Nivolumab Linked to Nephritis in Melanoma

Nivolumab and ipilimumab, new immunotherapies for metastatic melanoma, have both been linked to nephritis. Now, researchers from Centre Hospitalier Lyon-Sud and Université Claude Bernard Lyon in France, report on a patient with melanoma who developed acute interstitial immune nephritis after being treated with nivolumab—not once, but twice.

The patient, a 76-year-old woman with pulmonary metastatic melanoma, was given 4 intravenous cycles of ipilimumab as a first-line treatment. After 16 weeks, the disease was progressing; the ipilimumab was discontinued, and 8 weeks later she was started on second-line treatment with nivolumab. After 3 cycles of nivolumab, she developed acute kidney injury. The patient’s creatinine went from 69 µmol/L before nivolumab to 142 µmol/L before the fourth cycle. Immunotherapy was discontinued.

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The patient had not received any other drug that could explain the increased creatinine level, the researchers say, and she was otherwise asymptomatic. The renal failure persisted despite an adequate fluid intake over 3 days. Biopsy revealed interstitial edema.

The clinicians treated the patient with oral prednisolone, and her renal function rapidly improved, although her creatinine level remained higher than before the nivolumab.

A follow-up CT scan found a partial response to the nivolumab. Based on that reponse, the multidisciplinary staff elected to continue the treatment at the same dose. The fourth cycle was administered while the patient was still receiving daily corticosteroids.

The infusion did not cause kidney failure relapse. However, after the corticosteroids were stopped, the patient’s creatinine level increased gradually, to 158 µmol/L, and again she was hospitalized with relapse of immune interstitial nephritis. The clinicians reinstituted prednisolone, and the acute interstitial nephritis improved. Nivolumab was discontinued.

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Drug-induced acute interstitial nephritis often has been more described with nonsteroidal anti-inflammatory drugs and beta-lactams, among others, the researchers say. Immune interstitial nephritis had been reported in a patient treated with nivolumab and ipilimumab concomitantly, and 3 cases of granulomatous interstitial nephritis have been reported with ipilimumab monotherapy. To the authors’ knowledge, this is the first case of immune interstitial nephritis reported with nivolumab monotherapy in metastatic melanoma. It is important to consider, they add, that the patient had also received ipilimumab, and that due to the drug’s elimination half-life (15.4 days), they can’t exclude an “overlap” between the 2 drugs that might have increased the risk of acute interstitial nephritis.

Source:
Bottlaender L, Breton AL, de Laforcade L, Dijoud F, Thomas L, Dalle S. J Immunother Cancer. 2017;5:56.
doi: 10.1186/s40425-017-0261-2