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

Abstract

BACKGROUND:

Metastatic sarcomatoid renal cell carcinoma (sRCC) is an aggressive variant of RCC with generally poor prognosis. Treatment with vascular endothelial growth factor inhibitors or chemotherapy generates only short-lived responses. Recent research has suggested a role for combination checkpoint inhibition as first line treatment for metastatic sRCC. This therapy consists of induction with cytotoxic T-lymphocyte-associated protein 4 inhibitor, ipilimumab, administered with programmed cell death protein 1 (PD-1) inhibitor, nivolumab. After completion of four cycles of combination therapy, single-agent maintenance nivolumab is recommended until progression. Patients who progress on maintenance nivolumab are switched to alternate therapy. Herein, we present a case of a patient with RCC who progressed on maintenance nivolumab who, on retreatment with ipilimumab, demonstrated a significant response In addition, we summarize important findings to support the role of salvage ipilimumab in patients with sRCC.

CASE PRESENTATION:

A 46-year-old man presented with flank pain and hematuria, the work up of which noted a left kidney mass for which he underwent nephrectomy and was diagnosed with localized sRCC with 60% sarcomatoid differentiation. Within 3 months of nephrectomy, he presented with recurrent flank pain and was diagnosed with recurrence of disease. He was treated with ipilimumab 1 mg/kg and nivolumab 3 mg/kg for four doses and demonstrated a partial response. He was then transitioned to single agent nivolumab maintenance. After 3 months on maintenance therapy, he was noted to have progression of disease. Given prior response to immune check point combination, it was decided to rechallenge the patient with 1 mg/kg ipilimumab. After two doses of ipilimumab and nivolumab combination therapy, the patient was noted to have a partial response. He maintained a response for an additional 9 months and treatment was eventually discontinued due to grade 3 toxicity and progression.

CONCLUSIONS:

This case report demonstrates the utility of retreatment with ipilimumab as a salvage option for patients progressing on maintenance PD-1 inhibitors in metastatic RCC. Further studies are needed to identify predictors of response and toxicity to this approach, as well as the optimal scheduling of ipilimumab with maintenance nivolumab.

• Authors: Gemlyn George, Laura Schmidt, Parag Tolat, Mathew Riese, Deepak Kilari
• Journal: Journal for immunotherapy of cancer (J Immunother Cancer) Vol. 8 Issue 1 (02 2020) ISSN: 2051-1426 [Electronic] England
• PMID: 32114501 (Publication Type: Case Reports, Journal Article)
• Copyright: © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Ipilimumab
• Nivolumab

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Renal Cell (drug therapy, immunology, pathology)
• Humans
• Ipilimumab (administration & dosage)
• Kidney Neoplasms (drug therapy, immunology, pathology)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy, immunology, pathology)
• Nivolumab (administration & dosage)
• Retreatment (methods)
• Salvage Therapy (methods)
• Treatment Outcome