Predictive role of PD-L1 expression in the response of renal Medullary carcinoma to PD-1 inhibition

Abstract

BackgroundRenal medullary carcinoma is one of the rarest malignancies arising from the kidney. Despite various aggressive therapeutic regimens, mortality remains significantly high (95%) with a median overall survival of 5 months. Furthermore, the scarcity of this malignancy renders randomized clinical trials impossible. We examined the expression of programmed death ligand 1 (PD-L1) in two new renal medullary carcinoma cases, investigated their responses to the PD-L1 inhibitor nivolumab and explored the predictive role of the rate of PD-L1 expression in such response.Case presentationTwo African-American patients (male and female) with sickle cell trait who presented to our center with hematuria and flank pain were diagnosed with metastatic renal medullary carcinoma. PD-L1 was expressed at rate of 25% and 60% in patient 1 and 2 respectively. Following nephrectomy, they were started on nivolumab. Patient 1 initially responded to the treatment with regression of metastatic lesions. However, following this early response, patient 1 who has been receiving nivolumab for more than 15 months, was noted to have a disease progression. Patient 2 had disease progression after 3 months of nivolumab therapy.ConclusionsAlthough PD-L1 is expressed in these patients with renal medullary carcinoma, response to nivolumab was only observed in patient 1 whose tumor has the lowest rate of PD-L1 expression. This may suggest that in RMC, response to PD-L1 inhibition therapy may not correlate with the rate of PD-L1 expression.

Genomic and Immunologic Characterization of INI1-Deficient Pediatric Cancers

“…Another young adult patient with recurrent INI1-negative renal medullary carcinoma had a complete response to nivolumab lasting greater than nine months despite low TMB (41). Two subsequent adult patients with INI1-negative renal medullary carcinoma treated with nivolumab did not have durable responses (42). A single-arm phase II trial of nivolumab plus ipilimumab in adults with INI1-negative renal medullary carcinoma in adults is now open [NCT03274258] (43).…”

Neurotoxicities associated with checkpoint inhibitors: Two case reports and a review of the literature

“…Although robust data support the use of immunotherapies in many solid tumors, including UC, the efficacy of these agents in renal medullary carcinoma (RMC) is not well established. Published case reports provide a hint of activity in this rare disease . Given the lack of standard treatment options with proven efficacy, an ICI in the setting of a clinical trial is a reasonable approach in this under‐researched population.…”

“…Published case reports provide a hint of activity in this rare disease. 14,15 Given the lack of standard treatment options with proven efficacy, an ICI in the setting of a clinical trial is a reasonable approach in this under-researched population.…”

Renal Medullary Carcinoma

“…PD-L1 was expressed in 23% of tumor cells in this patient. Sodji et al 27 later note that PD-L1 levels may not correlate with the amount of response to nivolumab. In their study of 2 patients with RMC, response to nivolumab was observed only in the patient whose tumor had the lowest rate of PD-L1 expression, present in 25% of tumor cells.…”