A Case of Relapsed/Refractory Diffuse Large B-Cell Lymphoma


Expert hematologist/oncologist Daniel O. Persky, MD, reviews the case of a 73-year-old woman who is diagnosed with and treated for DLBCL, later to relapse and require novel therapy.

Daniel O. Persky, MD: It’s my pleasure to discuss with you a case of a 73-year-old woman with diffuse large B-cell lymphoma [DLBCL]. She presented with progressive fatigue [and] enlargement of lymph nodes in the neck and groin. She had a past medical history of coronary artery disease, stage II chronic kidney disease, [and] type 2 diabetes mellitus controlled with oral medications. On physical examination, she had palpable bilateral cervical and inguinal lymphadenopathy, as well as splenomegaly. Her ECOG performance status was 2.

On clinical work-up, she had anemia with hemoglobin of 9.9 [g/dL], elevated LDH [lactate dehydrogenase] at 290 [U/L], with the rest of the CBC [complete blood count] and comprehensive metabolic panel within normal limits. Hepatitis B, [hepatitis] C, and HIV serologies were negative. An excisional biopsy of her cervical lymph node showed [DLBCL], with the immunohistochemistry showing non-GCB [non-germinal center B-cell-like] subtype by Hans algorithm and FISH [fluorescence in situ hybridization] showing translocation of BCL6, but no translocation of c-MYC or BCL2. Her flow cytometry was positive for CD19.

Her whole-body PET [positron emission tomography]/CT scan showed diffuse lymphadenopathy and splenomegaly with SUV [standardized uptake value] max of 16.3 and the largest lymph node being 3.8 cm. Her Lugano stage was III, and her IPI [International Prognostic Index] score was high intermediate. She was treated with 6 cycles of R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone], and her end of treatment PET/CT scan showed complete remission. However, 9 months later, she presented with enlarged lymph nodes again, and her repeat biopsy confirmed DLBCL, again, non-GCB subtype. And again, FISH was negative for c-MYC translocation. The patient was not eligible for high-dose chemotherapy followed by autologous stem cell rescue based on her physiologic age and comorbidities. She proceeded with treatment with polatuzumab in combination with bendamustine and rituximab.

Let’s discuss a little bit about risk assessment for DLBCL. At this point in time, DLBCL is a family of diseases that continues to evolve, and [the] number of types continues to multiply as we understand more about the pathology of the disease. Of course, we have basic clinical characteristics, which are still true, and they’re still prognostic, which go into our International Prognostic Index, or IPI. This has undergone revisions, such as the revised IPI and NCCN [National Comprehensive Cancer Network]-IPI, but there’s also second-line IPI for patients with relapsed disease, which is also valid. We know at this point in time, that cell of origin designates different types of [DLBCL], and those are germinal center-derived and activated B-cell type. These are now part of the official WHO [World Health Organization] classification of DLBCL. Assessment of cell of origin is now a standard part of the work-up. Then, the next point is of course the presence of double- and triple-hit lymphoma.

These are colloquial terms that designate the presence of c-MYC translocation, in addition to BCL2 or BCL6 rearrangement for a double-hit lymphoma, and all 3 translocations or rearrangements for triple-hit lymphoma. Technically, now the presence of double- or triple-hit indicate a lymphoma called high-grade B-cell lymphoma, with c-MYC and BCL2 and/or BCL6 rearrangement. But we still consider it as part of the broader [DLBCL] family, although we know it’s prognostically more favorable than a DLBCL not otherwise specified. A lot of these factors have been examined in first-line therapy, but as I pointed out, just like with IPI, there’ve been studies showing the importance of those prognostic factors in relapse. Cell of origin and double- or triple-hit status are also prognostic in relapse as well.

This transcript has been edited for clarity.

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