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

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MDPI
DOI: 10.3390/ijms241713187

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Hodgkin lymphoma; novel agents; first-line treatment; brentuximab vedotin; nivolumab; pembrolizumab

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The long-term survival of HL patients is excellent with current standard of care, including combined-modality schedules and treatment intensity adaptation. However, a significant number of patients still experience primary refractory or relapse. Novel immunotherapeutic agents, such as BV and CPI, have shown outstanding efficacy in relapsed/refractory settings. Adding these agents in frontline treatment may further improve disease control and reduce the need for cytotoxic drugs. The results of ongoing phase 3 trials incorporating anti-PD-1 in this setting will provide more insights.
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.

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