Salvage ipilimumab associated with a significant response in sarcomatoid renal cell carcinoma

George, Gemlyn; Schmidt, Laura S.; Tolat, Parag; Riese, Mathew; Kilari, Deepak

doi:10.1136/jitc-2020-000584

Cited by 4 publications

(3 citation statements)

References 31 publications

(24 reference statements)

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“…Therefore, CTLA-4 blockade has profound effects on particular T-cell populations important in anti-tumor immunity [32]. George et al reported a case of sarcomatoid RCC that showed partial response to NIVO plus IPI and then progressed during maintenance therapy with NIVO [33], which is very similar to our case. The patient with sarcomatoid RCC was salvaged with the addition of IPI, which may suggest the importance of blocking CTLA-4 as well as PD-1 for sarcomatoid carcinoma.…”

Section: Discussionsupporting

confidence: 85%

Sarcomatoid urothelial carcinoma of the renal pelvis treated with immunotherapy

et al. 2023

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Background Sarcomatoid carcinoma is a rare, high-grade malignancy with epithelial and mesenchymal components. It may be a good candidate for immunotherapy because it is associated with overexpression of programmed cell death ligand 1. Sarcomatoid urothelial carcinoma (UC) of the upper urinary tract is extremely rare. Here we report the first case of sarcomatoid UC of the renal pelvis that responded to immunotherapy. Case presentation A 79-year-old man was referred to our hospital complaining of various symptoms, including anorexia and abdominal pain. A computed tomography scan revealed a right atrial tumor, a 9 cm left renal mass with a renal vein tumor thrombus, para-aortic lymphadenopathy, and multiple small lung nodules. The patient underwent resection of the right atrial tumor. Pathological analysis of the tumor did not lead to an accurate diagnosis even after several rounds of immunohistochemistry. He underwent a needle biopsy of the left kidney and was initially diagnosed with collecting duct carcinoma, a rare subtype of renal cell carcinoma (RCC). Following the initial diagnosis, immunotherapy with nivolumab and ipilimumab commenced. Thereafter, almost all lesions, including the left renal tumor, were reduced in size. However, he underwent a left nephrectomy approximately a year after beginning immunotherapy due to repeated left renal bleeding. Histological examination of the nephrectomy specimen revealed two forms of cancer—sarcomatoid UC and conventional high-grade UC. Two months after surgery, the patient was found to have new lung metastases. He underwent chemotherapy with gemcitabine and cisplatin, followed by immunotherapy with pembrolizumab. However, both treatments were ineffective. The patient died of cancer 19 months after his first admission. Conclusions The presented case of sarcomatoid UC of the renal pelvis that partially responded to immunotherapy suggests that immunotherapy can be a promising treatment for sarcomatoid UC.

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Section: Discussionsupporting

confidence: 85%

Sarcomatoid urothelial carcinoma of the renal pelvis treated with immunotherapy

et al. 2023

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“…In clinical practice, ICI combination therapy would be a better choice 19 , regardless of its complicating immune-related adverse events 20 . Moreover, since patients with mRCC and spindle histology received only a small benefit to survival in our study, ICI combination therapy seems a better strategy 21,22 . Specifically, combination therapy consisting of anti-CTLA-4 (ipilimumab) and anti-PD-1 (nivolumab) may be an optimal choice to treat this formidable disease 23 .…”

Section: Discussionmentioning

confidence: 74%

First-line axitinib therapy is less effective in metastatic renal cell carcinoma with spindle histology

Numakura

Kobayashi

Muto

et al. 2020

Sci Rep

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Axitinib, a vascular endothelial growth factor receptor-tyrosine kinase inhibitor, will be used in combination first-line therapies against metastatic renal cell carcinoma (mRCC), but its effects as a first-line monotherapy are unclear. Thus, we aimed to elucidate pretreatment clinical factors that predict the prognosis of patients with mRCC receiving first-line axitinib therapy. We enrolled 63 patients with mRCC treated with axitinib as first-line therapy between Nov. 2003 and Jul. 2018. Progression-free survival (PFS) and overall survival (OS) were assessed using the Wald χ2 statistic in Cox proportional hazards regression. Median patient age was 67 (range: 25–85) years. Seven (11.1%) patients were classified as being at favorable risk, 33 (52.4%) at intermediate risk, and 23 (36.5%) at poor risk according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification system. Median follow-up duration after axitinib initiation was 14 (range: 1–72) months. Median PFS and OS were 18 months and 65 months, respectively. Cox regression analyses of clinical predictors revealed that high C-reactive protein (CRP) levels were significantly correlated with shorter PFS [hazard ratio (HR), 1.63; 95% confidence interval (CI) 1.7–4.0)], whereas spindle cells and poor IMDC risk scores were related to worse OS (HR, 2.87 and 2.88, respectively; 95% CI 1.4–11.0 and 1.1–8.5, respectively). Thus, patients with mRCC and spindle histology or poor IMDC risk scores had worse OS, and those with high CRP levels had shorter PFS in first-line axitinib treatment. Other therapies might be more suitable for initial management of such patients.

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“…Durable control after cessation of ICI would allow for reintroduction of ICI at the point of progression or recurrence [ 40 ]. Rechallenge with combination anti-CTLA4 and anti-PD1 (e.g., Ipilimumab and Nivolumab) may also be a reasonable option in selected circumstances [ 41 ], which we had done with two patients in this series. The oncologist is challenged to maximize the clinical benefit of ICI therapy by his understanding of the atypical patterns of response.…”

Section: Discussionmentioning

confidence: 99%

Atypical Response Patterns in Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors—Navigating the Radiologic Potpourri

Wong

Vellayappan

Cheng

et al. 2021

Cancers

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Background: Atypical response patterns have been a topic of increasing relevance since the advent of immune checkpoint inhibitors (ICIs), challenging the traditional RECIST (Response Evaluation Criteria in Solid Tumors) method of tumor response assessment. Newer immune-related response criteria can allow for the evolution of radiologic pseudoprogression, but still fail to capture the full range of atypical response patterns encountered in clinical reporting. Methods: We did a detailed lesion-by-lesion analysis of the serial imaging of 46 renal cell carcinoma (RCC) patients treated with ICIs with the aim of capturing the full range of radiologic behaviour. Results: Atypical response patterns observed included pseudoprogression (n = 15; 32.6%), serial pseudoprogression (n = 4; 8.7%), dissociated response (n = 22; 47.8%), abscopal response (n = 9; 19.6%), late response (n = 5; 10.9%), and durable response after cessation of immunotherapy (n = 2; 4.3%). Twenty-four of 46 patients (52.2%) had at least one atypical response pattern and 18 patients (39.1%) had multiple atypical response patterns. Conclusions: There is a high incidence of atypical response patterns in RCC patients receiving ICIs and the study contributes to the growing literature on the abscopal effect. The recognition of these interesting and overlapping radiologic patterns challenges the oncologist to tweak treatment options such that the clinical benefits of ICIs are potentially maximized.

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Salvage ipilimumab associated with a significant response in sarcomatoid renal cell carcinoma

Cited by 4 publications

References 31 publications

Sarcomatoid urothelial carcinoma of the renal pelvis treated with immunotherapy

Sarcomatoid urothelial carcinoma of the renal pelvis treated with immunotherapy

First-line axitinib therapy is less effective in metastatic renal cell carcinoma with spindle histology

Atypical Response Patterns in Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors—Navigating the Radiologic Potpourri

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