A Patient With Diabetes, Renal Disease, and Melanoma

Patients who are on hemodialysis and who have cancer present a “unique challenge,” say clinicians from Dartmouth-Hitchcock in New Hampshire.

Patients with end-stage renal disease (ESRD) are at risk of drug accumulation and toxicity. Many anticancer drugs and their metabolites are excreted by the kidney, but data to guide dose and schedule adjustments in renal dialysis are “scant,” the clinicians say. They cite a study that found 72% of dialysis patients receiving anticancer drugs needed dosage adjustments for at least 1 drug. The study researchers also found a significant number of chemotherapy drugs for which there were no available recommendations in dialysis patients.

However, a safe and effective alternative for these patients may exist. The clinicians report on a case—to the best of their knowledge, the first such—of a patient with metastatic melanoma who was successfully treated with pembrolizumab while on hemodialysis.

The patient, who had diabetes and ESRD, also had melanoma in his ear, which metastasized. After discussing his therapeutic options—including the limited data on available immunotherapy drugs—clinicians and the patient agreed to proceed with pembrolizumab, an IgG4-κ human antiprogrammed cell death protein 1 (PD-1) monoclonal antibody. Pembrolizumab has been shown to improve survival rates in patients with melanoma, although it had not been reported in patients with melanoma on dialysis.

The patient received pembrolizumab 2 mg/kg/dose, repeated every 3 weeks. After 1 dose, his abdominal pain and appetite improved. Serum lactate dehydrogenase dropped from 1,182 to 354 units/L. He continued on dialysis 3 times a week with stable serum creatinine levels. After 3 cycles, the computerized tomography scan showed the pulmonary nodules had resolved,  and retroperitoneal lymphadenopathy was significantly reduced. After 10 cycles, he was in complete remission.

Pembrolizumab has distinct benefits for patients like theirs, the clinicians suggest. For one, the molecular weight of the antibody means it is not dialysable, so ultrafiltration (reducing drug exposure) is not the issue it might be. The drug can likely be given without regard to the timing of dialysis. Another benefit for these patients who are usually immunocompromised is that PD-1 antibodies “disrupt” the interactions that create an “immune-suppressive tumor microenvironment” and allow T-cell antitumor activity, the clinicians say.

Their report demonstrates that PD-1 antibodies can be effective in dialysis-dependent ESRD, they say, but add that further research into the induced immune response is warranted. In clinical trials, a small number of patients on pembrolizumab (0.4%) developed immune-mediated nephritis. That might not be as crucial for patients who are already on hemodialysis, the clinicians note, but they caution that the adverse effect (AE) could be a risk for patients with normal renal function or chronic kidney disease. However, their patient experienced no pembrolizumab-related AEs other than mild fatigue.

Source:

Chang R, Shirai K. BMJ Case Rep. 2016; pii: bcr2016216426.

doi: 10.1136/bcr-2016-216426.

Patients who are on hemodialysis and who have cancer present a “unique challenge,” say clinicians from Dartmouth-Hitchcock in New Hampshire.

Patients with end-stage renal disease (ESRD) are at risk of drug accumulation and toxicity. Many anticancer drugs and their metabolites are excreted by the kidney, but data to guide dose and schedule adjustments in renal dialysis are “scant,” the clinicians say. They cite a study that found 72% of dialysis patients receiving anticancer drugs needed dosage adjustments for at least 1 drug. The study researchers also found a significant number of chemotherapy drugs for which there were no available recommendations in dialysis patients.

However, a safe and effective alternative for these patients may exist. The clinicians report on a case—to the best of their knowledge, the first such—of a patient with metastatic melanoma who was successfully treated with pembrolizumab while on hemodialysis.

The patient, who had diabetes and ESRD, also had melanoma in his ear, which metastasized. After discussing his therapeutic options—including the limited data on available immunotherapy drugs—clinicians and the patient agreed to proceed with pembrolizumab, an IgG4-κ human antiprogrammed cell death protein 1 (PD-1) monoclonal antibody. Pembrolizumab has been shown to improve survival rates in patients with melanoma, although it had not been reported in patients with melanoma on dialysis.

