PF310 A SYSTEMATIC REVIEW OF THE CLINICAL EFFICACY OF TREATMENTS IN RELAPSED OR REFRACTORY DIFFUSE LARGE B‐CELL LYMPHOMA (R/R DLBCL)
Authors: Thuresson P.‐O. , Vander Velde N. , Harvey R. , Palvi G. , Qayum N. 
Published: June 2019

Background:

While the outcomes of patients with DLBCL have vastly improved in the past few decades, outcomes for patients with R/R DLBCL remain poor.

Aims:

The aim of this clinical systematic literature review (SLR) was to identify and summarise current clinical evidence around the pharmacological treatment options for patients with R/R DLBCL not eligible for stem‐cell transplant (SCT). A secondary objective was to assess the possibility of completing an indirect treatment comparison (ITC) or network meta‐analysis (NMA).

Methods:

Databases searched were: Embase®, MEDLINE®, The Cochrane Library (cut‐off date September 2018) and ASH 2018 abstracts (searched November 2018). Non‐English language articles were reviewed for inclusion on an individual basis. Only studies of patients with SCT‐ineligible R/R DLBCL were included in the analysis, per pre‐defined eligibility criteria. A network‐building exercise was conducted to identify whether a connected network of evidence could be constructed from identified studies. A post‐hoc network‐building exercise was conducted to re‐evaluate evidence not meeting the study criteria and explore a broader evidence base.

Results:

The SLR identified 36 studies of patients with R/R DLBCL (90 publications); of these, 19 studies (53 publications) met the eligibility criteria (treatments received are shown [Figure]). Six of the 19 studies were randomised controlled trials (RCTs [shown in Figure; lines connected to black circles]), and 13 studies were prospective, observational or single‐arm trials; a further three RCTs not meeting the eligibility criteria were identified (shown in Figure; lines connected to white circles). Thirteen of the 19 included studies had a sample size of <60. At baseline, median patient ages across the studies ranged from 54–74 years; three studies had >65% male patients; the proportion of patients with Ann‐Arbor stage III–IV disease ranged from 48%–90%. All studies reported objective and complete response rates; additional endpoints included progression‐free survival (PFS), overall survival (OS), safety, and discontinuation. The IWG 1999‐NHL guidelines were the most commonly used response criteria (10 studies). Eleven studies reported a median OS (estimates ranged between 5–22.2 months). Eleven studies reported median PFS (2.6–17.1 months). Response criteria and PFS definitions varied between studies, limiting cross‐study comparisons. It was not possible to construct a connected network of evidence either using data from RCTs or data from the broader post‐hoc study inclusion (Figure). Thus, conducting an NMA was deemed unfeasible.

Figure: Network‐building analysis of evidence in 9 RCTs

Treatments: BR = bendamustine, rituximab; DHAP = dexamethasone, cytarabine, cisplatin; ESHAP = etoposide, methylprednisolone, cytarabine, cisplatin; GDP = cisplatin, dexamethasone, gemcitabine; ICE = ifosfamide, etoposide, carboplatin; R = rituximab. Single‐arm studies not shown.

Lines connected to black circles: RCTs meeting the SLR criteria (SCT ineligible)

Lines connected to white circles: RCTs not meeting the SLR criteria

Summary/Conclusion:

This SLR provides a summary of the currently published evidence on treatments for patients with R/R DLBCL. Of the 36 studies of patients with R/R DLBCL, only nine (25%) were RCTs, preventing implementation of an ITC or NMA. These findings highlight the paucity of published RCTs to establish the comparative efficacy of treatments for R/R DLBCL. They also reveal the fragmented treatment landscape in R/R DLBCL, and demonstrate a lack of standard of care in this setting.

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