Anti-PD1 following ipilimumab for mucosal melanoma: durable tumor response associated with severe hypothyroidism and rhabdomyolysis

Abstract

Treatment with fully human monoclonal antibodies against programmed death 1 (PD1) receptor has shown great promise for a number of advanced malignancies. Although inflammatory adverse events have been well described with anti-CTL antigen 4 (CTLA4) therapy, experience with the range of adverse effects of anti-PD1 remains comparatively limited. Here, we report on a patient with advanced mucosal melanoma who received four doses of MK-3475, a fully human monoclonal antibody against PD1, and experienced a durable near-complete response but developed severe hypothyroidism, rhabdomyolysis, and acute kidney injury. To our knowledge, this is the first case reported of a patient with advanced mucosal melanoma who responded to anti-PD1 therapy. With the promising antitumor effects of anti-PD1 in a wide array of tumors, we expect an increasing number of patients to be exposed to anti-PD1 therapies. Recognition of infrequent presentations of adverse events such as elevated creatine kinase levels and thyroid disorders in patients who receive anti-PD1 therapy is important.

Figure 1. Changes in TSH, CK and ALT levels before and after MK-3475 therapy

The trends of serum levels of TSH (Normal range: 0.5–5 mIU/L) , CK (normal range: 55–170 U/L) and ALT (normal range: 10–50 U/L) were plotted. Time 0 represents the first dose of MK-3475. Time for ipilimumab treatment and radiation therapy are indicated as well. Ipi: ipilimumab.

Figure 2. Tumor response to anti-PD1 immunotherapy

The images of chest CT before, 2 and 14 months after initiation of MK-3475 therapy.