Real-World Characteristics of Patients with Classical Hodgkin Lymphoma Receiving Frontline Brentuximab Vedotin with Chemotherapy: A Retrospective Analysis with Propensity Score Matching

Introduction: In the phase 3 ECHELON-1 study (NCT01712490), treatment with brentuximab vedotin, doxorubicin, vinblastine and dacarbazine (A+AVD) significantly improved modified progression-free survival in patients with newly-diagnosed stage III or IV classical Hodgkin lymphoma (cHL) compared with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). The results of ECHELON-1 supported the March 2018 US FDA approval of A+AVD for adults with frontline (FL) stage III or IV cHL. To optimize outcomes for patients with stage III or IV cHL receiving ABVD, the current National Comprehensive Cancer Network guidelines recommend an interim PET/CT imaging (PET2) at the end of cycle 2 to inform escalation or de-escalation of therapy. In the current study we describe the real-world patient characteristics, supportive care use, and PET2 utilization in A+AVD and ABVD patients outside of the clinical trial setting in the US.

Methods: Using medical and pharmacy claims data in the US Symphony Health Solutions database, a retrospective cohort analysis of patients with cHL receiving FL A+AVD or ABVD was conducted to compare treatment and utilization characteristics. Patients ≥18 years with one inpatient or two outpatient ICD-9 or 10 cHL diagnosis codes, newly prescribed A+AVD or ABVD (index date) between March 2018 and January 2020, and with ≥6 months continuous activity before and a minimum of 3 months after the index date were included. To adjust for confounding factors, a 1:1 propensity score matching analysis was performed based on age, gender, baseline comorbidities, geographic region and length of follow-up.

Results: A total of 4259 patients met inclusion criteria (1002 A+AVD and 3257 ABVD) with a median follow-up duration of 14 and 15 months, respectively. In unmatched cohorts, median age at index date of A+AVD vs ABVD was 48 and 39 years, with 41% and 52% of patients between the ages of 18-39, and 34% vs 20% age ≥60, respectively. Patients on A+AVD had higher comorbidity burden across all conditions included in the Charlson Comorbidity Index, with 41% vs 33% of ABVD patients reporting 1+ comorbidities, with chronic pulmonary disease (18% vs 14%, p=0.006) being the most prevalent (Table 1). Following propensity score matching, A+AVD patients received significantly higher granulocyte-colony stimulating factor (G-CSF), 90% vs 44%, with 80% and 20% as primary prophylaxis (p<0.001) vs ABVD, respectively. In the A+AVD and ABVD cohorts, only 31% and 38% of patients underwent interim PET2 restaging, respectively (Table 2). In ABVD patients, 44% who received an interim PET2 and 33% who did not receive an interim PET2 de-escalated to AVD. The rate of subsequent therapy was similar between A+AVD and ABVD (13% vs 11%; p=0.163); of the patients who received subsequent therapy, 43% of ABVD patients received a brentuximab vedotin-containing regimen and 19% of A+AVD were retreated with a brentuximab vedotin-containing regimen.

Conclusions: In this first real-world evaluation, patients with cHL receiving FL A+AVD were older, had higher burden of comorbidities, utilized recommended G-CSF as primary prophylaxis, and had similar rate of subsequent therapy compared to ECHELON-1 patients. Only about one third of patients underwent interim PET2 restaging, and less than half of the patients who started on ABVD were de-escalated to AVD. Confounding by unmeasured characteristics, such as disease stage and PET/CT results, is a limitation of this and any retrospective study based on claims data. However, this hypothesis-generating analysis suggests the need to: 1) control for patient characteristics (e.g., age, comorbidities) in comparative real-world analyses; 2) understand reasons for the lack of PET/CT use; and 3) evaluate the actual use of the interim PET2 to escalate or de-escalate treatment in patients with cHL. The need to optimize treatment outcomes while maximizing short- and long-term treatment efficacy and safety is paramount. Characteristics and management of this real-world population with cHL differed from those in the ECHELON-1 trial, demonstrating the importance of retrospective studies in assessing the impact of new regimens on clinical practice and in identifying areas for further education of practitioners.