to immune checkpoint inhibitors due to accumulation of DNA damage and increased neoantigen load. This suggests that deficiency in the BRCA-related DNA repair mechanism may also be a surrogate marker for immunotherapy response. The aim of this study was to examine the efficacy of the immune checkpoint inhibitor, nivolumab, in women with BRCA gene mutations and recurrent müllerian cancer. This retrospective case series followed six BRCA carriers who received nivolumab monotherapy (3.0 mg/kg, intravenous, day 1 and 15, every 4 weeks) as salvage therapy for recurrent epithelial ovarian (n = 5) and fallopian tubal (n = 1) cancers. Toxicity, treatment response, and survival were examined. Median age was 57 (range 51-64). BRCA1 and 2 mutations were equally distributed. All had high-grade serous histology, and all but one had advanced-stage disease at initial diagnosis. The majority had platinum-resistant disease (n = 4). All received salvage therapy prior to nivolumab therapy (median 3 lines), including PARP inhibitors (n = 3). The median number of nivolumab treatment cycles was 9, including 2 women receiving 18 cycles. Three women developed nivolumab-related toxicities, most commonly grade 2 hypothyroidism (n = 2). Median follow-up time was 13.4 months, and there were 3 complete responses, 1 partial response, and 2 patients with progressive disease. Objective response rate was 67% (4 out of 6). In conclusion, our study suggests that nivolumab monotherapy is well-tolerated and may be an effective salvage therapy for BRCA mutation carriers with recurrent epithelial ovarian, fallopian tubal, and primary peritoneal cancers.
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