Treatment Patterns and Outcomes in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma: Experience from a Single UK Centre
Authors: Radford John , White Ellie , Castro Felipe A. , Chaturvedi Anshuman , Spielewoy Nathalie , Gibb Adam , Surinach Andy , Linton Kim , Shang Aijing , Wenger Michael 
Published: November 2019

Introduction: First-line (1L) therapy for diffuse large B-cell lymphoma (DLBCL) can cure ~60% of patients (pts), but ~10-15% do not respond and 20-25% relapse. Salvage chemotherapy with autologous stem cell transplant (ASCT) is standard for 'fit' pts with relapsed or refractory (R/R) disease. However ~50% of pts are ineligible for transplant and most who undergo ASCT will relapse; for these pts options are extremely limited. Here we evaluated R/R DLBCL treatment patterns and outcomes for pts managed at a single UK center to create a detailed 'real-world' comparator for novel therapies.
Methods: A detailed retrospective analysis of medical records was undertaken for pts with DLBCL 2006-2017 and a R/R event 2011-2017. Additional eligibility criteria were: age ≥18 years; ≥1 prior anti-CD20 antibody-containing chemo-immunotherapy regimen; no history of high-grade transformation; and no lymphomatous CNS involvement. Pt characteristics, treatments, responses, and overall survival (OS) were reported by line (L) of therapy (2L, 3L, 4L+) in all pts and in refractory pts (defined as no response to or relapse within 6 months of last treatment).
Results: Of 2025 pts diagnosed with DLBCL 2006-2017, 89 fulfilled eligibility including a R/R event 2011-2017: 89, 63, and 41 received 2L, 3L, and 4L+ treatment. Median age at 2L was 66 years (range 58-72). 58.4% (n=52) were male and 64.0% (n=57) were stage III/IV; 49.4% (n=44) were ABC subtype and 29.2% (n=26) were GCB. Systemic 2L therapies (≥5% incidence) included R-DHAP (20.2%; n=18), R-GDP (20.2%; n=18), DHAP (10.1%; n=9), R-GCVP (7.9%; n=7), and gemcitabine (5.6%; n=5). In 2L, 23.6% (n=21) of pts underwent ASCT. With each line, regimens became more diverse, with increased use of experimental therapies. Overall response rate was 46.1% in 2L, 27.0% in 3L, and 9.8% in 4L+. In refractory pts, it was 34.8%, 21.2%, and 7.9% (Table). OS is shown in the Figure and Table; 2-year OS was 30.6% in all R/R pts and 20.5% in refractory pts. Median OS was reduced in pts with low ECOG performance status or high LDH. Two-year OS was 71.4% in transplanted pts (n=23) and 16.3% in non-transplanted pts.
Conclusions: Despite multiple treatment options, pts with R/R DLBCL have a very poor prognosis, highlighting the need for rapid introduction of more effective therapies. This can be facilitated by robust data such as these, which may be used for comparing outcomes of novel therapies with those expected at a given line of treatment in the 'real world', unrestricted by the requirements of a trial protocol. Results will be compared with those from the SCHOLAR-1 study (Crump et al. Blood 2017;130:1800-8) to provide greater clarity regarding R/R DLBCL treatment outcomes in the 'real world' setting.

Disclosures
Radford: Seattle Genetics: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; ADC Therapeutics: Consultancy, Research Funding; AstraZeneca: Equity Ownership, Research Funding; GSK: Equity Ownership; BMS: Consultancy, Honoraria. Castro:F. Hoffmann-La Roche Ltd: Employment. Chaturvedi:Christie Hospital NHS Trust: Employment. Spielewoy:F. Hoffmann-La Roche Ltd: Employment. Gibb:Takeda: Research Funding. Surinach:Genesis Research: Employment. Shang:F.Hoffmann-La Roche AG: Employment. Wenger:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership.

OffLabel Disclosure:
"Atezolizumab (atezo) is a programmed death-ligand 1 (PD-L1) blocking antibody. In the United States, atezo is approved for treatment of pts with locally advanced or metastatic urothelial carcinoma who are: not eligible for cisplatin-containing chemotherapy (chemo) and whose tumors express PDL-1, or are not eligible for any platinum-containing chemo regardless of PD L1 status; or have disease progression during or following any platinum-containing chemo, or within 12 months of neoadjuvant or adjuvant chemo. Atezo is also approved: in combination with bevacizumab, paclitaxel and carboplatin for first-line treatment of pts with metastatic non-squamous non-small-cell lung carcinoma (NSCLC) with no EGFR or ALK genomic tumor aberrations, and for pts with metastatic NSCLC who have disease progression during or following platinum-containing chemo; in combination with paclitaxel protein-bound for the treatment of adults with unresectable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1; and in combination with carboplatin and etoposide, for the first-line treatment of adults with extensive-stage small cell lung cancer. Atezo is not approved for treatment of pts with multiple myeloma."