Review Identifies Top Prognostic Factors in Third-Line or Later DLBCL

By comprehensively reviewing data on patients who have received at least 2 treatments for diffuse large B-cell lymphoma (DLBCL), researchers have identified factors prognostic of outcomes such as overall survival, progression-free survival, or response to treatment.¹

With their findings, explained the researchers, it is more clear which prognostic variables should be used for comparing clinical and real-world data for treatment for the most common type of non-Hodgkin lymphoma. The findings were published in European Journal of Hematology.

Overall, there were 36 factors identified as having a prognostic impact on at least 1 clinical outcome. | Image Credit: laszlo - stock.adobe.com

Identifying predictors of disease outcomes is a priority for DLBCL, as a significant proportion of patients become refractory to or relapse after first-line chemo-immunotherapy treatment, and outcomes continue to be poor with subsequent treatment. Newer treatments like chimeric antigen receptor T-cell therapy have created a new standard in DLBCL treatment, though many patients still experience relapse after treatment.

As with other cancer types with high unmet needs, single-arm trials are often used to assess new potential treatments, enabling more timely availability of effective treatment. However, innate limitations accompany single-arm trials, including lack of comparative data and time-to-event endpoints.² To help bring contextualization to findings, external controls have been leveraged, including for trials of axicabtagene ciloleucel (Yescarta; Kite Pharma) and tafasitamab (Monjuvi; Incyte).

“The use of single-arm trials has allowed transformative therapies to be made more expeditiously available to patients with diseases that have high unmet needs. However, contextualizing the findings of these trials using external controls requires the identification of prognostic factors and pre-specification of variables for confounder adjustment,” wrote the researchers, noting inconsistent findings on the use of prognostic factors throughout trials.

An exploration of current data in third-line or later disease identified 46 studies published between 2016 and 2021, revealing various patient-, disease-, and treatment-related characteristics that impacted response to treatment. Following the review, an independent group of experts reviewed and ranked these characteristics through questionnaires, interviews, and quantitative ranking.

The top 5 factors identified mostly related to treatment experience, with the top-ranked variable being early failure on chemo-immunotherapy treatment. Other top-ranked factors included Eastern Cooperative Oncology Group performance status, being refractory to the last line of treatment, number of prior treatments, and double- or triple-hit lymphoma.

“The use of a clinical expert review involving a questionnaire followed by individual interviews provides several advantages, particularly in its mixed methods research design that combines both quantitative and qualitative approaches,” wrote the researchers. “By doing so, the responses can be consolidated while still offering an in-depth understanding of the clinical experts' perspectives.”

Other factors included in the top 10 included age at the start of treatment, International Prognostic Index risk classification, Ann Arbor disease stage, serum lactate dehydrogenase, and Deauville score.

Overall, there were 36 factors identified as having a prognostic impact on at least 1 clinical outcome. The researchers found no statistically significant effect measure modifiers (EMMs) across the studies.

Throughout the review, the researchers only pinpointed characteristics and EMMs that demonstrated statistically significant associations (P < .05), potentially excluding certain prognostic factors owing to the impact of sample and effect size. The group also noted that most patients included in the studies assessed in the review were White or Asian, potentially limiting the generalizability of their findings to other racial and ethnic groups.

References

1. von Tresckow B, Abrisqueta P, Zamanillo I, et al. Prognostic factors and effect modifiers in patients with relapse or refractory diffuse large B-cell lymphoma after two lines of therapy: a systematic literature and expert clinical review. Eur J Hematol. Published online May 9, 2025. doi:10.1111/ejh.14423
2. Agrawal S, Arora S, Amiri-Kordestani L, et al. Use of single-arm trials for US Food and Drug Administration drug approval in oncology, 2002-2021. JAMA Oncol. 2023;9(2):266-272. doi:10.1001/jamaoncol.2022.5985