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MYC rearrangement may influence OS, treatment efficacy for DLBCL
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Rearrangement of the oncogene MYC served as a negative prognostic factor for patients with diffuse large B-cell lymphoma, or DLBCL, treated with immunochemotherapy, according to the results of a prospective randomized trial.
“According to published series, MYC rearrangement (MYC-R) is observed in 7% to 21% of DLBCL,” Christiane Copie-Bergman, MD, PhD, professor of medicine at Université Paris-Est, and colleagues wrote. “In DLBCL, most studies have reported MYC-R as a strong adverse prognostic factor, whereas others failed to demonstrate any significant impact of MYC-R alone on survival.”
Copie-Bergman and colleagues sought to determine the prognostic value of MYC translocation partner genes in patients with DLBCL who harbored MYC-R. They examined data from 774 patients enrolled in the GELA/LYSA clinical trials treated with first-line rituximab (Rituxan; Genentech, Biogen Idec) and anthracycline-based chemotherapy.
Using fluorescence in situ hybridization, the researchers observed MYC-R in 8.9% of patients (n = 51).
Seventy-four percent (n = 37) of patients with MYC-R had the germinal center B-cell–like subtype with no distinctive morphological and phenotypic features. Further, 19 patients had MYC single-hit (MYC-SH) and 32 patients have MYC double-hit (MYC-DH) DLBCL.
The MYC translocation partner was an immunoglobulin gene (MYC-IG) in 24 patients and a non-immunoglobulin gene (MYC-non-IG) in 26 patients. When compared with MYC negative patients, patients with MYC-IG had a reduced OS (P = .0002).
No significant survival difference occurred between patients with MYC-non-IG and MYC-negative patients.
In multivariate analyses, MYC-IG independently corresponded with poor PFS (P = .0051) and OS (P = .0006). Because MYC-IG patients tended to be older than MYC-non-IG patients (median age, 69 years vs. 60.5 years; P = .027), age served as an independent prognostic factor.
“In conclusion, our study shows that patients with MYC-IG rearrangements are negative predictors of survival in patients with DLBCL in the setting of prospective controlled clinical trials,” Copie-Bergman and colleagues wrote. “We also show that MYC-R predicted a worse prognosis with no interaction with treatment arm and chemotherapy regimen, suggesting that conventional chemotherapy … regimens are not the optimal approaches for these patients. Potential targeted therapy acting on MYC oncogenesis pathway should be investigated.” – by Cameron Kelsall
Disclosure: Copie-Bergman reports travel expenses from and an advisory role with Celgene. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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