The following article features coverage from the American Society of Hematology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

A real-world analysis found that as many as 56% of patients with diffuse large B-cell lymphoma (DLBCL) were found to have double expression of BCL2 and MYC when analyzed by immunohistochemistry (IHC) compared with historical rates of expression of closer to one-third.

“This is likely due to our cohort of patients requiring both IHC and molecular testing to have been performed, which NCCN [National Comprehensive Cancer Network] guidelines state should only occur in DE [double expression] patients with GCB-like immunophenotype,” the researchers wrote in an abstract presented at the 61st ASH Annual Meeting and Exposition in Orlando, Florida. “However, even in a cohort enriched with DE and GCB patients, 38% of the DE/TH [double-hit/triple-hit] patients would not have been detected with current NCCN testing guidelines, which restrict only to those who were DE with a GCB-like immunophenotype.”

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According to the abstract, current NCCN guidelines recommend IHC testing for MYC and BCL2 for all patients and additional testing by FISH or karyotype analysis in patients with both IHC-positive results for MYC and BCL2 and a GCB immunophenotype.

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This retrospective study analyzed data from 5747 patients with a diagnosis of DLBCL based on ICD9 or ICD10 codes between January 2011 through June 2019. Information on cell of origin, IHC, karyotype analysis and FISH testing was abstracted from pathology reports or clinical visit notes. The researchers selected patients who had results for 1) MYC by IHC, 2) MYC by molecular testing, 3) BCL2 by IHC, and 4) either BCL2 or BCL6 by molecular testing.

Of the patients, 778 had results for the qualifying tests. For the double-hit/triple-hit patients, 36% were cytogenetically tested under NCCN guidelines. However, 64% were not double expressors with a GCB-like immunophenotype, and would have been missed with current testing guidelines.

Overall, 108 patients with DLBCL were determined to have double-hit or triple-hit disease — and 38 of these 108 patients, or 35%, would not have been diagnosed based on current testing guidelines.

“This analysis reflects several factors encountered in real-world cohorts, such as the variability in practice patterns relative to professional guidelines, or practical challenges in the standardization of IHC testing,” the researchers noted in the abstract. In the poster, they added that in order to improve the detection of DH/TH disease, “Guideline panels may want to consider expanding cytogenetic testing recommendations.”

Disclosure: Some of the authors disclosed financial relationships with Roche and Flatiron Health, Inc., which is an independent subsidiary of the Roche Group. For a full list of disclosures, please refer to the original abstract.

Read more of Cancer Therapy Advisor‘s coverage of ASH’s annual meeting by visiting the conference page.


Hooley IJ, Parrinello CM, Opong AS, et al. Real-world application of National Comprehensive Cancer Network (NCCN) testing guidelines in diffuse large B-cell lymphoma (DLBCL) results in underdiagnosis of double-hit lymphoma. Presented at: 61st American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract 3426.