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
Clinical Work-up
Treatment
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