Background: Despite therapeutic advances in classical Hodgkin lymphoma (cHL), only half of patients with relapsed/refractory (R/R) cHL are cured with salvage chemotherapy followed by stem cell transplantation (SCT). Most studies to date have been undertaken in Europe or North America and data on treatment patterns and clinical outcomes from other regions are limited. We present the results from the B-CD30+ HOdgkin Lymphoma International Multi-center Retrospective Study of Treatment PractIces and OutComes (B-HOLISTIC), which assessed cHL treatment pathways, clinical outcomes and healthcare resource utilization across East Asia, Latin America, Middle East, South Africa, Australia and Russia (data as of 04 March 2020).
Methods: Data were collected retrospectively for patients (≥18 years) diagnosed with stage IIB-IV cHL or R/R cHL between 01 January 2010 and 31 December 2013, until death or last follow-up (whichever occurred first) across 13 countries. Patients with initial diagnosis of cHL and subsequent progression to R/R cHL were included in both groups, provided R/R cHL was diagnosed within the study period. The primary endpoint was progression-free survival (PFS) in patients with R/R cHL. Secondary endpoints included overall survival (OS), best clinical response, and adverse events (AEs).
Results: In total, 1703 patients were enrolled from East Asia (n=426), Latin America (n=366), Middle East and South Africa (n=694), Australia (n=56) and Russia (n=161): 1598 and 426 patients were eligible for the cHL and R/R cHL groups (321 patients in the cHL group progressed to R/R cHL and were included in both groups). Median study follow-up was 65.2 and 53.2 months for the cHL and R/R cHL groups. Baseline patient characteristics are shown in Table 1. All patients in the cHL group received first-line chemotherapy: the most common regimens were ABVD (1363/1598; 85.3%) and BEACOPP (104/1598; 6.5%). First-line radiotherapy was given to 357/1598 (22.3%) patients in the cHL group. For R/R cHL, intensive chemotherapy was used as first-line salvage in 372/426 (87.3%) patients: the most common regimens were ESHAP (98/372; 26.3%) and DHAP (65/372; 17.5%), with an overall response rate of 62.0% (complete remission in 30.8% and partial remission in 31.2%). Of the 426 patients with R/R cHL, 292 (68.5%) were eligible for SCT at relapse/refractory diagnosis; 10 patients who were initially ineligible for SCT subsequently became eligible. In total, 222/302 (73.5%) eligible patients underwent SCT; 63/222 (28.4%) patients relapsed after SCT. Median PFS (95% CI) for the R/R cHL group was 13.2 (9.9-20.2) months following initial therapy (Figure 1), with estimated 1-, 3- and 5-year PFS rates of 51.2%, 38.7%, and 33.9%, respectively (Table 2). Median PFS was not reached for the first-line cHL group. Factors for PFS in the R/R cHL group are shown in Table 3. Median OS was not reached for both groups. All-cause, any grade AEs were reported by 783/1598 (49.0%) patients with cHL and by 233/426 (54.7%) patients with R/R cHL. Serious AEs were reported by 303/1598 (19.0%) patients with cHL and by 103/426 (24.2%) patients with R/R cHL: the most common (≥2.0%) were febrile neutropenia, pneumonia and pyrexia for cHL, and febrile neutropenia and pyrexia for R/R cHL.
Conclusion: Results from B-HOLISTIC show that PFS rates remain low in patients with R/R cHL receiving salvage therapy; the greatest risk was among patients with inadequate response to salvage chemotherapy. The low PFS rates highlight the importance of considering novel targeted therapies to address unmet medical needs. PFS rates in patients with cHL were comparable with previous studies from Italy, Spain, and Israel (Avigdor A et al. EHA 2020) and the ECHELON-1 study (Bartlett NL et al. ASH 2019). The higher OS rates compared to PFS rates may be related to the effect of modern salvage regimens. Approximately half of patients with R/R cHL underwent SCT which may support the use of targeted therapies. Overall, these results from 2010-2013 show that despite the differences in healthcare systems, ethnicities and treatment patterns in B-HOLISTIC, clinical outcomes remain consistent. The authors note that given that the management of high-risk cHL has changed dramatically since 2013, further investigation in diagnostic criteria, response assessment and treatment patterns is needed.
Study support: Data analysis (IQVIA) and medical writing (Synergy Vision) funded by Takeda Pharmaceuticals.
Ferhanoglu:Takeda: Other: Advisory Board; Abbvie: Other: Advisory Board; Roche: Other: Advisory Board; Janssen: Other: Advisory Board. Kim:Novartis: Consultancy; AstraZeneca and Korea Health Industry Development Institute: Research Funding; Sanofi: Consultancy; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy; Voronoi: Consultancy; Boryung: Consultancy; AstraZeneca: Consultancy; Takeda: Consultancy. Karduss:Takeda: Honoraria. Rivas-Vera:Takeda: Current Employment, Other: Steering Committee in Clinical Research; Roche: Consultancy. Lim:National Cancer Centre Singapore: Current Employment. Yeh:AbbVie: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Astex: Membership on an entity's Board of Directors or advisory committees. Abdillah:Takeda: Current Employment. Huang:Takeda: Current Employment. Dalal:Takeda: Current Employment, Current equity holder in publicly-traded company. Wan:Takeda: Current Employment. Hertzberg:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support of parent study and funding of editorial support; Gilead: Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; BMS: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.
