Data indicate that nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity accounting for approximately 5% of all Hodgkin lymphoma (HL) cases. The incidence is roughly 0.1-0.2 cases per 100,000 people per year. NLPHL is characterized by a consistent expression of CD20 on the malignant lymphocyte-predominant cells and a rather indolent clinical course. At present, there is no accepted standard of care for the first-line treatment of NLPHL.

To shed more light on the long-term outcomes of patients with NLPHL who were initially treated with stage-adapted HL-directed approaches, we and our colleagues performed a subgroup analysis of nine consecutive randomized phase III trials conducted between 1993 and 2008. For our report published in Journal of Clinical Oncology, 471 patients with NLPHL were taken into account. Treatment consisted of ABVD-based chemotherapy [doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine] followed by consolidation radiotherapy for early and intermediate stages and different BEACOPP [bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, prednisone] variants optionally followed by consolidation radiotherapy of larger residual lymphoma for advanced stages. Anti-CD20 antibodies were not given.

At 10 years, the progression-free survival and overall survival estimates were 75.5% and 92.1%, respectively. Thus, outcomes were comparable with those obtained from patients with classical HL. Risk factors associated with impaired outcomes were age 45 and older and liver, bone marrow, and splenic involvement. Of documented deaths, 23.3% were due to NLPHL, whereas most were caused by second primary malignancies or non-malignant conditions.

Taken together, our analysis indicates an excellent efficacy of stage-adapted HL-directed treatment approaches in patients with NLPHL. Therefore, HL-directed therapy can be considered in patients with newly diagnosed NLPHL. However, a reduction of treatment intensity without a significant loss of efficacy should represent the major goal for future studies in this rare disease, given the low lymphoma-specific mortality on one hand and relevant late effects that can be caused by conventional chemotherapy and radiotherapy on the other hand. Possible approaches to achieve this goal could be the implementation of targeted drugs, such as anti-CD20 antibodies and treatment guidance according to interim positron emission tomography.