UK real-world gene expression profiling for DLBCL

On 8 November, Dan Painter from the University of York, UK, and colleagues, published in the British Journal of Haematology findings from the UK’s population-based Haematological Malignancy Research Network (HMRN). According to the authors, this is the largest real-world gene expression profiling (GEP) for diffuse large B-cell lymphoma (DLBCL) to date.

DLBCL is the most common B-cell malignancy that presents with a wide range of clinical characteristics and prognostic factors, depending on the biological subgrouping of the disease. GEP of DLBCL is crucial for outcome analysis and treatment planning for patients in different molecular subgroups. The data collection for this report started in September 2004 and included follow-up of all newly-diagnosed DLBCL patients until death up to March 2018, across 14 HMRN hospitals in the UK.

Study design

• Study duration: 2004–2018
• N = 2197 newly-diagnosed DLBCL patients with de novo, not-otherwise specified (NOS) DLBCL
• Of those, n = 706 (32.1%) could be GEP analysed and classified by cell of origin (COO)
• A transcriptome classifier was then used to further subcategorize patients in molecular high-grade (MHG) class

Results

• Except for age, the demographics and clinical characteristics of the 706 patients used for GEP were similar to the whole cohort (N = 2197)
• In both groups (GEP/COO and whole cohort), approximately 89% of patients were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and 2–3% with cyclophosphamide, vincristine, doxorubicin, methotrexate (CODOX-M)
• Five-year overall survival (OS):
  • GEP/COO group: 66.8% vs whole cohort: 61.2% (P < 0.05)
• Relative survival:
  • GEP/COO group: 76.0% vs whole cohort: 71.1% (P < 0.05)
• Both OS and relative survival were significantly longer in the GEP/COO group when compared to the whole cohort
• Following the standard three-group classifier:
  • Germinal center B-cell (GCB): n = 384 (54.4%)
  • Activated B-cell (ABC): n = 194 (27.5%)
  • Unclassified: n = 128 (17.1%)
• Compared to the ABC group, patients in the GCB group were:
  • Significantly younger (median age, 70.5 years vs0 years; P < 0.05)
  • Had better OS (five-year OS, 53.7% vs9%)
  • Were more likely to have a MYC genetic rearrangement (5.5% vs1%)
• Separating patients with MHG from GCB led to the following five-year OS outcomes:
  • GCB group: 76.9%
  • ABC group: 54.4%
  • MHG group: 41.8%
  • Unclassified group: 68.3%
• The survival of patients in the MHG group was significantly worse than of those remaining in the GCB group (P < 0.001) and of those in the ABC group (P < 0.05)
• The cancer stage of MHG patients was more likely to be III-IV than of those in the GCB group (80.4% vs0%; P < 0.05)
• The OS curve of the MHG group looked very similar to that of Burkitt lymphoma patients
• MHG patients were more likely to have MYC rearrangement, when compared to the GCB group (P < 0.001)

The real-world findings of this study indicate that genetic profiling in DLBCL plays an important prognostic role and should be incorporated into routine diagnostic procedures. The authors further stated that MHG stratification from the conventional COO subgrouping might encourage the development of targeted trials for outcome improvement in this specific population.