Abstract

Background: Almost half of patients with diffuse large B-cell lymphoma (DLBCL) will have relapsed/refractory (R/R) disease after frontline immunochemotherapy. Although guidelines recommend histological confirmation of R/R disease, repeat biopsies are not always performed. Aims: To better appreciate the extent and reasoning for not performing repeat biopsies in R/R DLBCL. Methods: We conducted a two-part study: (1) using a nationwide electronic questionnaire consisting of 8 clinical vignettes, we evaluated the views of practicing hematologists in Israel regarding the need for repeat biopsies in suspected R/R DLBCL; (2) a single center retrospective study was utilized to describe real-life clinical practice patterns of performing procedures aimed at achieving tissue diagnosis for relapsed/refractory aggressive NHL (aNHL) patients: we included all consecutive adult (≥18 years of age) patients diagnosed with aNHL treated at a tertiary center in Israel, between 1/1/2013 and 1/1/2020, we identified patients who were diagnosed with R/R disease and analyzed data pertaining to utilization of histological confirmation via repeat biopsy. Each timepoint of management decision regarding biopsy performance was considered as a separate “episode of R/R lymphoma”. We extracted data regarding reasons for not performing the biopsies from the computerized system, according to the treating physician. Results: In the survey part, all 64 participating physicians opted not to perform a repeat biopsy in at least one clinical case scenario. Physicians’ age, gender, tenure or clinical experience with DLBCL patients did not correlate with the decision to perform a biopsy, whereas more physicians chose to perform biopsies in relapsed compared to refractory disease cases. In the retrospective part, 116 episodes of R/R aNHL among 61 patients were identified. In 72% of these episodes a repeat biopsy was not performed, mostly due to low likelihood of an alternative diagnosis or problematic location for biopsy. Patients with relapsed disease were more likely to undergo biopsy, as compared to those with refractory disease (47% vs 19%, p=0.002). Focusing on the group of patients with DLBCL (excluding primary CNS lymphoma, primary mediastinal B cell lymphoma and Burkitt lymphoma), there were 43 patients with refractory (n=26) or relapsed (n=17) DLBCL. In 61.4% out of the 83 episodes of R/R disease in these 43 patients, a biopsy was not performed: 74.5% of refractory DLBCL episodes versus 35.7% of relapsed DLBCL episodes (p=0.001). Stratifying biopsy utilization for each patient according to the timing of event, i.e first, second or third event of R/R disease, revealed that less biopsies were performed at more advanced relapse episodes. The most common reason for not performing a repeat biopsy was having stable radiological findings and other diagnoses deemed unlikely, as depicted in Figure 1. Image:Summary/Conclusion: Our study suggests that contrary to guideline recommendations, in clinical practice many patients do not undergo repeat biopsy in R/R DLBCL, especially in refractory cases. Since this is a common dilemma faced in clinical practice, future studies and recommendations should address the necessity of repeat biopsy, according to patient and disease related characteristics.

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