Pembrolizumab-induced nephrotoxicity in a patient with breast cancer.

The introduction of immunotherapy has revolutionized the treatment and improved outcomes of multiple types of cancer. Although breast cancer is a less immune-responsive tumor type, the incorporation of pembrolizumab into chemotherapy regimens in the neoadjuvant and first-line metastatic setting for the triple-negative disease has improved outcomes. However, the use of this type of treatment is associated with a spectrum of adverse events. Although rarely affected, kidneys can be a target for immunotherapy, leading to irreversible injury if not recognized and addressed early. A 52-year-old woman presented with clinical stage II right breast cancer diagnosed at an outside facility. Neoadjuvant docetaxel/carboplatin/pembrolizumab every 3 weeks was started. Given the partial response on MRI after the 4th cycle, treatment was switched to doxorubicin/cyclophosphamide. However, pembrolizumab was held in cycle 2 due to the rash and then resumed in cycle 3 after the resolution of symptoms. Elevated creatinine was noted 3 weeks after the last dose of pembrolizumab without improvement despite adequate fluid resuscitation. Diagnostic workup was unremarkable except for pyuria and minimal albuminuria on urinalysis. In the absence of other risk factors and the temporal relationship between pembrolizumab administration and the onset of acute kidney injury (AKI), immune-related nephrotoxicity was the underlying diagnosis. After initiation of corticosteroids, creatinine decreased back to baseline without the need for kidney biopsy. An addendum to the original pathology report from the outside facility surfaced 5 months after starting treatment, revealing that the second breast lesion had a Fluorescence in situ hybridization (FISH) test performed that was positive. Given this fact, therapy was changed to two cycles of neoadjuvant paclitaxel/carboplatin/trastuzumab/pertuzumab, with approximately 8 weeks between the last pembrolizumab dose and the first dose of trastuzumab. Thereafter, she underwent a right breast mastectomy which showed residual invasive carcinoma with negative margins and lymph nodes. She completed 1 year of trastuzumab. Immune-related AKI is a rare, but potentially serious complication associated with an increase in mortality. Further research is needed in the development and early detection. There is promising research in the development of noninvasive biomarkers which has the added benefit of identifying patients who can be re-challenged with immunotherapy.