ABSTRACT
Introduction: Primary mediastinal large B-cell lymphoma (PMBL) is a rare subtype of lymphoma, clinically and biologically distinct from diffuse large B-cell lymphoma (DLBCL) that shows overlapping features with classical Hodgkin lymphoma (cHL). If first-line strategies lead to 80–85% of curability, relapse occurs early with a chemo-refractory disease and a poor outcome. The presence of 9p24.1 rearrangement, conducting to the overexpression of the immune checkpoint molecules PDL1 and 2, has paved the way for immune checkpoint blockers development in these entities. Pembrolizumab, an anti PD-1 checkpoint antibody, was initially approved in solid cancer and later on in the lymphoma field in cHL.
Areas covered: We summarize the biology and clinical need in PMBL, leading to the rationale for checkpoint inhibitors development, as well as pembrolizumab clinical studies in this entity. To do so, we performed a PubMed search using the terms: ‘PMBCL,’ ‘lymphoma,’ ‘Immune checkpoint,’ and ‘Pembrolizumab.’
Expert opinion: Pembrolizumab showed tolerable safety profile and efficacy data in patients with PMBL who have relapsed after, or are ineligible for autologous stem cell transplant (ASCT). Some combination strategies have shown promising preliminary results, while others are currently being conducted.
Article highlights
PMBCL is a rare subtype of large B-cell lymphoma, with clinical and biological features closely related to cHL. Outcome of relapse and refractory patients is very poor.
There is a strong biological rationale for immune checkpoint blockade in PMBCL, based on recurrent molecular abnormalities leading to immune escape.
Pembrolizumab is an immune checkpoint approved for the treatment of patients with several solid tumors and cHL.
In PMBCL, pembrolizumab has demonstrated a good safety profile and a high overall response rate in both relapsed and refractory patients.
Combination studies with the anti-CD30 drug conjugate showed promising data. Others are warranted and ongoing to improve efficacy and provide further therapeutic options in first line of salvage for these chemo-refractory patients.
Finally, we develop the different biomarkers studies available in the field.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.