Changes in PD-1 and PD-L1 Expression in Cases with Hodgkin Lymphoma after Chemotherapy

PD-1 and PD-L1 expressions in primary refractory and relapse/refractory cases with Hodgkin Lymphoma (HL)

Background and aim: Programmed death 1 (PD-1) pathway has emerged as a mechanism in immune tolerance in various malignant tumors including hemopoietic neoplasias. PD-1 and its ligands PD-L1 and PD-L2 expressions have been detected both on tumor cells and also in the tumor microenvironment/tumor infiltrating cells. Checkpoint inhibitors are the new class of immunotherapy agents and they are monoclonal antibodies targeting PD-1 or PD-L1 and show promising activity in malignant tumors. Generally, but not in all tumors, there is a relationship between response to therapy and PD-1 / PD-L1 expression. Here we wanted to detect the PD-1 and PD-L1 expression before and after treatment in primary refractory HL (PR HL) and relapsed/refractory cases with HL (R/R HL).

Patients and methods: PD-1 and PD-L1 expressions were evaluated in seventeen cases with R/R HL. Female/male ratio was 9/8, age range was between 19 and 59. All cases had classical HL; 12 had nodular sclerosing subtype, 4 had mixed cellular type and subtype could not be determined in one case. Eight cases had PR HL and 9 cases had R/R HL. Immunohistochemistry assay was used to detect PD-1 pathway. More than 5% expression in microenvironment (ME) and/or Reed Sternberg (RS) cells was accepted as positive.

Results:

PR HL cases: PD-1 expression in ME was detected in 2 cases and 4 cases, and in RS cells in none and 2 cases, before and after chemotherapy, respectively. PD-L1 expression in ME was detected in none and 2 cases, and in RS cells in none of the cases, before and after chemotherapy.

R/R HL cases: PD-1 expression in ME was detected in none and 2 cases, and PD-1 expression in RS cells in none and 2 cases, before and after chemotherapy, respectively. PD-L1 expression in ME was detected in 3 and 7 cases, and in RS cells in 2 and 5 cases before and after chemotherapy, respectively.

When we evaluated all cases, we found that PD-1 expression was detected in ME in 4 cases at the beginning and in 8 cases after treatment. PD-1 expression in RS cells was not detected at the beginning while in 4 cases after treatment. PD-L1 expression at the beginning was detected in 3 cases in ME and in 9 cases after treatment. PD-L1 expression at the beginning in ME was detected in 3 cases and in 9 cases after treatment. PD-L1 expression at the beginning in RS cells was detected in 2 cases and after treatment in 5 cases. Table 1 shows the PD-1 and PD-L1 expressions in PR HL and R/R HL cases.

Discussion: PD-1 and/or PD-L1 expressions after treatment are seen in the majority of cases with PR HL and R/R HL both in ME and in RS cells. It is very well known that standard treatment is not clear and there is no good choice in cases with PR HL. On the other hand salvage chemotherapy and high dose chemotherapy/stem cell transplantation is standard in R/R HL cases, but this approach is beneficial in only a limited number of these cases. Brentuximab vedotin is an important molecule in these cases as a bridge for transplantation. In a similar way successfull results have been reported with checkpoint inhibitors in cases with R/R HL. We showed that PD-1/PD-L1 expression is frequent in cases with PR and R/R HL. For this reason both PD-1 or PD-L1 blockade are important therapeutic oppurtunities in cases with PR and R/R HL cases and these agents must be considered in earlier treatment steps of these cases before other too toxic and ineffective chemotherapeutic drugs.