The researchers also found, however, that “MHG and BL share high expression of signatures that contain cell-cycle genes, ribosome biogenesis, MYC overexpression, and TCF3 targets, which suggests a shared proliferative phenotype.”
The team determined that MHG has “a highly proliferative phenotype and shares features with centroblasts of the germinal center dark zone.”
Another discovery was that MHG patients in the REMoDL-B trial had worse progression-free survival (PFS) than their peers.
Among patients who received R-CHOP, the estimated 3-year PFS was:
- 37% for MHG patients
- 78% for patients with GCB DLBCL
- 64% for patients with activated B-cell like (ABC) DLBCL
- 65% for patients with unclassified DLBCL.
Among patients who received bortezomib plus R-CHOP, there was a trend toward improved PFS for patients with MHG DLBCL (58%; P = .08).
Validation cohort
Dr. Sha and colleagues validated their initial findings using RNA sequencing data from another group of DLBCL patients (Cell. 2017 Oct 5;171[2]:481-94.e15). This data set included 624 patients who received rituximab-based therapy.
Seventy-two patients in this group had MHG DLBCL (11.5%), and most MHG patients had GCB DLBCL (82%).
The researchers said the MHG group in this cohort “showed similar associations with clinical variables” and a “similar mutation spectrum” as the MHG group in the REMoDL-B cohort. Additionally, MHG patients in the validation cohort had inferior overall survival (P less than .001) compared to patients with non-MHG GCB DLBCL.
Dr. Sha and colleagues said the poor prognosis in MHG patients in both cohorts suggests a need for different treatment approaches in this group.
In the related editorial, Wing C. Chan, MD, of City of Hope Medical Center in Duarte, Calif., echoed that sentiment and said it will be important to include patients with high-risk DLBCL in clinical trials.
“Their tumors should be comprehensively characterize[d] for correlative analysis to determine the molecular lesions that underlie their biology and response to treatment,” Dr. Chan wrote.
Dr. Chan disclosed a patent for a diagnostic algorithm on GCB/ABC-type DLBCL and a patent on a diagnostic algorithm for peripheral T-cell lymphoma.
Dr. Sha and colleagues disclosed relationships with a range of pharmaceutical companies. The team’s research was supported by a grant from Bloodwise.
The REMoDL-B trial was endorsed by Cancer Research UK and was funded by Janssen-Cillag.
SOURCES: Sha C et al. J Clin Oncol. 2019 Jan 20;37(3):202-12. doi: 10.1200/JCO.18.01314; Chan WC. J Clin Oncol. 2019 Jan 20;37(3):175-7. doi: 10.1200/JCO.18.01910; Ennishi D et al. J Clin Oncol. 2019 Jan 20;37(3):190-201. doi: 10.1200/JCO.18.01583