How to treat newly diagnosed DLBCL

During the Lymphoma Hub Steering Committee meeting, key opinion leaders met to discuss how to treat newly diagnosed diffuse large B-cell lymphoma (DLBCL). This recorded discussion was chaired by Gilles Salles and featured Grzegorz Nowakowski, Catherine Thieblemont, Andrew Davies, Astrid Pavlovsky, Kieron Dunleavy, Marek Trněný, Miles Prince, Alison Moskowitz, and Martin Dreyling.

Salles asks the committee how the treatment of patients with DLBCL varies in different countries, including the categorization of patients into various groups and what key factors are taken into consideration. The committee focus on the current use of clinical pathology for the diagnosis of subtypes and how this has an influence on determining first-line therapy, particularly in selecting treatment choices in patients without significant comorbidities.

Key points

The committee discuss how factors, including a patient’s age, overall performance status, progression-free survival, comorbidities, and treatment desires, are crucial in determining first-line treatment considerations. Thieblemont adds how the International Prognostic Index (IPI) and Trail Making Test B (TMBT) are utilized in accessing risk factors and disease progression to better tailor initial treatment regimens.

The committee go on to deliberate how identifying the molecular phenotypes of DLBCL and the general pathology of disease has an impact on first-line therapy. Davies highlights how the active B‑cell (ABC) subtype of DLBCL is associated with poorer outcomes when subjected to treatment with a standard therapy, such as bortezomib. This leads to the committee mentioning the importance of determining the cell of origin via the use of transcriptional profiling, as opposed to using immunohistochemical surrogate, to give a binary conclusion on determining germinal center of DLBCL in diagnosis.

Likewise, the committee further discuss the urgency of starting treatment based on an initial PET-CT scan alongside any abnormalities seen in results received from laboratory testing. The use of fluorescence in situ hybridization (FISH) to detect MYC gene abnormalities and how this should be followed by BLC2 testing as well as measuring lactate dehydrogenase (LDH) levels are also mentioned as forms of prognostic testing to better understand the molecular make up and to help the identification of subtypes. Additionally, the committee converse about difficulties regarding the spectrum of diseases as different patients have varying features from double-hit lymphoma with high proliferation rate to high grade B-cell lymphoma not otherwise specified (HGBCL-NOS) and how this has brought about recent challenges in the incorporation of new classifications alongside the preexisting characteristics to include subtypes as DLBCL.

The committee finish by discussing how to treat patients who do not have significant comorbidities in a first-line setting, mentioning how the standard R-CHOP regimen is the only current real-world option outside of clinical trials and how it is vital to consider prognostic features and early response to treatment. Touching on how the current treatment regimens in elderly patients are still limited, the committee bring to light that elderly patients may have new chemo-free regimens available in the near future based on the accumulating data being gathered from recent clinical studies. Prince remarks on the controversy around how to treat specific subtypes with the use of chemotherapy, radiotherapy, and radiation in a first-line setting and how this varies from patient to patient. The committee also briefly mention how the recent approval of polatuzumab alongside standard use of R-CHP is being better tolerated.

Key takeaways:

• Patients with DLBCL should be treated as a medical oncology emergency.
• R-CHOP remains a first-line option for a vast majority of patients.
• Advanced disease needs a better understanding of disease biology and handling novel treatment strategies. For example, the recently approved polatuzumab alongside standard use of R-CHP is being better tolerated.
• CAR T-cell therapy should be introduced as a second-line option for patients who are refractory to or failing therapies.