R-EPOCH May Be Viable Option for Patients with High-Risk DLBCL

Results from a single-center study show that the drug combination R-EPOCH leads to a high overall response rate (ORR) in patients with high-risk diffuse large B-cell lymphoma (DLBCL). Researchers also found that rates of complete response (CR) were higher among patients who received dose-adjusted R-EPOCH.

Up to 40 percent of patients with DLBCL who receive standard R-CHOP will relapse following treatment, lead author Vishwanath Sathyanarayanan, MD, from the University of Texas MD Anderson Cancer Center, explained. Earlier clinical trials have shown that R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) improves outcomes in patients with DLBCL, and the combination is being compared with R-CHOP in an ongoing phase III clinical trial.

Dr. Sathyanarayanan and colleagues conducted a retrospective review of patients treated with R-EPOCH at MD Anderson Cancer Center between 2010 and 2014. Results from this real-world population were presented at the 2016 ASH Meeting on Lymphoma Biology.

“This is one of the largest retrospective studies to assess the response to R-EPOCH in patients with newly diagnosed DLBCL with dose-adjusted chemotherapy,” Dr. Sathyanarayanan told ASH Clinical News. “R-EPOCH is a highly effective regimen in patients with high-risk DLBCL, and it may allow us to reach a higher cure rate than with R-CHOP alone, though further studies are needed.”

Researchers analyzed demographic, prognostic, and treatment variables, compared with clinical response and survival outcomes in 205 patients (median age = 59 years; range = 22-86 years). Patients with secondary central nervous system or double-hit lymphoma were excluded from this analysis.

Many of the patients were considered high-risk: 48 percent of patients had an International Prognostic Index (IPI) score of 3-5, 30 percent had non-germinal center subtype (non-GCB), and 75 percent had Ki-67 expression ≥80 percent.

In contrast with earlier data, survival was similar regardless of specific risk factors, which suggests that R-EPOCH may help negate poor prognosis, according to Dr. Sathyanarayanan. “In previous studies, the benefit was mainly evident in the germinal center sub-type due to suppression of BCL-6 by infusional etoposide,” he said. “We found GCB and non-GCB subgroups had similar outcomes.”

This analysis excluded patients with double-hit lymphomas, but he noted that the benefits of R-EPOCH are similar between patients with and without double-protein-expression lymphoma.

The authors reported an ORR of 95.5 percent, with 89.6 percent of patients achieving a CR.

Patients fared significantly better when R-EPOCH was dose-adjusted based on their absolute neutrophil count (ANC) nadir (if the nadir ANC >500/uL, doses of etoposide, doxorubicin, and cyclophosphamide for the next cycle are all increased by 20%), with 94 percent of dose-adjusted patients achieving a CR compared with 83 percent of those whose regimen was not adjusted (p value not reported).

At a median follow up of 2.8 years, the median overall survival (OS) and progression-free survival (PFS) had not yet been reached, even among patients with IPI scores 3-5 (TABLE).

Again, more patients who received dose-adjusted R-EPOCH were alive at three years, compared with an unadjusted regimen: 92 percent versus 80 percent (p value not reported).

The treatment was “relatively well tolerated,” according to the authors. Forty-seven patients (23%) were admitted for neutropenic fever, which, they noted, is in line with earlier studies.

Authors caution that this is a single-center, retrospective study, noting that data from the randomized, phase III trial of R-CHOP versus R-EPOCH expected later this year will help shed more light on their findings.


Reference

Sathyanarayanan V, Issa AK, Ahmed MA, et al. DA-EPOCH-R for high risk diffuse large B-cell lymphoma (DLBCL): The University of Texas MD Anderson Experience. Abstract #88556. Presented at the 2016 ASH Meeting on Lymphoma Biology, June 20, 2016; Colorado Springs, CO.

TABLE. Response and Survival Rates Based on High-Risk Features
Variable Overall Response Rate, n (%) 3-Year Overall Survival (95% CI) p Value for ORR/OS
International Prognostic Index score
1 62 (98) 0.98 (0.95-1) 0.4/0.01
2 42 (96) 0.85 (0.75-0.97)
3-5 90 (94) 0.8 (0.72-0.89)
Cell of origin
Germinal center subtype 97 (94) 0.87 (0.8-0.94) 0.7/0.3
Non-germinal center subtype 59 (97) 0.9 (0.83-0.99)
Ki67 expression ≥80%
No 43 (98) 0.8 (0.7-0.95) 0.7/0.3
Yes 126 (95) 0.89 (0.84-0.95)
CD 5- 115 (97) 0.87 (0.81-0.94) 0.26/0.73
CD5+ 23 (91) 0.87 (0.74-1)
CD 30- 67(91) 0.84 (0.75-0.94) 0.66/0.85
CD 30+ 28(97) 0.81 ( 0.67- 0.98 )
MYC+/BCL 2- 10 (100) 1 (1-1) 1.00/0.51
MYC-/BCL2+ 13 (92.3) 0.85 (0.67-1) 1.0/0.51
Adjusted Dosing
No 49 (93) 0.8 (0.69-0.92) 0.03/NA
Yes 120 (99) 0.92 (0.87-0.98)

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