 Good morning. My name is Yana Najjar. I'm a resident and internal medicine at the Cleveland Clinic I'd like to thank the KCA organizing committee for the opportunity to present our case and Today we'll be talking about novel immunotherapy in the setting of metastatic renal cell carcinoma. I Have no disclosures So our case begins with a 53-year-old gentleman who for the past several months had been having small volume homoptysis He was otherwise entirely asymptomatic He had a CT chest done at the outside hospital and that showed some right hyaluradenopathy the largest node measured 27 by 26 millimeters He had a biopsy done at the outside hospital also and that was non-diagnostic. We did not have access to those reports You can see here imaging of the CT abdomen and pelvis in our patients He had a sizable mass that was pretty classic in appearance for renal cell carcinoma History-wise this gentleman had a past medical history of dyslipidemia, which was well controlled with Simba Stanton He had CAD. He had required a PCA to the LAD several years prior He had never been a smoker. He didn't drink alcohol and he had no occupational exposure. This family history was not contributory This gentleman initially underwent a laparoscopic left radical nephrectomy Pathology showed clear cell carcinoma grade three out of four There was evidence of invasion into the sinus fat and the renal vein and also some evidence of lymphovascular invasion And at that point this gentleman was started on synitinib 50 milligrams a day on the standard schedule of One month on and two weeks off of therapy He did very well for two years, but at that point imaging did show evidence of Progressive disease specifically in the liver multiple intraabdominal and intrapelvic lymph nodes And in the nephrectomy bed and at this point He was started on phase one trial of Nevo with synitinib-pizopinib or ipilimumab and he was randomized to the Nevo and ipi arm You can see here baseline measurements. This gentleman's total tumor burden was 10.8 centimeters and six weeks after the initiation of therapy This had increased by 1.2 centimeters. So he had an increase in 11 percent of his total tumor burden Toxicity at this point was great to constipation great to anemia He did endure some fatigue and he was starting to have lower GI bleeding Which we presumed was on hemorrhoids as these were present on physical exam Subjectively he did tell us that he was feeling a lot better His appetite was back at baseline his energy level was pretty good And he had had a subcutaneous flank tumor that he felt was shrinking You can see here comparisons Baseline imaging and then after six weeks in the left nephrectomy bed and the mass and that nephrectomy bed is appreciably larger on imaging The question at this point became what to do next should we take him off of trial with Nevo and ipi and put him on a third line agent Should we stop his treatment entirely and enroll him in hospice or should we continue treatment with his current therapy? it was decided to continue this patient on ipi and Nevo and Eight weeks later so two weeks after he had had his third dose of treatment his toxicity was getting worse He was still having great to constipation and fatigue His appetite was pretty much gone. He was losing weight rapidly and He was still having lower GI bleeding much more frequently and it was causing him great to anemia Again, it was presumed to be from hemorrhoids at this point He was also having LFT abnormalities his ALT AST and alfos were all elevated We wanted to further work up this GI bleeding especially in the setting of the LFT abnormalities We were concerned for colitis, so he had a colonoscopy and at that point there was a 4 centimeter mass 15 biopsies were taken only one out of the 15 showed a very small focus of clear cell carcinoma His LFT abnormalities improved quite rapidly on 40 milligrams of prednisone a day and Overall he started to feel better. He improved clinically Again, you can see the measurements here at baseline and then at six weeks as we had said a tumor had initially grown To 12 centimeters total burden at 12 weeks though You can see that his total burden is down to 9.3 centimeters Giving him a 14 percent reduction at 18 weeks He had total volume reduction to 7.7 centimeters bringing him down to 29 percent compared to his baseline at 16 weeks Prior to the patient being scheduled to go to the OR for a section of this large polyp that we had just discussed He had a colonic into sepsion and he had to emergently be taken to the OR for a partial left colactomy And at that point pathology showed that the clear cell carcinoma was invading the full thickness of the colonic mucosa All of his lymph nodes are clear six out of six had no evidence of disease At this point the patient is still on treatment He is tolerating it very well. His energy is improved. His appetite is back. He put on the weight He had initially lost He is back to working part-time and he's back to all of his regular activities He is off of prednisone all of his labs have normalized and the only toxicity at his last visit Which was just under 10 days ago was grade 1 anemia Thank you for your attention