A systematic literature review of the epidemiology, quality of life, and economic burden, including disease pathways and treatment patterns of relapsed/refractory classical Hodgkin lymphoma.

INTRODUCTION: A systematic literature review was conducted to understand disease burden in patients with relapsed/refractory classical Hodgkin lymphoma (R/R cHL). AREAS COVERED: Embase®, PubMed®, and Cochrane were searched for records from 2001 to 2020 in accordance with PRISMA guidelines. A total of 13,257 abstracts and 1731 papers were screened; 144 studies were identified. cHL accounted for 0.5% of all cancers, with 4‒66.7% of cases progressing to R/R disease (studies with >500 patients); this range varied across countries. Quality of life (QoL) was assessed via EORTC-QLQ-C30 (n = 7), EQ-5D (n = 5), SF-36 (n = 3), FACIT-F (n = 1), and MFI (n = 1) questionnaires. In general, pembrolizumab and other programmed cell death protein-1 inhibitors improved QoL scores. Brentuximab vedotin showed mixed outcomes, and high-dose therapy (HDT) and autologous stem-cell rescue (ASCR) showed worsening functionality/symptoms. Economic burden studies (n = 21) reported increased costs and health care resource in R/R cHL. Across clinical guidelines (n = 13) and treatment pattern studies (n = 46), HDT followed by ASCR was recommended as initial R/R cHL treatment. Pembrolizumab and nivolumab were frequently recommended for patients relapsing following HDT/ASCR. EXPERT OPINION: Despite recent treatment advances, patients with R/R cHL continue to report reduced quality of life. Unmet medical needs remain, particularly with respect to slowing disease progression and identifying the best treatment approaches for improving longer-term survival and quality of life. This systematic literature review provides an extensive overview of the current landscape in patients with R/R cHL, focusing on four key areas: epidemiology, QoL, economic burden, and disease management. These findings will be useful to those with an interest in managing patients with R/R cHL or in designing future studies.

Comparative Efficacy of Acalabrutinib in Frontline Treatment of Chronic Lymphocytic Leukemia: A Systematic Review and Network Meta-analysis.

PURPOSE: The goal of this study was to estimate the relative efficacy of acalabrutinib (monotherapy and in combination with obinutuzumab) compared with standard frontline treatments for chronic lymphocytic leukemia (CLL) in fludarabine-ineligible patients, through a network meta-analysis (NMA). METHODS: The efficacy of acalabrutinib from ELEVATE-TN (study of Obinutuzumab + Chlorambucil, Acalabrutinib [ACP-196] + Obinutuzumab, and Acalabrutinib in Subjects With Previously Untreated CLL) was compared to bendamustine + rituximab, chlorambucil-based therapy, alemtuzumab, ibrutinib mono/combination therapy and venetoclax + obinutuzumab using data from eight randomized controlled trials (RCTs). Relevant RCTs were identified using a systematic literature review. Two evidence networks were constructed: Network A, composed solely of RCTs that met the inclusion criteria; and Network B, composed of 7 RCTs and a published cross-trial comparison of ibrutinib from RESONATE-2 and chlorambucil + obinutuzumab from iLLUMINATE. Bayesian NMAs were conducted on progression-free survival (PFS) and overall survival (OS) endpoints; results were reported by using hazard ratios (HRs) and 95% credible intervals (CrIs). HRs were considered significant if their CrIs did not cross 1. Treatments were ranked by using the surface under the cumulative ranking area (SUCRA) values. Expert opinion from 2 hematologists was sought to validate results. FINDINGS: Both networks showed a significant improvement in PFS for acalabrutinib + obinutuzumab over all comparators. Both networks also showed a significant improvement in PFS for acalabrutinib monotherapy versus most comparators, with a significant difference to ibrutinib monotherapy found in Network A but not Network B. Conversely, a significant difference in PFS was observed for acalabrutinib monotherapy versus venetoclax + obinutuzumab in Network B but not Network A. Although OS HRs all favored acalabrutinib, most were not significant and were characterized by wide CrIs, indicating a high level of uncertainty. Acalabrutinib + obinutuzumab ranked highest in terms of PFS improvement (SUCRA values, 98% and 100%) and OS improvement (SUCRA values, 92% and 94%), followed by acalabrutinib monotherapy (SUCRA values for PFS, 88% and 90%; OS, 83% and 87%) in Networks A and B, respectively. IMPLICATIONS: Acalabrutinib was associated with favorable PFS and OS compared with frontline CLL therapies and ranked highest in treatment efficacy over the other comparators. The NMA was limited by heterogeneity in patient baseline characteristics across trials, variable treatment regimens, and short study follow-up times. Despite these limitations, the NMA provides insights into the relative efficacy of acalabrutinib compared with frontline CLL therapies in the absence of head-to-head clinical trials.