Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare distinct subtype of Hodgkin lymphoma (HL) that primarily affects middle-aged men. Given the unique pathological and clinical features of the disease, notably the absence of CD30 expression and CD20 positivity on malignant lymphocyte-predominant cells, the clinical course and treatment paradigm of NLPHL differs from classical HL (cHL).1,2

In a review published in Blood, Dennis A Eichenauer, MD, and Andreas Engert, MD, of the first department of internal medicine at the University of Cologne in Germany, summarized current literature surrounding the treatment of NLPHL.2 They also discussed treatment considerations for two clinical cases at their institution.

Epidemiology, Staging and Prognostic Factors

Overall, NLPHL accounts for an estimated 5% of HL cases, approximately 75% of which exhibit a typical histopathological growth pattern, while 25% have a variant histology.2 Cases with a variant histology are associated with a higher rate of early relapses and overall relapse rate, as well as more advanced disease. Although the histopathological growth pattern has some prognostic utility, it does not influence treatment selection based on currently available evidence.2


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“We do not have any information on whether patients from certain countries or areas are [more] prone to develop NLPHL. Our group does not use population-based registries, but only data from prospective studies that are conducted in Europe,” explained Dr Eichenauer.

“To my knowledge, there are also no analyses from other groups that could show a clear benefit or disadvantage with regard to survival for one race or another,” he said in an email interview.

Table. Risk group allocation as per the German Hodgkin Study Group2

Risk groupDescription
Early stages• Stage I/II without risk factors
Intermediate stages• Stage I/IIA with ≥1 risk factor(s)
• Stage IIB with risk factors C/D, but not A/B
Advanced stages• Stage IIB with risk factors A/BStage III/IV
Risk factors  • Large mediastinal massa
• Extranodal disease
• Elevated erythrocyte sedimentation rateb
• ≥3 nodal areas

aGreater than one third of the maximum horizontal chest diameter
bElevated erythrocyte sedimentation rate: >50 mm/h without B symptoms, >30 mm/h with B symptoms

Most NLPHL patients will present with early-stage disease. The clinical course of the disease is typically indolent, despite a propensity towards late relapses and histological transformation into aggressive B-cell non-Hodgkin lymphoma. The prognosis of the disease is quite favorable, established by evidence of low excess mortality relative to the general population. Among those with a history of NLPHL, lymphoma is not recognized as a leading cause of death.2

Treatment Recommendations for NLPHL

Table. Selected Treatment Recommendations for NLPHL2

Risk CategorySummary of Recommendations
Stage IA NLPHL without clinical risk factors• 1L: Limited-field RT alone at 30 Gy
• 2L: Active surveillance or single-agent anti-CD20 antibody
Early-stage other than stage IA without clinical risk factors and intermediate-stage• 1L: Chemotherapy with 2 cycles (early stages other than stage IA without clinical risk factors) or 4 cycles (intermediate stages) of ABVD followed by limited-field RT at 20 Gy (early stages other than stage IA without clinical risk factors) or 30 Gy (intermediate stages)
• 2L: BR and R-CVP or single-agent anti-CD20 antibody and RT alone
NLPHL in advanced stages• 1L: Conventional chemotherapy ± anti-CD20 antibody
• 2L: R-CHOP
Relapsed NLPHL• Salvage approaches, such as single-agent anti-CD20 antibody, RT alone, or conventional chemotherapy ± anti-CD20 antibody and RT
Histological transformation into aggressive B-cell NHL• R-CHOP or high-dose chemotherapy and ASCT

Abbreviations: ABVD, doxorubicin, bleomycin, vinblastine, dacarbazine; ASCT, autologous stem cell transplantation; BR, bendamustine, rituximab;  RT, radiotherapy; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; R-CVP, rituximab, cyclophosphamide, vinblastine, prednisone; 1L, first-line; 2L, second-line

To read the comprehensive list of recommendations containing qualifying remarks, readers should refer to the full publication in Blood.

Concluding Remarks

“Most knowledge on the treatment of NLPHL derives from subgroup analyses of randomized studies comprising cHL and NLPHL patients, smaller phase II studies and retrospective studies using databases from larger institutions,” the authors wrote.

“Although our recommendations in part differ from other guidelines, including those from the NCCN, we believe that our approach to treat NLPHL is supported by the available data,” they concluded.

References

1. Spinner MA, Varma G, Advani RH. Modern principles in the management of nodular lymphocyte-predominant Hodgkin lymphoma. Br J Haematol. 2019;184(1):17-29. doi:10.1111/bjh.15616

2. Eichenauer DA, Engert A. How I treat nodular lymphocyte-predominant Hodgkin Lymphoma. Blood. Published online September 2, 2020. doi:10.1182/blood.2019004044