High-grade B-cell lymphoma: how to diagnose and treat

ABSTRACT

Introduction: High Grade B-cell Lymphomas (HGBL) have been defined as a new separate entity in 2016 revised WHO classification of lymphoid neoplasms. The previously well-known Double- and Triple-Hit Lymphomas (DHL/THL) are included in this umbrella category under the name of HGBL with MYC and BCL2 and/or BCL6 rearrangements (HGBL, R). A comprehensive diagnosis of HGBL is laborious, the diagnostic analyses required are expensive and time-consuming; moreover, a uniform consensus on which patients should be investigated has not been reached yet. Furthermore, there is no agreement on a standard therapeutic approach for this entity.

Areas covered: In this article, the biological and clinical peculiarities of HGBL will be reviewed and all tools for a comprehensive diagnosis as well as the current therapeutic landscape will be investigated.

Expert opinion: HGBL, R remains a challenging disease in terms of diagnosis and further research should be performed in order to define clear guidelines determining which cases have to be investigated thoroughly with FISH and other probes. Unsatisfying results have been shown in patients with HGBL, R treated with intensified chemoimmunotherapy strategies, therefore, larger prospective clinical trials should be conducted. Investigation into novel drugs that could lead to improvement of the current therapeutic approach should also be addressed.

KEYWORDS:

• High-grade B-cell lymphoma
• double hit lymphoma
• B-cell aggressive lymphoma
• intensive chemoimmunotherapy

Article highlights

• HGBL has been defined as a new separate category in 2016 revised WHO classification of lymphoid neoplasms, including in this entity HGBL, R (previously well known as Double and Triple Hit Lymphomas, DHL and THL).

• A comprehensive diagnosis of these entities is laborious and includes an accurate morphologic description and several additional analyses, such as FISH. However, identifying which patients these analyses should be addressed is still a challenge.

• HGBL, R are characterized by highly aggressive clinical course and tendency towards chemo-refractoriness and early relapses.

• A standard therapeutic approach has not been defined yet. Standard chemoimmunotherapy as R-CHOP is largely unsatisfactory. Intensified chemoimmunotherapy approaches, including Burkitt-like regimens, have been investigated and should be preferred even if data showed improved, but not yet satisfying results. Consolidation with ASCT did not demonstrate a gain in terms of survival and could be considered in restricted cases such as in patients who obtain less than CR after the induction therapy.

• Ameliorating the dismal prognosis still remains a critical unmet clinical need and novel drugs could hopefully have a key role in the improvement of the current therapeutic approach.

Declaration of interest

A Chiappella has acted on advisory boards for Celgene and Janssen. She has also received lecture fees from Amgen, Celgene, Janssen, Nanostring, and Roche. U Vitolo has acted on advisory boards for Roche, Janssen, and Celgene and has received lecture fees from Roche, Celgene, Janssen and Gilead. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

A peer reviewer on this manuscript is an employee of Walter and Eliza Hall Institute and as such, is potentially eligible for Royalty payments in relation to venetoclax. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.