The patient received pembrolizumab 2 mg/kg/dose, repeated every 3 weeks. After 1 dose, his abdominal pain and appetite improved. Serum lactate dehydrogenase dropped from 1,182 to 354 units/L. He continued on dialysis 3 times a week with stable serum creatinine levels. After 3 cycles, the computerized tomography scan showed the pulmonary nodules had resolved,  and retroperitoneal lymphadenopathy was significantly reduced. After 10 cycles, he was in complete remission.

Pembrolizumab has distinct benefits for patients like theirs, the clinicians suggest. For one, the molecular weight of the antibody means it is not dialysable, so ultrafiltration (reducing drug exposure) is not the issue it might be. The drug can likely be given without regard to the timing of dialysis. Another benefit for these patients who are usually immunocompromised is that PD-1 antibodies “disrupt” the interactions that create an “immune-suppressive tumor microenvironment” and allow T-cell antitumor activity, the clinicians say.

Their report demonstrates that PD-1 antibodies can be effective in dialysis-dependent ESRD, they say, but add that further research into the induced immune response is warranted. In clinical trials, a small number of patients on pembrolizumab (0.4%) developed immune-mediated nephritis. That might not be as crucial for patients who are already on hemodialysis, the clinicians note, but they caution that the adverse effect (AE) could be a risk for patients with normal renal function or chronic kidney disease. However, their patient experienced no pembrolizumab-related AEs other than mild fatigue.

Source:

Chang R, Shirai K. BMJ Case Rep. 2016; pii: bcr2016216426.

doi: 10.1136/bcr-2016-216426.

Patients who are on hemodialysis and who have cancer present a “unique challenge,” say clinicians from Dartmouth-Hitchcock in New Hampshire.

Patients with end-stage renal disease (ESRD) are at risk of drug accumulation and toxicity. Many anticancer drugs and their metabolites are excreted by the kidney, but data to guide dose and schedule adjustments in renal dialysis are “scant,” the clinicians say. They cite a study that found 72% of dialysis patients receiving anticancer drugs needed dosage adjustments for at least 1 drug. The study researchers also found a significant number of chemotherapy drugs for which there were no available recommendations in dialysis patients.

However, a safe and effective alternative for these patients may exist. The clinicians report on a case—to the best of their knowledge, the first such—of a patient with metastatic melanoma who was successfully treated with pembrolizumab while on hemodialysis.

The patient, who had diabetes and ESRD, also had melanoma in his ear, which metastasized. After discussing his therapeutic options—including the limited data on available immunotherapy drugs—clinicians and the patient agreed to proceed with pembrolizumab, an IgG4-κ human antiprogrammed cell death protein 1 (PD-1) monoclonal antibody. Pembrolizumab has been shown to improve survival rates in patients with melanoma, although it had not been reported in patients with melanoma on dialysis.

The patient received pembrolizumab 2 mg/kg/dose, repeated every 3 weeks. After 1 dose, his abdominal pain and appetite improved. Serum lactate dehydrogenase dropped from 1,182 to 354 units/L. He continued on dialysis 3 times a week with stable serum creatinine levels. After 3 cycles, the computerized tomography scan showed the pulmonary nodules had resolved,  and retroperitoneal lymphadenopathy was significantly reduced. After 10 cycles, he was in complete remission.

Pembrolizumab has distinct benefits for patients like theirs, the clinicians suggest. For one, the molecular weight of the antibody means it is not dialysable, so ultrafiltration (reducing drug exposure) is not the issue it might be. The drug can likely be given without regard to the timing of dialysis. Another benefit for these patients who are usually immunocompromised is that PD-1 antibodies “disrupt” the interactions that create an “immune-suppressive tumor microenvironment” and allow T-cell antitumor activity, the clinicians say.

Their report demonstrates that PD-1 antibodies can be effective in dialysis-dependent ESRD, they say, but add that further research into the induced immune response is warranted. In clinical trials, a small number of patients on pembrolizumab (0.4%) developed immune-mediated nephritis. That might not be as crucial for patients who are already on hemodialysis, the clinicians note, but they caution that the adverse effect (AE) could be a risk for patients with normal renal function or chronic kidney disease. However, their patient experienced no pembrolizumab-related AEs other than mild fatigue.

Source:

Chang R, Shirai K. BMJ Case Rep. 2016; pii: bcr2016216426.

doi: 10.1136/bcr-2016-216426.