There may be alternative approaches to scoring matches , especially in the case of immunotherapy , as one drug may be used in some circumstances to theoretically target multiple genomic alterations . It is becoming increasingly evident that immune checkpoint blockade and genomics are not separate silos , but rather linked to each other . This is because abnormalities in DNA damage repair and DNA replication can result in increased rates of somatic mutations in tumors . In turn , the presentation of neo - antigens generated by the mutanome in combination with immune system activation by checkpoint blockade can distinguish normal from tumor tissue . Based on studies demonstrating a relationship between TMB and immunotherapy response ( i.e. , the higher the TMB , the greater the response rate ) and between other gene alterations , such as PDL1 amplification and response , genomics is directly relevant to selecting patients for immune checkpoint blockade . 17,43 Furthermore , the FDA has approved the immune checkpoint inhibitor , pembrolizumab , for any solid tumor with alterations in DNA mismatch repair pathway genes ( e.g. ,MSH2 , MSH6 , MLH1 , PMS2 ) due to associated large increases in TMB . 35 Moreover , TMB increases correlate with a higher neoantigen load based upon somatic mutation data from the TCGA . 44 In turn , these would be expected to be more immunogenic and therefore responsive to immunotherapy . 17 In a retrospective fashion that was unblinded to outcomes , we developed an alternative approach for scoring immune checkpoint blockade matches . In a histology agnostic fashion , we previously reported objective response rates ( ORR , % ) for patients receiving immunotherapy in the setting of low , intermediate , and high TMB . 17 Therefore , we adopted these ORRs as the matching scores for intermediate TMB ( given under the I - PREDICT protocol ( PFS2 ) ; ( iii ) PFS2 versus PFS1 ( immediate prior line of therapy using patients as their own control ) , 7,46 ; ( iv ) percent of patients with a PFS2 / PFS1 ratio ≥1.3 ; 7 and ( v ) overall survival ( OS ) . SD , PR , or CR was initially determined per the assessment of the treating physician . Patients with ongoing SD for less than six months at the date of data cut off were considered inevaluable for the DCR . However , they were evaluable for PFS and OS . PFS was defined as the time from the beginning of therapy to disease progression , or the time to last follow up for patients that were progression - free ( patients that were progression - free on the date of last follow up were censored on that date ) . OS was defined as the time from the beginning of therapy to death , or last follow - up date for patients who were alive ( the latter were censored on that date ) . The cut - off date of the analysis was August 15 , 2017 and cut - off date for patients included was consent by end of June 2017 .