Immunotherapy with checkpoint inhibitors in mismatch repair deficient (dMMR) cancers: Looking for a needle in a haystack— But, joy on finding one.

Abstract

e14073 Background: Pembrolizumab is approved for deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H) metastatic solid tumors with objective response rate (ORR) of 39.6% and response lasting for more than 6 months in 78% patients. Nivolumab is also approved in dMMR metastatic colorectal cancers (mCRC) with ORR of 28% and response lasting greater than 6 months in 67% patients. But finding these patients is difficult as only about 5% of metastatic cancers have dMMR. There is limited data from India in this population. We report our experience with testing and treatment in these patients. Methods: This is a single centre, retrospective study of metastatic solid tumors which had progressed on standard treatment. 137 patients were tested between May 2017 and Dec 2018. MMR testing was done by immunohistochemistry (IHC). The aim was to identify patients with dMMR; and to see their ORR, progression free survival (PFS) at 1 year, and adverse events on treatment with Nivolumab. Results: 137 metastatic cancer patients were tested. 75 had colorectal cancer (mCRC), 30 gastric, 10 hepatobiliary, 10 pancreatic, 8 endometrial, 2 small bowel cancer and 2 had breast cancer. 15 (11%) patients had dMMR. 3 (37%) of endometrium, 5 (16.6%) of stomach, 6 (8%) of mCRC and 1(10%) of hepatobiliary tree cancer had dMMR. 5 of the 15 dMMR patients received immunotherapy with Nivolumab - 2 in mCRC, 2 in stomach and 1 in endometrium. ORR was 60% with 3 partial responses, stable disease was seen in 1 (20%) and progression in 1 (20%). PFS at 1 year was 80%. Treatment was well tolerated.1 patient had hypothyroidism and 1 patient had grade 1 skin toxicity. Conclusions: Testing for dMMR is important in metastatic solid tumors as these patients are ideal for treatment with immunotherapy. But finding dMMR is difficult due to its infrequent presentation, and has been seen in 11% of our unselected patients. We recommend testing for dMMR by IHC in our Indian patients, as this is fast and cost effective. Finding dMMR cancers, and then treating with immunotherapy is rewarding irrespective of the site of origin. High ORR of 60% and 1 year PFS of 80% is very heartening to see in this relapsed metastatic patient group. Treating more dMMR patients and longer followup, will further elucidate the benefit of immunotherapy in our patients.