Background Nivolumab (Opdivo™) is a novel IgG4 subclass programmed death-1 (PD-1) inhibiting antibody that has demonstrated breakthrough-designation anti-tumor activity. To date, clinical trials of nivolumab and other checkpoint inhibitors have generally excluded patients with solid organ transplantation and patients with concurrent immunosuppression. However, organ transplant recipients are at high-risk of development of malignancy as a result of suppressed immune surveillance of cancer. Case presentation We illustrate the outcomes of a 63 year-old type I diabetic female patient who developed pulmonary metastatic, BRAF wild-type cutaneous melanoma 10 years after renal transplantation. After downward titration of the patient’s immunosuppressive medications and extensive multidisciplinary review, she was treated with nivolumab in the first-line setting. Within 1 week of administration, the patient experienced acute renal allograft rejection, renal failure and concurrent diabetic ketoacidosis due to steroid therapy. Allograft function did not return, but patient made a full clinical recovery after being placed on hemodialysis. Subsequently, the patient had clinical disease progression off therapy and required re-challenge with nivolumab on hemodialysis, resulting in ongoing clinical and radiographic response. Conclusions This case illustrates multiple practical challenges and dangers of administering anti-PD1 immune checkpoint inhibitors to patients with solid-organ transplantation including need for titration of immunosuppressive medications, risks of allograft rejection, and treatment during hemodialysis.
11 March 2022 in Canadian Urological Association Journal
Background: Ipilimumab and nivolumab (ipi/nivo) improved overall survival (OS) compared to sunitinib in the pivotal Checkmate 214 trial of metastatic renal cell carcinoma (mRCC) with International Metastatic RCC Database Consortium (IMDC) intermediate/poor risk disease. We evaluated the efficacy and toxicity of ipi/nivo in older and frailer populations in a real-world mRCC cohort. Methods: Analysis was conducted on a real-world cohort with mRCC (N = 551) treated with first-line ipi/nivo from the Canadian Kidney Cancer information system (CKCis) database from January 2014 to December 2021. A comparison was made between outcomes and toxicity in patients 1. <70 versus (vs.) ≥70 yo, 2. <75 vs. ≥75 yo, and 3. KPS ≥70 vs. 70 yo and >75 yo when controlled for IMDC. However, when comparing patients with KPS > 70 vs. KPS < 70, patients with a poor performance status had decreased median OS at 54.5 m vs. 10.8 m (p-value < 0.0001) and PFS at 11.6 vs. 3.1 m (p-value < 0.0001). Conclusions: The use of ipi/nivo in mRCC demonstrated similar survival outcomes and toxicity in an older patient population. In patients with a poor performance status, it was associated with inferior OS and PFS. We believe that ipi/nivo is a reasonable treatment option for these patient populations, particularly in older patients.
Approximately 20% of renal cell carcinoma (RCC) is diagnosed because of paraneoplastic manifestations. RCC has been associated with a large variety of paraneoplastic syndromes (PNS), but it is rarely associated with PNS vasculitis. We present a case of a previously healthy male who presented with systemic vasculitis; bitemporal headaches, diplopia, polyarthritis, palpable purpura, tongue lesion, peri-orbital edema, scleritis, chondritis and constitutional symptoms. He was subsequently found to have oligometastatic RCC. Both his primary lesion and site of oligometastasis were treated with stereotactic radiotherapy (SBRT) and resulted in the resolution of his vasculitis, as well as sustained oncologic response. This is the first case to demonstrate that effective sustained treatment for PNS vasculitis due to oligometastatic RCC is possible with SBRT.
The landscape of available therapeutic options for treatment of genitourinary (GU) cancers is expanding dramatically. Many of these treatments have distinct, sometimes severe, skin toxicities including morbilliform, bullous, pustular, lichenoid, eczematous, psoriasiform, and palmoplantar eruptions. Pruritus and skin pigmentation changes have also been noted. This review aims to synthesize dermatologic events observed with antibody drug conjugates, poly (ADP-ribose) polymerase (PARP) inhibitors, androgen receptor pathway inhibitors, tyrosine kinase inhibitors, immune checkpoint inhibitors, and the combination of these agents used for the treatment of GU cancers. It provides a guide on diagnosis and initial management of these rashes for medical oncologists.