R-CHOP-Like Therapy Retreatment Yields Durable Responses in Late-Relapsing Diffuse Large B-Cell Lymphoma

Key Clinical Summary: 

• Design/Population: A retrospective real-world study from the BC Cancer database evaluated 65 patients with de novo DLBCL who experienced late relapse (>2 years after diagnosis) and were retreated with curative-intent R-CHOP–based therapy.
• Key Outcomes: ORR was 72% with CR 57%; median time to progression was 45.1 months and 2-year PFS 45.8%. Median OS was 38.6 months with 2-year OS 54.3%. Patients relapsing >5 years had significantly better outcomes. Most deaths were lymphoma-related (75%).
• Clinical Relevance: R-CHOP retreatment can achieve durable remissions and potential cure in late-relapsing DLBCL, particularly beyond 5 years, offering a less intensive alternative to transplant or CAR T-cell therapy in selected patients.

A real-world analysis from the BC Cancer database demonstrated that patients with diffuse large B-cell lymphoma (DLBCL) experiencing late relapse may achieve meaningful responses and durable disease control with retreatment using R-CHOP-based regimens.

“It is postulated that a second course of R-CHOP-based therapy may offer a less toxic and less resource-intense option for late-relapsing DLBCL, while still offering curative potential,” stated Jean-Nicolas Champagne, MD, FRCPC, P Hôpital Sacré-Coeur de Montréal, Montreal, Canada, and coauthors. “However, this approach has not been previously evaluated.”

This retrospective study included 65 patients with de novo DLBCL who relapsed more than 2 years after initial diagnosis and were retreated with curative-intent R-CHOP-based therapy. The primary outcome was time to progression (TTP), secondary outcomes were overall response rate (ORR), complete response rate (CR), progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS).

At relapse, the median age was 77 years (range, 52 to 89), with most patients presenting with advanced disease (81% stage 3 or 4), high-risk features (78% International Prognostic Index 3–5), and poor performance status (52% ECOG 2 to 4). The median time from initial diagnosis to relapse was 7.4 years (range, 2.5 to 15.9), and patients received a median of 5 cycles of therapy at relapse (range, 1 to 6). 

The overall response rate was 72%, including a complete response rate of 57% and 15% of patients achieving a partial response. At a median follow-up of 31.4 months (range, 3.3 to 192.5), the median time to progression was 45.1 months (95% confidence interval [CI], 2.9 to 87.3) and the median 2-year time to progression was 53.7% (95% CI, 40.4 to 67). The median PFS was 16.1 months (95% CI, 0 to 35.1) with 2-year PFS at 45.8% (95% CI, 32.7 to 58.9). Median disease-specific survival was 59.2 months (95% CI, 26.9 to 91.5) with a 2-year DDS of 64.3% (95% CI, 52.0 to 76.6), and median OS was 38.6 months (95% CI, 10.1 to 67) with 2-year OS at 54.3% (95% CI, 41.2 to 67.4). 

At relapse, 6 patients received multiagent chemoimmunotherapy, 2 enrolled in clinical trials, and 1 underwent CAR T-cell therapy, while most were treated with less intensive approaches including single-agent chemotherapy (n=3), radiation (n=6), or supportive care (n=4) due to ineligibility for intensive treatment. During follow-up, 36 deaths occurred, with 75% attributed to lymphoma or treatment toxicity, while 9 deaths were due to unrelated causes. 

Notably, patients relapsing more than 5 years after diagnosis had significantly better outcomes, with a 2-year time to progression of 66% compared to 9% for those relapsing between 2 and 5 years (hazard ratio [HR]], 0.30; 95% CI, 0.14 to 0.64; P = 0.001).

Dr Champagne and coauthors concluded, “In conclusion, this study is, to our knowledge, the first to demonstrate that patients with late-relapsing DLBCL may be effectively treated with a second course of R-CHOP-like therapy.”

“R-CHOP-like therapy yields durable remissions in a high proportion of patients, especially in those relapsing >5 years after diagnosis, allowing many patients to avoid more intensive and costly secondary therapies,” they added. 

Source:

Champagne JN, Villa D, Gerrie AS, et al. Retreatment with R-CHOP–like therapy in patients with late relapse of diffuse large B-cell lymphoma. Blood Advances. Published online January 29, 2026. doi:10.1182/bloodadvances.2025017620