Time to Progression a Key Prognostic Indicator in R/R DLBCL

Time-to-progression (TTP) following frontline R-CHOP is a “robust” predictor of prognosis in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), according to a new report.

The findings are significant because they are based on real-world data and because they suggest an easy-to-use method of prognostic prediction. The study was published in Therapeutic Advances in Medical Oncology.¹

About two-thirds of patients with DLBCL can be cured with anthracycline-based chemoimmunotherapy, such as rituximab (Rituxan; Genentech and Biogen) plus cyclophosphamide, doxorubicin, vincristine, and prednisone, the regimen commonly known as R-CHOP, the authors explained.

“Nevertheless, approximately 30-40% of patients experience primary refractoriness to the initial R-CHOP therapy or have a relapse event after achieving a complete response (CR),” they wrote. Subsequent treatments tend to be ineffective, they added.²

The typical second-line therapy has been platinum-based salvage chemotherapy followed by consolidative autologous stem cell transplantation (ASCT) in patients who demonstrate a response. Yet, the authors noted that many patients are ineligible for ASCT, and many who undergo the procedure will still experience a relapse. Novel therapies like anti-CD19 chimeric antigen receptor (CAR) T-cell therapies and monoclonal antibodies have shown the potential to cure certain patients. However, many such therapies are costly and logistically challenging, the authors noted, creating a significant need to better understand which patients are most likely to benefit from such advanced therapies.

The investigators decided to look at real-world data to clarify which patients are most likely to survive and benefit from further therapy following R-CHOP.

They identified 231 patients with R/R DLBCL who were treated at a tertiary medical center, of whom 88 (38.1%) were primarily refractory to R-CHOP and 143 (61.9%) experienced recurrence. When the authors stratified patients based on TTP, they found that the 2-year overall survival (OS) rate was 35.4% in patients with TTPs of less than 12 months but 74.4% among patients with TTPs longer than 24 months. Patients in the short TTP group also had lower response rates to second-line therapies and were less likely to undergo ASCT. A multivariate analysis showed TTP was an independent prognostic factor for both OS and progression-free survival (PFS).

The investigators also constructed a population-based validation cohort using Taiwan’s National Health Insurance Research Database. The population-based cohort had 723 patients with R/R DLBCL and affirmed the initial findings.

The findings align with previous research into the impact of TTP on patient outcomes, which they said consistently shows that there is a strong association between the timing of relapse or refractoriness and long-term survival outcomes.

“Our study found that, aside from being linked to poor survival outcomes, a short TTP is significantly associated with lower response rates to second-line treatment and a decreased likelihood of proceeding to ASCT,” they wrote.

They said this highlights the “urgent need” for more innovative treatments for these patients.

In addition to TTP, the investigators said their multivariate analysis showed that bulky lesions at the time of R/R disease, low serum albumin before salvage therapy, and high International Prognostic Index scores were linked with poor OS. Male gender and low hemoglobin prior to salvage therapy were associated with poor PFS, they said.

The investigators said the primary limitation of their study is its retrospective nature, which they said resulted in some missing data. Still, they said, their validation cohort shows They said further studies with systematic cutoff validation would strengthen the robustness of prognostic stratification.

References

1. Cheng CL, Huang TC, Tuan YH, et al. Time to progression is a simple and robust prognostic factor for survival in relapsed or refractory diffuse large B-cell lymphoma. Ther Adv Med Oncol. 2025;17:17588359251396884. Published 2025 Dec 4. doi:10.1177/17588359251396884

2. Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(27):4184-4190. doi:10.1200/JCO.2010.28.1618