SAN DIEGO Researchers have identified an ultra-high risk category of patients with diffuse large B-cell lymphoma (DLBCL) who have dismal outcomes on existing therapies and should therefore receive high priority for development of new drugs and cellular therapies.1

“There is a high potential for cure in DLBCL patients with later relapses, while outcome in patients with primary treatment failure is less clear,” said Kami J. Maddocks, MD, division of hematology, department of internal medicine, The Ohio State University, Columbus. “Pre-rituximab data indicated poor prognosis in patients with primary progression or early relapse.”

To describe outcomes and identify prognostic factors associated with poor outcomes among patients with DLBCL who experience primary treatment failure, investigators retrospectively analyzed data from 331 patients with DLBCL in the registry of diffuse large B-cell lymphoma with primary treatment failure (REFINE) study. Patients were diagnosed between 2008 and 2015 and had received upfront chemoimmunotherapy including an anthracycline and a CD20-directed antibody.

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Patients had also developed 1 of 3 patterns of primary treatment failure: relapse fewer than 6 months following complete remission (early relapse), partial remission or stable disease with upfront therapy (residual disease), or progressive disease while receiving upfront therapy (primary progression).

Two-year overall survival from time of primary treatment failure was 45.5% (95% CI, 34.5-56.5) for early relapse, 30.6% (95% CI, 20.0-41.2) for residual disease, and 18.5% (95% CI, 11.4-25.6) for primary progression (P < .001).

Researchers also found that 2-year overall for NCCN-IPI intermediate-high/high risk patients was 10.9% (95% CI, 4.0-17.8) compared with 42.3% (95% CI, 31.3-53.3) for intermediate-low risk patients and 57.4% (95% CI, 39.8-75.0) for low risk patients (P < .001).

Among patients with germinal center B-cell tumors, those with c-MYC mutation-positive tumors had a 2-year survival of only 11.0% (95% CI, 0.0-21.6) vs 34.9% (95% CI, 19.4-50.4) for c-MYC mutation-negative tumors (P = .002) and 42.3% (95% CI, 30.9-53.7) for non-germinal center tumors (P = .01).

After adjusting for multiple variables, researchers found that c-MYC mutation positivity and NCCN-IPI at the time of primary treatment failure were independently predictive of overall survival.

For the 144 patients with primary progression, NCCN-IPI intermediate-high/high risk, or c-MYC mutation positivity who had complete information on all 3 factors, 2-year overall survival was 13.6% (95% CI, 5.8-21.4), representing an ultra-high risk category. In contrast, patients without ultra-high risk features had a 2-year overall survival of 57.6% (95% CI, 40.6-74.7; P < .001).

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The findings suggest that patients identified with primary treatment failure and ultra-high risk features should be prioritized to clinical trials including novel agents and cellular therapies.

Dr Maddocks concluded that this study “provides a benchmark for future trials with novel therapies in this high-risk population of patients.”


  1. Maddocks KJ, Epperla N, Chavez JC, et al. Diffuse large B-cell lymphoma with primary treatment failure: Identification of ultra-high risk patients and benchmarking for experimental therapies. Paper presented at: American Society of Hematology (ASH) 58th Annual Meeting and Exposition; December 3-6, 2016; San Diego, CA.