Connors, Joseph M

Abstract Approximately one‐third of patients diagnosed with Hodgkin lymphoma presenting with Stage IV disease do not survive past 5 years. We present updated efficacy and safety analyses in high‐risk patient subgroups, defined by Stage IV disease or International Prognostic Score (IPS) of 4–7, enrolled in the ECHELON‐1 study that compared brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as first‐line therapy after a median follow‐up of 37.1 months. Among patients treated with A + AVD ( n = 664) or ABVD ( n = 670), 64% had Stage IV disease and 26% had an IPS of 4–7. Patients with Stage IV disease treated with A + AVD showed consistent improvements in PFS at 3 years as assessed by investigator (hazard ratio [HR], 0.723; 95% confidence interval [CI], 0.537–0.973; p = 0.032). Similar improvements were seen in the subgroup of patients with IPS of 4–7 (HR, 0.588; 95% CI, 0.386–0.894; p = 0.012). The most common adverse events (AEs) in A + AVD‐treated versus ABVD‐treated patients with Stage IV disease were peripheral neuropathy (67% vs. 40%) and neutropenia (71% vs. 55%); in patients with IPS of 4–7, the most common AEs were peripheral neuropathy (69% vs. 45%), neutropenia (66% vs. 55%), and febrile neutropenia (23% vs. 9%), respectively. Patients in high‐risk subgroups did not experience greater AE incidence or severity than patients in the total population. This updated analysis of ECHELON‐1 shows a favorable benefit‐risk balance in high‐risk patients.

Abstract Purpose: To evaluate safety and efficacy outcomes for subjects on the ECHELON-1 study treated in North America (NA). Patients and Methods: ECHELON-1 is a global, open-label, randomized phase III study comparing doxorubicin, vinblastine, and dacarbazine in combination with brentuximab vedotin (A+AVD) versus ABVD (AVD + bleomycin) as first-line therapy in subjects with stage III or IV classical Hodgkin lymphoma (cHL; NCT01712490). Subjects were randomized 1:1 to receive A+AVD or ABVD intravenously on days 1 and 15 of each 28-day cycle for up to 6 cycles. Results: The NA subgroup consisted of 497 subjects in the A+AVD (n = 250) and ABVD (n = 247) arms. Similar to the primary analysis based on the intent-to-treat population, the primary endpoint [modified progression-free survival (PFS) per independent review] demonstrated an improvement among subjects who received A+AVD compared with ABVD (HR = 0.60; P = 0.012). For PFS, the risk of progression or death was also reduced (HR = 0.50; P = 0.002). Subsequent anticancer therapies were lower in the A+AVD arm. Grade 3 or 4 adverse events (AEs) were more common, but there were fewer study discontinuations due to AEs in the A+AVD arm as compared with ABVD. Noted differences between arms included higher rates of febrile neutropenia (20% vs. 9%) and peripheral neuropathy (80% vs. 56%), but lower rates of pulmonary toxicity (3% vs. 10%) in subjects treated with A+AVD versus ABVD. Conclusions: The efficacy benefit and manageable toxicity profile observed in the NA subgroup of ECHELON-1 support A+AVD as a frontline treatment option for patients with stage III or IV cHL.

Key PointsA new molecular assay identifies conventional and leukemic nonnodal MCL with differing clinicobiological features. The integration of the novel assay with genetic alterations identifies subsets of MCL patients with different management and outcome.