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.

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

Figure 1

Study design and response rates of Phase II CheckMate 205 Study (cohort D). cHL = classical Hodgkin lymphoma; ECOG: Eastern Cooperative Oncology Group; FU/obs = follow-up/observation, Q2W = once every two weeks, N+AVD = nivolumab, doxorubicin, vinblastine, dacarbazine, CR = complete responses; ORR = overall response rate (numbers in parentheses refer to rates per investigator). It should be noted that response assessments were made by using 2007 International Working Group criteria [75] and not the revised criteria of Lugano [76].

Figure 2

Study design and response rates of NIVAHL. cHL = classical Hodgkin lymphoma; ECOG: Eastern Cooperative Oncology Group; Nivo = nivolumab, AVD = doxorubicin, vinblastine, dacarbazine, EoT = end of treatment, CMR = complete metabolic response; ISRT = involved-site radiation therapy, 3y PFS = 3-year progression-free survival.

Figure 3

Treatment schedule and response rates of sequential administration of pembrolizumab–AVD. cHL = classical Hodgkin lymphoma; ECOG: Eastern Cooperative Oncology Group; AVD = doxorubicin, vinblastine, dacarbazine, CMR = complete metabolic response; FU/obs = follow-up/observation, 3y PFS = 3-year progression-free survival; 3y OS = 3-year overall survival, *, depending on patient stage and disease bulk.

Figure 4

Treatment schedule and response rates of concomitant administration of pembrolizumab–AVD. cHL = classical Hodgkin lymphoma; ECOG: Eastern Cooperative Oncology Group; AVD + P = pembrolizumab, doxorubicin, vinblastine, dacarbazine, CMR = complete metabolic response; FU/obs = follow-up/observation, 2y PFS = 2-year progression-free survival; 2y OS = 2-year overall survival.