Approaching DLBCL: Risk Assessment and Prognosis

EP: 1.Case Overview: 77-Year-Old Woman With DLBCL

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EP: 2.Approaching DLBCL: Risk Assessment and Prognosis

EP: 3.DLBCL: Cytogenetic Testing and Treatment Initiation

EP: 4.Frontline Treatment Approaches in DLBCL

EP: 5.Current Treatment Approaches for R/R DLBCL

EP: 6.Implications for Treating R/R DLBCL With the L-MIND Regimen

EP: 7.R/R DLBCL: Observations From the Re-MIND Study

EP: 8.R/R DLBCL: Treating With Tafasitamab Plus Lenalidomide

EP: 9.Progress Made in Treating R/R DLBCL

John M. Burke, MD: When assessing risk in a patient with newly diagnosed diffuse large B-cell lymphoma [DLBCL] we still use the old-fashioned International Prognostic Index [IPI] or the Revised International Prognostic Index [R-IPI]. This consists of 5 factors, abbreviated as APLES, which is age, performance status, LDH [lactate dehydrogenase], extranodal sites, and stage. I think almost all oncologists are familiar with this clinical score, and it’s still used in clinical practice today.

Patients with poor-risk disease, as this patient had, have an estimated 4-year progression-free survival of about 50%. Besides the IPI score, another thing that I think is important to look at is cell of origin. In clinical practice, we estimate the cell of origin using immunohistochemistry [IHC]. Initially, the cell of origin was described by gene expression profiling and classified as germinal center B [GCB], activated B-cell subtype, primary mediastinal subtypes. When using IHC, we estimate that as being either germinal center B or nongerminal center B. So that’s important to look at. We know that the nongerminal center B subtype, or the activated B-cell subtype, has a less favorable prognosis than the germinal center B subtype, for the most part.

Another important factor to think about when you have a newly diagnosed patient is whether the patient has so-called double hit or triple hit DLBCL, meaning there’s a combination of rearrangements in the MYC gene plus either the BCL2 or BCL6 genes, or both. Having 2 rearrangements is called double hit, and having 3 rearrangements is called a triple hit. Those patients have a particularly unfavorable prognosis and may be more appropriately treated with more aggressive chemotherapy regimens than R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine and prednisolone].

The final thing I’d point out is that I think it is important to remember to try to calculate the CNS [central nervous system] relapse risk in newly diagnosed DLBCL patients. In clinical practice, that might get forgotten. The NCCN [National Comprehensive Cancer Network] has listed a formula on its website. Basically, you get a point for various things, some of which are already in the IPI, and there are additional points for kidney or adrenal involvement. There are certain patients who may automatically, by their diagnosis, benefit from CNS prophylaxis. So it is important for practitioners to remember to calculate that CNS relapse risk score and, for high-risk patients, consider some type of CNS prophylaxis along with treatment.

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