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The role of pembrolizumab in relapsed/refractory primary mediastinal large B-cell lymphoma
Sarah Tomassetti1, Robert Chen1, Savita Dandapani2
1City of Hope National Medical Center, Duarte, CA, USA.
Insights
Primary mediastinal large B-cell lymphoma (PMBCL) is a rare DLBCL subtype. Relapsed/refractory PMBCL has limited options, but PD-L1 expression suggests pembrolizumab may be effective.
Area of Science:
- Hematology
- Oncology
- Immunology
Background:
- Primary mediastinal large B-cell lymphoma (PMBCL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL), accounting for about 10% of cases.
- While upfront therapies achieve high cure rates, relapsed/refractory PMBCL (rrPMBCL) presents limited treatment avenues.
- PMBCL shares clinical, pathologic, and genetic similarities with classical Hodgkin lymphoma (cHL), including PD-L1/2 expression.
Purpose of the Study:
- To explore the therapeutic potential of PD-L1 inhibitors, specifically pembrolizumab, for treating relapsed/refractory PMBCL.
- To investigate the role of PD-L1/2 expression in PMBCL as a target for novel immunotherapies.
- To evaluate the efficacy and tolerability of pembrolizumab in rrPMBCL based on its established activity in other malignancies.
Main Methods:
- Review of clinical data and scientific literature regarding PMBCL and cHL.
- Analysis of PD-L1/2 expression patterns in PMBCL.
- Assessment of pembrolizumab's mechanism of action and approved indications.
Main Results:
- PMBCL exhibits significant PD-L1/2 expression, a characteristic shared with cHL.
- Pembrolizumab, a PD-1 inhibitor, has demonstrated efficacy and tolerability in various cancers, including relapsed/refractory cHL.
- Multi-institutional trials are currently evaluating pembrolizumab for rrPMBCL treatment.
Conclusions:
- The PD-L1 expression in PMBCL presents a rationale for targeting this pathway with inhibitors like pembrolizumab.
- Pembrolizumab represents a promising therapeutic option for patients with relapsed/refractory PMBCL.
- Ongoing clinical trials are crucial for establishing the definitive role of pembrolizumab in rrPMBCL management.
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 well-tolerated 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.
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