Incorporating Monoclonal Antibodies into the First-Line Treatment of Classical Hodgkin Lymphoma

Abstract

The long-term survival of Hodgkin lymphoma (HL) patients treated according to the current standard of care is excellent. Combined-modality schedules (ABVD plus radiotherapy) in early-stage disease, along with treatment intensity adaptation to early metabolic response assessed by PET/CT in advanced stage HL, have been the cornerstones of risk stratification and treatment decision-making, minimizing treatment-related complications while keeping efficacy. Nevertheless, a non-negligible number of patients are primary refractory or relapse after front-line treatment. Novel immunotherapeutic agents, namely Brentuximab Vedotin (BV) and immune checkpoint inhibitors (CPI), have already shown outstanding efficacy in a relapsed/refractory setting in recent landmark studies. Several phase 2 single-arm studies suggest that the addition of these agents in the frontline setting could further improve long-term disease control permitting one to reduce the exposure to cytotoxic drugs. However, a longer follow-up is needed. At the time of this writing, the only randomized phase 3 trial so far published is the ECHELON-1, which compares 1 to 1 BV-AVD (Bleomycin is replaced by BV) with standard ABVD in untreated advanced-stage III and IV HL. The ECHELON-1 trial has proven that BV-AVD is safe and more effective both in terms of long-term disease control and overall survival. Just recently, the results of the S1826 SWOG trial demonstrated that the combination nivolumab-AVD (N-AVD) is better than BV-AVD, while preliminary results of other randomized ongoing phase 3 trials incorporating anti-PD-1 in this setting will be soon available. The aim of this review is to present the recent data regarding these novel agents in first-line treatment of HL and to highlight current and future trends which will hopefully reshape the overall management of this disease.

Prognostic Impact of Serum β2-Microglobulin Levels in Hodgkin Lymphoma Treated with ABVD or Equivalent Regimens: A Comprehensive Analysis of 915 Patients

“…Unfortunately, there are no data regarding the correlation of sβ 2 m, neither with the circulating tumor DNA [71][72][73] and its changes during treatment nor with PET metrics, including baseline total metabolic tumor volume (TMTV) [74][75][76][77][78], total lesion glucolysis (TLG) [79,80] or lesion dissemination [81][82][83]. As sβ 2 m levels correlated strongly with almost all baseline features reflecting disease extent and aggressiveness in this study, it is reasonable to hypothesize a strong correlation with PET metrics, which, however, does not exclude the persistence of the independent prognostic significance of sβ 2 m.Finally, probably the main question to be asked in the near future is how sβ 2 m will affect the outcome of patients treated in the first line with chemotherapy plus novel agents such as BV-AVD or BreCADD, or-more importantly-how sβ 2 m will work as a prognostic factor under treatment with nivolumab-AVD [8].…”

“…The prognosis of Hodgkin lymphoma (HL) has dramatically changed over the last few decades, with the 5-year survival rate below 10% in the 1960s increasing to a 10-year survival rate exceeding 80% in the 2010s [1,2]. A further increase is expected with the use of novel immunotherapies for relapsed/refractory disease [3][4][5][6] or even their incorporation in earlier treatment lines [7,8]. The prognosis primarily depends on clinical stage as defined by the anatomic extent of the disease and the presence of B-symptoms according to the Ann Arbor staging system [9] and the Cotswolds [10] and Lugano modifications [11].…”

How I Follow Hodgkin Lymphoma in First Complete (Metabolic) Remission?

“…Despite the robust data, research in HL (phase II studies) treatment is changing with the incorporation of BV in early Hodgkin lymphoma, and checkpoint inhibitors in first-line treatment [90]. One of the largest studies on BV in early-stage, unfavorable HL was the BREACH study (n = 170) [91].…”

Doxorubicin Exposure and Breast Cancer Risk in Survivors of Adolescent and Adult Hodgkin Lymphoma

“…Our results are also relevant for treatment strategies for patients with newly diagnosed HL, when balancing the risks and benefits of systemic therapy and RT. Since effective novel agents (eg, antibody-drug conjugates and immune checkpoint inhibitors) have been introduced in the treatment for patients with HL, 48 future clinical trials should also aim at reducing the dose of doxorubicin. Further studies are needed to evaluate the effect of doxorubicin on BC risk in the absence of chest RT in more recently treated patient cohorts and to assess the role of genetic susceptibility in the development of doxorubicin-associated BC.…”