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13-07-2022 | Immunotherapy | News

ICI therapy feasible in advanced cancer patients with kidney transplant using immunosuppression

Author: Lynda Williams

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medwireNews: Discontinuation of immunosuppressive therapy may not be required for patients with a kidney transplant receiving immune checkpoint inhibitor (ICI) therapy for advanced cancer, indicates preliminary research published in The Lancet Oncology.

“Our results suggest that kidney transplant recipients with cancer who maintain their baseline level of immunosuppression have responses to immune checkpoint inhibition similar to those observed in the general population of patients with cancer, but that organ rejection rates are lower than in previously published reports,” write Robert Carroll (Royal Adelaide Hospital, South Australia) and co-authors.

Their phase 1 study included 17 patients with incurable, locally advanced or metastatic tumors, namely cutaneous cell carcinoma (35%) or squamous cell carcinoma (18%) of the head and neck, cancers of the kidney (12%), liver (6%), lung (6%), or colon (6%), Merkel cell carcinoma (12%), or melanoma (6%) from three Australian hospitals.

The patients had received a kidney allograft at least 3 months earlier, and had a creatinine concentration below 180 mmol/L and a low concentration of donor-specific HLA antibodies, the researchers report.

Overall, 13 patients were given nivolumab as per the trial protocol, two patients received the PD-1 inhibitor outside the trial, and two individuals received either avelumab or cemiplimab.

The team explains that around 70 days after the final patient received an ICI the study was closed due to the COVID-19 pandemic.

Overall, 24% of patients had a complete response to treatment and 29% achieved a partial response, with a median duration of response of 27.7 months.

None of the 17 individuals met the primary endpoint of irretrievable allograft loss without tumor response, the team reports.

The median durations of overall and progression-free survival were 3.2 and 2.5 months, respectively, and at 2 years 89% of the nine surviving patients continued to have a functioning allograft.

However, two patients with squamous cell carcinoma of the head and neck who received nivolumab outside of the study protocol and achieved a complete and partial response, respectively, subsequently discontinued ICI therapy following allograft rejection.

Anti-thymocyte globulin and plasma exchange successfully treated moderate T-cell mediated rejection with mild intimal arteritis and borderline cellular rejection in one patient but not in the second patient who lost their allograft after developing severe T-cell mediated rejection.

A third patient with bladder cancer lost their allograft on day 300, after 10 nivolumab infusions, following a renal parenchymal bleed during ureteric stent placement that was exacerbated by prophylactic warfarin use and which the researchers observe was related to the procedure and “not directly to nivolumab.”

Noting that concentrations of the urinary inflammatory chemokine IP-10 were elevated before nivolumab initiation in both the patients who experienced allograft rejection, the investigators suggest that testing for this could flag subclinical rejection. But they emphasize that this was an exploratory endpoint and “larger studies investigating this molecule are required.”

The authors of a linked comment say that “this first prospective study in kidney transplant recipients fills a gap and is greatly welcomed,” but add that “it is not devoid of methodological limitations.”

Céleste Lebbé (Université Paris Cité, France) and co-authors observe that the investigators chose patients “with a possible bias toward malignancies that are highly responsive to immune checkpoint inhibitors,” and that 41% of the patients were given their ICI as a first-line systemic treatment for nodal metastases.

“These limitations should prompt caution in the comparison of efficacy across studies and encourage the design of tumour-specific trials,” they advise.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

Lancet Oncol 2022; doi: 10.1016/S1470-2045(22)00368-0
Lancet Oncol 2022; doi: 10.1016/S1470-2045(22)00395-3

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