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Chief, Division of Oncology and Hematology
Neumann M. and Mildred E. Harris Professor
Department of Internal Medicine
University of Nebraska Medical Center
Julie M. Vose, MD, MBA, has disclosed that she has received funds for research support from Acerta/AstraZeneca, Celgene/Bristol-Myers Squibb, Epizyme, Incyte, Kite, Loxo, Novartis, and Seattle Genetics and consulting fees from AbbVie, Acerta/AstraZeneca, Conjupro, Janssen/Pharmacyclics, Johnson & Johnson, Kite, Morphosis, Oncternal, Roche/Genentech, and Vaniam Group.
Below, I share how I diagnose diffuse large B-cell lymphoma (DLBCL) and sequence treatments for patients with DLBCL.
Hematopathology Review of Biopsies
Accurate diagnosis and pathologic workup are essential for B-cell lymphomas. It is very important to get a good lymph node biopsy with adequate tissue for all the hematopathology analyses required to characterize the molecular subtype of DLBCL and determine the tumor’s mutational status. In my practice, we work with an expert hematopathologist to perform appropriate immunohistochemistry and other staining to differentiate between activated B‑cell subtype and germinal center B‑cell molecular subtypes. In addition, we use immunohistochemistry to assess for expression of various markers, including CD20, CD3, CD5, CD45, BCL2, BCL6, Ki-67, and/or MYC proteins, followed by fluorescence in situ hybridization testing to determine whether there are translocations/rearrangements in MYC, BCL2, and BCL6. Patients with double- or triple-hit lymphoma have a poorer prognosis, and they often are eligible for clinical trials.
A PET/CT scan is important to determine the extent of disease for staging patients with DLBCL, and a bone marrow biopsy also may be needed to detect bone marrow involvement unless there is positive bone marrow uptake on PET/CT imaging. Blood tests for complete blood count, chemistry profile, and lactate dehydrogenase (LDH) also are needed to put together an International Prognostic Index (IPI) for the patient.
In general, patients who do not have double- or triple-hit DLBCL can begin treatment with R-CHOP, which for now remains the standard of care. For patients who are double or triple hit, I would consider dose‑adjusted R‑EPOCH if the patient is clinically able to tolerate more aggressive therapy. However, many patients with DLBCL who receive upfront chemoimmunotherapy experience relapsed disease.
For patients with more extensive disease (stage III-IV), radiation can be considered after 6 cycles of chemoimmunotherapy. For patients with localized disease, 3 cycles of R-CHOP followed by radiation or 4-6 cycles of R-CHOP with or without radiation can be considered. Radiation is generally considered in patients with bulky disease (>10 cm at the time of diagnosis).
Multiple ongoing clinical trials are exploring additional treatment options for patients with previously untreated DLBCL. For example, there currently is an ongoing clinical trial with R‑CHOP plus the BCL2 inhibitor venetoclax for patients with newly diagnosed double-expressor DLBCL. Data from another study of DA-EPOCH-R with or without venetoclax with newly diagnosed double-hit lymphoma are being presented at the 2021 American Society of Hematology Annual Meeting and Exposition. Polatuzumab vedotin, an antibody‒drug conjugate targeting CD79b, is approved in relapsed/refractory DLBCL in combination with bendamustine/rituximab, and data from the phase III POLARIX trial evaluating polatuzumab vedotin plus R-CHP for previously untreated DLBCL also are being presented. If progression-free survival is significantly improved in these types of trials, this could change our practice for upfront treatment.
After first-line therapy is complete, repeat PET scan restaging can be considered. For patients who achieve a complete response, typically that would be the end of their treatment. Patients with a partial response or no response to treatment should undergo additional therapy as described for relapsed disease.
Treating Relapsed DLBCL
For patients who experience relapse or whose DLBCL does not achieve remission from the initial treatment, salvage chemotherapies typically are considered and may include R‑GDP, R‑GemOx, and R‑ICE. For patients who achieve a complete response or partial response, autologous stem cell transplant would be the next decision. For patients with no response or progression, CAR T‑cell therapy should be considered. Current CAR T-cell treatment options include axicabtagene ciloleucel, lisocabtagene maraleucel, and tisagenlecleucel.
If a patient receives an autologous stem cell transplant and then relapses, they should receive CAR T-cell therapy if they are a candidate. If there is relapse after CAR T-cell therapy, the patient may be eligible for enrollment on a clinical trial evaluating bispecific antibodies or other novel therapies. Patients who are not eligible for transplants or CAR T‑cell therapy also may be eligible for clinical trials, and there are other less aggressive treatment regimens, such as lenalidomide plus tafasitamab, polatuzumab vedotin plus bendamustine/rituximab, or polatuzumab vedotin plus rituximab alone. Loncastuximab tesirine is another treatment option and recently received accelerated FDA approval based on data from the LOTIS-2 trial. Selinexor is approved by the FDA for the third line and beyond.
What questions do you have on managing patients with DLBCL?
Do you want to learn more about optimizing the care of patients with DLBCL? Sign up here to attend the live symposium or simulcast webinar “A Class in Session: Understanding Current and Future Therapeutic Advances Across B-Cell Lymphomas” on Friday, December 10, 2021, at 7:00 PM Eastern time with me and my colleagues, John P. Leonard, MD, and Brad S. Kahl, MD, where we will discuss the available evidence, key ongoing clinical issues, and new data across different B-cell lymphomas.