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The use of immune checkpoint inhibitors given as part of an immunosuppressive regimen for kidney transplant recipients with advanced cutaneous cancers may be effective and safe, depending on the regimen, two small studies suggested.

In the first study among 12 kidney transplant recipients with advanced cutaneous squamous cell carcinoma (CSCC) who were treated with cemiplimab (Libtayo) and a mammalian target of rapamycin (mTOR) inhibitor and pulsed-dose corticosteroids, five of 11 evaluable patients achieved a response (three complete and two partial responses), reported Glenn J. Hanna, MD, of the Dana-Farber Cancer Institute in Boston, and colleagues.

Moreover, treatment with the regimen resulted in no instances of kidney allograft rejection, they noted in the .

"Immune checkpoint inhibitors targeting PD-1 are widely used to treat many solid tumor malignancies, but the risk of immune-mediated organ rejection has previously excluded kidney and other transplant recipients from trials investigating their efficacy," the authors wrote. "Combining mTOR inhibition and pulsed corticosteroids is a favorable immunosuppressive regimen when kidney transplant recipients require anti-PD-1 therapy."

On the other hand, in also published in the that involved eight evaluable kidney transplant recipients with advanced skin cancer treated with immunotherapy, an immunosuppressive regimen of the calcineurin inhibitor tacrolimus and prednisone was insufficient to prevent allograft rejection in some patients, reported Evan J. Lipson, MD, of the Johns Hopkins University School of Medicine in Baltimore, and colleagues.

In this trial, the eight patients were treated with nivolumab (Opdivo) monotherapy with concurrent low-dose tacrolimus and prednisone. None of these patients achieved a response, and one experienced allograft loss.

Six of these patients went on to receive ipilimumab (Yervoy) in addition to the original treatment regimen. Of these patients, two achieved a complete response (one with treatment-related allograft loss), while four had progressive disease (with one experiencing allograft loss).

"These two trials have important differences, but taken together, provide insight that can help clinicians take a giant leap forward in elaborating how to best use these agents in these patients," wrote Shlomo A. Koyfman, MD, and Jessica L. Geiger, MD, both of the Cleveland Clinic, in an . "The studies ... are landmark trials that address an unmet need in an extremely high-risk patient population with limited therapeutic options."

However, Koyfman and Geiger also warned that the "stakes are high" with these treatments, since the potential for renal allograft failure and a return to dialysis have been equated to death in some studies, and would be unacceptable outcomes to some patients.

"Clinicians should therefore carefully counsel their patients on this option and feel comfortable to offer this regimen to interested patients who are well informed and have a clear understanding of the risks and benefits," they suggested.

Hanna and colleagues included 12 patients (median age 62 years, 83% men) who had undergone surgery for CSCC, with 10 previously receiving radiation therapy. Median time from the last kidney transplant surgery was 7.2 years, with four patients having received two kidney allografts.

In addition to the five patients who had a response, two patients had stable disease, for a clinical benefit rate of 64%. Median duration of response was 11.4 months, and was ongoing among three responders.

At a median follow-up of 6.8 months, median progression-free survival (PFS) was 22.5 months. Median overall survival (OS) was 22.5 months, with a 3-month estimated OS rate of 72%. Five patients had died at the time of data cutoff.

Grade ≥3 treatment-related adverse events (TRAEs) occurred in five patients, including diarrhea, infection, and metabolic disturbances. One patient died of angioedema and anaphylaxis attributed to mTOR inhibitor cross-taper.

For their study, Lipson and colleagues included eight evaluable patients (five with CSCC, two with Merkel cell carcinoma, and one with melanoma). Median age was 66 years, and 63% were men. Median follow-up was 9.1 months, and mean time from kidney transplantation was 13 years.

Median PFS was 1.8 months, calculated from the first dose of nivolumab, while the PFS since receiving the first dose of ipilimumab and nivolumab was 3 months. The objective response rate was 33.3% with the addition of ipilimumab, with a duration of response of 6 months and one ongoing at 20.4 months.

The two patients who did not transition to ipilimumab plus nivolumab died of cancer progression at 1.9 and 2.2 months, respectively, after first administration of nivolumab.

Median OS for the eight response-evaluable patients was 9.1 months, while OS for the two patients who experienced a complete response was 11.3 months and ongoing at 31.3 months, respectively.

There was one grade 3 TRAE related to nivolumab monotherapy (anemia), and no grade ≥3 TRAEs related to ipilimumab plus nivolumab.