A 77-Year-Old Woman with DLBCL - Episode 3

DLBCL: Cytogenetic Testing and Treatment Initiation

John M. Burke, MD: In my hospital, the timing on FISH [fluorescence in situ hybridization], from the biopsy to when I get the results back, tends to be between 1 and 2 weeks. It’s usually not more than that. My hospital is sending FISH testing out to central laboratories around the country, so there is shipping involved.

Most of the time, when a patient is newly diagnosed, it still takes some time to get them coordinated for treatment. They have to undergo a PET [positron emission tomography]/CT scan. They have to get labs drawn. They have to learn about the disease. They have to learn about adverse effects. All of that takes enough time for which, in my practice, usually the FISH result is back before I need to initiate therapy.

There are occasions when patients need to be treated quickly because they’re so sick. We have to start them on treatment in the hospital before we have FISH results back. However, I would say that’s the minority. In the case where someone is in that situation and gets a cycle of R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone], and then, low and behold, the FISH comes back showing a double hit and you want to use a more aggressive regimen, I don’t lose any sleep if they got 1 cycle of R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone]. I can use a more aggressive regimen for all of their subsequent treatments. I don’t think it’s a big deal if the FISH results take a little bit longer, but most the time I have results back, even in a community practice like mine.

The question as to whether I do additional molecular testing in diffuse large B-cell lymphoma besides the FISH, my answer is generally not. You ask, what kind of molecular testing are we talking about? One is gene expression profiling, and generally that is not performed outside of clinical trials. To date, distinguishing the gene expression profile has not changed the treatment regimen that we use. We use the same, R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone], for germinal center B-cell subtype that we use for nongerminal center B subtype. Although attempts have been made to change the treatment, particularly for the nongerminal center B, or activated B-cell subtype, none of those trials have turned out positive so far. So that doesn’t really affect clinical practice.

The other rationale that one might think about for using the next-generation sequencing panel would be to calculate the m7-FLIPI [Follicular Lymphoma International Prognostic Index] score. M7-FLIPI refers to 7 gene mutations that can be incorporated into a calculation to further refine a prognosis in follicular lymphoma. This is not really used in large cell lymphoma, but more so for follicular lymphoma. But again, it’s not a perfect test. It doesn’t have a lot of impact in clinical practice, so I’m not generally doing molecular profiling in my large cell lymphoma patients, or in my follicular lymphoma patients either.

Transcript edited for clarity.


Case: A 77-Year-Old Woman With DLBCL

Initial Presentation

  • A 77-year-old woman presented with loss of appetite, fatigue and shortness of breath
  • PMH: post-menopausal; DM, medically controlled
  • PE: palpable inguinal lymphadenopathy; splenomegaly
  • ECOG PS 1

Clinical Work-up

  • Labs: Hb 9.8 g/dL; all others WNL
  • FEV1 45 %
  • Hepatitis B, C and HIV negative
  • Core needle biopsy of the inguinal node: CD20-positive diffuse large B-cell lymphoma, non-GCB subtype. FISH panel: t(14;18) with a BCL2 rearrangement; no MYC or BCL6 rearrangement
  • Imaging:
    • Whole body PET/CT scan showed FDG avidity the inguinal lymph node region, largest node 3.3 cm; splenomegaly; and a small suspicious lung lesion
  • Bone marrow biopsy: involvement with DLBCL
  • Conclusion: stage IV DLBCL, non-GCB subtype
  • IPI score high-risk; CNS relapse score intermediate risk

Treatment

  • Treated with R-CHOP for 6 cycles
  • End-of-treatment PET/CT demonstrates a Deauville 2 complete remission
  • 1 year later while in surveillance she presents with new cervical, axillary, mediastinal, and abdominal lymphadenopathy
  • Core needle biopsy of an axillary node confirms a relapse of DLBCL, non-GCB subtype
  • Based on her age of 78 years and performance status, you consider her to be transplant-ineligible
  • You elect to initiate tafasitamab + lenalidomide