Nodular lymphocyte-predominant Hodgkin lymphoma: advances in disease biology, risk stratification, and treatment

Abstract

Recent updates have detailed how patients with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) may be better risk stratified using prognostic scoring systems. Most patients with NLPHL present with early-stage disease and have an indolent disease course. To reflect these differences from classic Hodgkin lymphoma, nomenclature has been updated to recognize nodular lymphocyte-predominant B-cell lymphoma as an alternative to NLPHL. The Global NLPHL One Working Group have published their pivotal dataset in 2024 which challenges the prognostic significance of variant immunoarchitectural (IAP) patterns and proposes a new prognostic scoring system. Key identified prognostic factors include age >45 years, stage III-IV disease, hemoglobin <10.5 g/dL and splenic involvement. After multivariate analysis, variant IAP was not shown to be associated with inferior outcome. As most patients with NLPHL have excellent long-term survival, identifying patients where treatment de-escalation is appropriate will help to minimize toxicity. De-escalation strategies include observation after fully resected stage I disease, active surveillance, anti-CD20 antibody monotherapy, radiotherapy in early-stage disease, and avoiding anthracycline- or bleomycin-containing chemotherapy regimens. Evidence supporting the use of novel therapies remains limited with disappointing results from a recently published study of ibrutinib in patients with relapsed NLPHL. Hopefully, future trials will investigate novel agents such as checkpoint inhibitors, T-cell engaging antibodies and chimeric antigen receptor T-cell therapy.

Figure 1.

Characteristic histologic images of lymph node sections in patients with nodular lymphocyte-predominant Hodgkin lymphoma. Hematoxylin and eosin stain of a lymph node with partial effacement by nodular lymphocyte-predominant Hodgkin lymphoma, pattern A (B-cell rich nodular), at 5x magnification (A) and at 60x magnification (B) with lymphocyte-predominant (LP) cells peppered among small mature lymphocytes. (C) Immunohistochemistry for OCT2 shows accentuated nuclear staining of LP cells within B-cell rich nodules with weaker staining of small mantle-type B cells. (D) In comparison to (C), OCT2 staining in an area of growth pattern E demonstrates nuclear staining of LP cells diffusely scattered in a milieu composed of predominantly mature T cells and histiocytes.

Figure 2.

Proposed treatment algorithm. ^#Number of; R-CVP: rituximab, cyclophosphamide, vincristine, prednisolone; R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone; BR: bendamustine, rituximab; R-ABVD: rituximab, doxorubicin, bleomycin, vinblastine, dacarbazine, RT: radiotherapy; IAP: immunoarchitectural pattern. *Recommendation that number of cycles of chemotherapy is discussed at a multidisciplinary team (MDT) meeting.