Side effects of immunotherapy - Part 7

Previous post:  Side effects to immunotherapy: Part 6   Continuing....

 Persistently curly hair phenotype with the use of nivolumab for squamous cell lung cancer. 

 Dasanu, Lippman, Plaxe.  J Oncol Pharn Pract. 2016 Oct 18.

Increasing use of programmed cell death protein 1/programmed cell death protein 1 ligand inhibition for the treatment of patients with various malignancies such as advanced lung cancer, kidney cancer, and melanoma has resulted in valuable clinical responses, along with the occurrence of new and often puzzling side effects. Known cutaneous effects of CTLA4 and programmed cell death protein 1/programmed cell death protein 1 ligand inhibitors include generalized pruritus, vitiligo, maculopapular lesions, and lichenoid skin eruptions. Alopecia has been the only hair effect previously associated with this class of agents. We describe herein the first case of a persistent curly hair phenotype with the use of nivolumab in a patient with metastatic squamous cell lung cancer.

Vasculitic Neuropathy induced by Pembrolizumab.   Aya, Ruiz-Esquide, Viladot, et al. Ann Oncol. 2016 Nov 17.

Atrophic Exocrine Pancreatic Insufficiency Associated with Anti-PD1 Therapy.  Long, Hoadley, Sandanayake.  Ann Oncol. 2016 Nov 17. 

PD-1 Antibody-induced Guillain-Barré Syndrome in a Patient with Metastatic Melanoma.

Schneiderbauer, Schneiderbauer, Wick, et al.  Acta Derm Venereol. 2016 Oct 14. 

Autoimmune Cardiotoxicity of Cancer Immunotherapy. Cheng, Loscalzo. Trends Immunol. 2016 Dec 2.
Contemporary immunotherapies (e.g., immune checkpoint inhibitors), which enhance the immune response to cancer cells, improve clinical outcomes in several malignancies. A recent study reported the cases of two patients with metastatic melanoma who developed fatal myocarditis during ipilimumab and nivolumab combination immunotherapy; these examples highlight the risk of unbridled activation of the immune system.

Autoimmune Hemolytic Anemia as a Complication of Nivolumab Therapy. Palla, Kennedy, Mosharraf, Doll. Case Rep Oncol. 2016 Nov 7.

Recently, immunotherapeutic drugs, including PD-1 inhibitors (nivolumab, pembrolizumab), PD-L1 inhibitors (atezolizumab, avelumab), and CTLA4 inhibitors (ipiliumumab), have emerged as important additions to the armamentarium against certain malignancies and have been incorporated into therapeutic protocols for first-, second-, or third-line agents for these metastatic cancers. Immune checkpoint inhibitor nivolumab is currently FDA approved for the treatment of patients with metastatic malignant melanoma, metastatic non-small cell lung cancer, metastatic renal cell cancer, and relapsed or refractory classic Hodgkin's lymphoma. Given the current and increasing indications for these drugs, it is essential for all physicians to become well versed with their common adverse effects and to be observant for other less documented clinical conditions that could be unmasked with the use of such medications. A definite association between autoimmune hemolytic anemia and the immune checkpoint inhibitor nivolumab has not been clearly documented, although a few cases have been reported recently. We report a case of fatal autoimmune hemolytic anemia refractory to steroids in a patient treated with nivolumab for metastatic lung cancer, and reflect on the other reported cases of autoimmune hemolytic anemia after the use of nivolumab.

Sarcoidosis in the setting of combination ipilimumab and nivolumab immunotherapy: a case report & review of the literature. Ruess, Kunk, Stowman, et al. J Immunother Cancer. 2016 Dec 20.

We report a case of sarcoidosis in a patient with metastatic melanoma managed with combination ipilimumab/nivolumab. Sarcoid development has been linked with single agent immunotherapy but, to our knowledge, it has not been reported with combination ipilimumab/nivolumab treatment. This case raises unique management challenges for both the melanoma and the immunotherapy-related toxicity.  A 46 year old Caucasian female with M1c-metastatic melanoma was managed with ipilimumab/nivolumab combination. Patient experienced response in baseline lesions but developed new clinical and radiographic findings. Biopsy of new lesions at two different sites both demonstrated tumefactive sarcoidosis. Staining of the biopsy tissue for PD-L1 expression demonstrated strong PD-L1 staining of the histiocytes and lymphocytes within the granulomas. Monotherapy nivolumab was continued without progression of sarcoid findings or clinical deterioration.  Tissue biopsy for evaluation of new lesions on immunotherapy is an important step to help guide decision making, as non-melanoma lesions can mimic disease progression.

Not trying to alarm anyone!!!  With melanoma you gotta get treatment!  And sadly, knowledge of side effects cannot necessarily prevent them.  Still,  forewarned may allow you to be forearmed in recognizing a problem so that it can be dealt with before it causes additional harm!

All my best, c