Immunotherapy may hold promise in treating skin cancer after kidney transplant

The use of immune checkpoint inhibitors given as part of immunosuppressive therapy for kidney transplant patients with advanced skin cancer may be effective and safe, depending on the therapy, two small studies show. It was suggested in

An initial study of 12 kidney transplant recipients with advanced cutaneous squamous cell carcinoma (CSCC) treated with cemiplimab (Rivtayo) plus a mammalian target of rapamycin (mTOR) inhibitor and pulsed corticosteroids was evaluated. Five of 11 possible patients achieved a response (three complete responses, two partial responses), reported Glenn J. Hanna, MD, PhD, of Dana-Farber Cancer Institute in Boston, and colleagues. .

Furthermore, treatment with this regimen did not result in any instances of renal allograft rejection, they stated in their paper. Journal of Clinical Oncology.

“Immune checkpoint inhibitors that target PD-1 are widely used to treat many solid tumor malignancies, but the risk of immune-mediated organ rejection has limited them to date in kidney and other transplant recipients. “It has been excluded from trials investigating its effectiveness,” the authors wrote. “When kidney transplant recipients require anti-PD-1 therapy, the combination of mTOR inhibition and pulsed corticosteroids is the preferred immunosuppressive therapy.”

on the one hand, another study It was also published in Journal of Clinical Oncology The study enrolled eight evaluable kidney transplant recipients with advanced skin cancer who were treated with immunotherapy, but immunosuppressive therapy with the calcineurin inhibitor tacrolimus and prednisone did not lead to allograft rejection in some patients. That was not enough to prevent the reaction, reported Evan J. Lipson, MD, of the Johns Hopkins University Graduate School. M.D. of Baltimore and his colleagues.

In this trial, eight patients were treated with nivolumab (Opdivo) monotherapy combined with low-dose tacrolimus and prednisone. None of these patients achieved a response and 1 experienced allograft loss.

Six of these patients continued to receive ipilimumab (Yervoy) in addition to their original treatment regimen. Of these patients, two achieved complete remission (one with treatment-related allograft loss) and four had progressive disease (one experienced allograft loss).

“While there are important differences between these two trials, together they provide insights that will help clinicians take a major leap forward in elaborating how to best use these drugs in patients.” write Shlomo A. Koifman, MD, and Jessica L. Geiger. Doctor of Medicine at the Cleveland Clinic, Edits accompanying research. “This study…is a landmark trial that addresses an unmet need in an extremely high-risk patient population with limited treatment options.”

However, Dr. Koyfman and Dr. Geiger noted that this is important because some studies have shown that renal allograft failure and return to dialysis are as likely as death, an unacceptable outcome for some patients. He also warned that the treatment was “high risk.”

“Clinicians should therefore carefully counsel patients about this option and feel comfortable offering this treatment to interested patients who are well-informed and have a clear understanding of the risks and benefits.” suggested the researchers.

Hanna and colleagues included 12 patients (median age 62 years, 83% male) who underwent surgery for CSCC, 10 of whom had previously received radiation therapy. The median time since the last kidney transplant surgery was 7.2 years, and 4 patients received two kidney allografts.

In addition to the five patients who responded, two patients had stable disease, resulting in a clinical benefit rate of 64%. Median duration of response was 11.4 months, with continued response in 3 responders.

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

Grade 3 or higher treatment-related adverse events (TRAEs), including diarrhea, infection, and metabolic disturbances, occurred in 5 patients. One patient died from angioedema and anaphylaxis due to mTOR inhibitor crosstaper.

For the study, Lipson et al. included eight evaluable patients (5 with CSCC, 2 with Merkel cell carcinoma, and 1 with melanoma). Median age was 66 years, and 63% were male. Median follow-up was 9.1 months, and mean time since kidney transplantation was 13 years.

Median PFS calculated from the first dose of nivolumab was 1.8 months and PFS after the first dose of ipilimumab and nivolumab was 3 months. With the addition of ipilimumab, the objective response rate was 33.3%, with a duration of response of 6 months and a duration of response of 20.4 months.

The two patients who did not progress to ipilimumab and nivolumab combination therapy died of cancer progression 1.9 and 2.2 months, respectively, after the first dose of nivolumab.

The median OS for the eight patients with an evaluable response was 9.1 months, and the two patients who experienced a complete response each had an OS of 11.3 months and a duration of 31.3 months.

There was one grade 3 TRAE related to nivolumab monotherapy (anemia) and no grade 3 or higher TRAEs related to ipilimumab and nivolumab.