December 11, 2023
By Catlin Nalley
Data from a recent analysis that examined the impact of the differences between the two new classifications on real-world diagnosis of non-Hodgkin lymphoma (NHL) were presented during the 65th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 9-12 in San Diego (Abstract 3708).
“The use of standardized, evidence-based classification systems is crucial for the accurate diagnosis and treatment of diseases. Moreover, standardized classification facilitates research and epidemiologic studies and promotes consistency in communication among health care professionals,” noted study author Brooj Abro, MD, Assistant Professor in the Department of Pathology and Laboratory Medicine at Emory University School of Medicine, along with her colleagues.
The revised 4th edition of the World Health Organization classification (WHO-HAEM4R) has been the global standard for diagnosis of lymphoid malignancies since 2016, they explained, while also highlighting that new data led to the development of two new classification systems in 2022—the 5th edition of the WHO Classification (WHO-HAEM5) and the International Consensus Classification (ICC).
“Both WHO-HAEM5 and ICC maintain a shared fundamental concept of disease classification that integrates clinical, pathologic, and molecular data,” Abro and team said. “However, they differ on nomenclature, establishment of new entities, and/or diagnostic criteria for some disease categories.”
The investigators used the diagnostic classification of NHL in the Lymphoma Epidemiology of Outcomes (LEO) Cohort Study (NCT02736357) to better understand the impact of the differences between these classification systems on real-world non-Hodgkin lymphoma diagnosis. LEO, an ongoing, prospective, observation study of adult patients with newly diagnosed non-Hodgkin lymphoma from eight major U.S. medical centers, was started in 2015.
At baseline, researchers abstracted clinical, epidemiologic, pathologic, and treatment data. All patients undergo active follow-up. Expert hematopathology re-review of the diagnostic pathology slides, the pathology report, biomarker data, and clinical data is conducted to code the lymphoma subtype for each case.
Abro and colleagues analyzed all patients who were enrolled in the LEO study between July 1, 2016, which is the data LEO pathology review started using WHO-HAEM4R diagnostic codes, and May 31, 2020. “WHO-HAEM4R diagnoses and additional clinicopathologic data, when relevant, were used to map cases into the corresponding WHO-HAEM5 and ICC diagnoses,” they stated.
During the study period, 6,143 patients were enrolled in LEO. Of these patients, 5,730 (93.3%) were evaluable for comparison between WHO-HAEM5 and ICC. When the researchers looked at the evaluable cases, they observed no difference between WHO-HAEM5 and/or ICC diagnosis in 5,376 (93.8%). Additionally, 311 (5.4%) showed minor differences in nomenclature only, and 43 (0.8%) had major differences, they reported.
“The 43 major differences all involved B-cell NHLs; 20 (46.5%) were attributable to different approaches to classifying double-hit lymphomas, 21 (48.9%) to classification of splenic/leukemic B-cell lymphomas, and 2 (4.6%) to classification of B-cell lymphomas occurring at specific anatomic sites,” Abro and investigators outlined.
In summary, this large, prospective cohort of real-world lymphoma patients revealed major differences in the classification of non-Hodgkin lymphoma using WHO-HAEM5 or ICC classification criteria were observed in 0.8 percent. The remaining 99.2 percent of diagnoses were either the same or showed differences in nomenclature only, according to the study authors.
“The existence of two concurrent classification systems presents potential for discrepancies in pathologic diagnosis, clinical practice, clinical trials, and other lymphoma research,” noted Abro and colleagues. “Furthermore, some of the differences between WHO-HAEM5 and ICC are clinically and potentially therapeutically significant and their resolution requires further study.
“Nevertheless, our findings argue that the proportion of patients affected would be small in real-world practice settings,” they concluded. “This appears largely related to incidence rates of specific lymphoma subtypes, with major differences between the two classifications predominantly affecting rare entities, while there is general concordance on the most common forms of non-Hodgkin lymphoma.”
Catlin Nalley is a contributing writer.