DEL and DHL as indicators of poor prognosis after ASCT

A. F. Herrera from the Dana-Farber Cancer Institute, Boston, USA, and colleagues recently published results from a retrospective, multicenter study of 117 patients with R/R DLBCL, looking at the prognostic effect of the DLBCL sub-types Double-Expressor Lymphoma (DEL) or Double-Hit Lymphoma (DHL) status on ASCT outcome. These results were published in the Journal of Clinical Oncology in October, 2016. DEL was defined as 40% of tumor cells or over containing MYC expression and 50% or over containing BCL-2 expression. Rearrangements of MYC and BCL-2 and/or BCL6 were the criteria for DHL.

Highlights:

• 44% of patients had DEL, 10% of patients had DHL
• 4-year post-ASCT PFS DEL vs non-DEL = 48% vs 59% (P=0.049), 4-year post-ASCT OS = 56% vs 67% (P=0.10)
• 4-year post-ASCT PFS DHL vs non-DHL = 28% vs 57% (P=0.013), 4-year post-ASCT OS = 25% vs 61% (P=0.002)
• Patients with both DHL and DEL had 4-year post-ASCT PFS = 0%
• DEL and DHL were associated with poor outcomes following ASCT and patients with both had even worse outcomes

In an accompanying editorial, Sonali M. Smith of the University of Chicago provided further context for this work in addition to discussing the study’s limitations. The first was that DLBCL DEL and DHL categories are not formally defined by the WHO. Secondly, the population studied was small due to the inclusion criteria used in that only patients with R/R DLBCL sensitive to chemotherapy undergoing ASCT were assessed. Sonali M. Smith concluded by stating that due to the limitations of retrospective studies, and the issues mentioned above, it is essential that further prospective studies need to be conducted.

Abstract:

Relapsed or Refractory Double-Expressor and Double-Hit Lymphomas Have Inferior Progression-Free Survival After Autologous Stem-Cell Transplantation

Purpose

Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL.

Methods

Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization (FISH) for MYC were performed. In cases with MYC rearrangement or copy gain, FISH for BCL2 and BCL6 was also performed.

Results

A total of 117 patients were included; 44%had DEL and 10%had DHL. DEL and DHL were associated with inferior progression-free survival (PFS), and DHL was associated with poorer overall survival (OS). The 4-year PFS in patients with DEL compared with those with non-DEL was 48% versus 59% (P = .049), and the 4-year OS was 56% versus 67% (P = .10); 4-year PFS in patients with DHL compared with those with non-DHL was 28% versus 57% (P =.013), and 4-year OS was 25%versus 61%(P = .002). The few patients with concurrent DEL and DHL had a poor outcome (4-year PFS,0%). In multivariable models, DEL and DHL were independently associated with inferior PFS, whereas DHL and partial response (v complete response) at transplant were associated with inferior OS.

Conclusion

DEL and DHL are both associated with inferior outcomes after ASCT in patients with rel/ref DLBCL. Although ASCT remains a potentially curative approach, these patients, particularly those with DHL, are a high-risk subset who should be targeted for investigational strategies other than standard ASCT.

References:

1. A. F. Herrera. et al. Relapsed or Refractory Double-Expressor and Double-Hit Lymphomas Have Inferior Progression-Free Survival After Autologous Stem-Cell Transplantation. Journal of Clinical Oncology. Oct 2016. doi:10.1200/JCO.2016.68.2740
2. S. M. Smith. Impact of Double-Hit and Double-Expressor Phenotypes in Relapsed Aggressive B-Cell Lymphomas Treated With Autologous Hematopoietic Stem Cell Transplantation. Journal of Clinical Oncology. Oct 2016. doi:10.1200/JCO.2016.70.0625.