The role of pembrolizumab in relapsed/refractory primary mediastinal large B-cell lymphoma

Abstract

Primary mediastinal large B-cell lymphoma (PMBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL). PMBCL comprises approximately 10% of DLBCLs, thus making it a rare variant of DLBCL. Cure rates for PMBCL with upfront regimens like DA-REPOCH exceed 90%. However, if there is a poor response to this first-line therapy, relapsed/refractory PMBCL (rrPMBCL) has limited treatment options. The historic trend is to treat rrPMBCL with salvage regimens commonly used for DLBCL followed by high-dose therapy and autologous stem cell transplant (HDT-ASCT); however, response rates to salvage therapy remain low and few patients are able to proceed to transplant. An interesting feature of PMBCL is that even though it is classified as a subtype of DLBCL, PMBCL actually shares many clinical, pathologic, and genetic features with classical Hodgkin lymphoma (cHL). For example, both frequently express program death ligand 1 and 2 (PD-L1/2), which is not seen in other mature B-cell lymphomas. The expression of PD-L1/2 in PMBCL makes PDL1 inhibitors, such as pembrolizumab, an attractive therapeutic target. Pembrolizumab is an effective and welltolerated therapy now approved for a number of cancer types from advanced melanoma to relapsed/refractory cHL. There are now multi-institutional trials underway assessing the role of pembrolizumab in the treatment of rrPMBCL.

A case of middle mediastinal cavernous hemangioma

“…In the diagnosis of CHM, there are common differential diagnoses: (i) Mediastinal lymphoma: this is a malignant tumor originating from lymphoid tissue, and the common clinical manifestations are cough, hypothermia, fatigue, etc often accompanied by multiple superficial lymph node pain and enlargement, mostly in the incidence of young and middle‐aged. Chest CT features are bilateral paratracheal, posterior sternal and hilar lymph node enlargement.…”

Advancing CAR T-Cell Therapy for Solid Tumors: Lessons Learned from Lymphoma Treatment

“…However, analogous to some trials in solid tumors [79] targeting the VEGF pathway in DLBCL by a combination of bevacizumab with R-CHOP (a chemotherapy regimen used for the treatment of NHL) did not significantly improve outcomes but instead increased toxicity [75]. Lymphoma cells express CD70, CD80, CD86, and PD-L1 immune checkpoints that downregulate effector T-cells including Th17 [80], and that allowed clinical approval of CIs for Hodgkin's lymphoma (HL) and primary mediastinal B-cell lymphoma [81,82]. Cancer-associated fibroblasts (CAFs) promote tumorigenic features of the microenvironment and are often studied merely within the context of bone marrow, as part of multiple myeloma and hairy cell leukemia [83].…”

Treatment of relapsed/refractory paediatric aggressive B‐cell non‐Hodgkin lymphoma

“…Given the expression of PD‐L1/2 on PMBCL cells and its known efficacy in classic Hodgkin lymphoma, pembrolizumab has been tested in adults with heavily pre‐treated r/r PMBCL. Two multicentre phase I (Keynote 013) and phase II (Keynote 170) ongoing studies have shown encouraging ORR rates of 48% and 45% respectively (Zinzani et al , 2017; Armand et al , 2019; Tomassetti et al , 2019). Based on these results, pembrolizumab was recently approved by FDA also for r/r paediatric PMBCL.…”