An 81 year old male with pertinent past history of stage IV Urothelial cancer (CA) was admitted to the hospital in the setting generalized fatigue. Upon interview patient complained of fatigue and myalgia for the past two weeks. Initial laboratory exam revealed he had a Creatine Kinase (CK) level of 7199. Patient did not report any alcohol use, strenuous activity or long-term immobility. He was diagnosed with high grade left renal pelvis Urothelial CA about two years ago. Biopsy confirmed metastatic disease to retroperitoneal (para aortic) and mediastinal nodes. Patient was started on Gemcitabine and Carboplatin, however there was continued progression of his disease as seen on imaging. Due to lack of response to platinum based chemotherapy patient was switched over to Atezolizumab (a programmed cell death ligand “PD-L1” inhibitor). In the hospital he was initially started on intra-venous fluids as well as Prednisone 60 mg twice daily as per Hematology/Oncology recommendations. There was a concern about possible unmasking of an autoimmune process by patient’s current immunotherapy which has been reported with other PD-L1 inhibitors. Hence an extensive workup was sent that consisted of ANA, Extractable Nuclear Antigens (SM, RNP, Ro and La), Anti JO1 IgG AB, Anti-Scleroderma AB, Anti-Smooth Muscle AB, Anti SRP, Anti Mi2 and Anti Ku which all returned negative. Over the course of his hospitalization patient showed symptomatic improvement which correlated with a progressive downward trend of his CK levels. Patient’s current immunotherapy was held he was eventually sent to a post-acute institution for physical rehabilitation.
Discussion:
The basic mechanism of action of a PD-L1 inhibitor is to prevent PD-L1 interaction with PD-1 receptor on the surface of the T-Cells, as in the cancer disease state the interaction of PD-L1 on the cancer cell surface with PD-1 on a T-cell reduces T-cell function. This serves to prevent the immune system from attacking the tumor cells and hence by blocking this interaction there is potential to prevent the cancer from evading the immune system responses. There are several PD-L1 inhibitor antibodies that are being successfully trialed both pre-clinically and within the clinic for use in advanced melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancer and Hodgkin lymphoma etc. Weakness as a result of myasthenia like syndrome as well as unmasking of autoimmune disease have been reported with various PD-L1 inhibitors. Atezolizumab is a monoclonal antibody that was approved in May 2016 for locally advanced or metastatic Urothelial CA. It is an engineered, humanized IgG isotype antibody. Since its recent FDA approval not much data is present about it’s side effects and further characterization is needed for a more complete adverse effect profile.
Conclusions:
Because of lack of response of urothelial CA to platinum based chemotherapy other modalities of treatment assume greater significance. The relative success of PD-L1 inhibitors in treating solid tumors have increased their significance as a future therapeutic option. Atezolizumab a monoclonal AB against PD-L1 on the surface of cancer cell was recently approved by the FDA for localized as well as metastatic Urothelial CA however not much data is available about its adverse effect profile in clinical practice. Muscle breakdown resulting in weakness maybe a potential side effect and further surveillance would be required for affirmation.