Assessing Risk to Guide First-Line Treatment Selection in DLBCL

EP: 1.Case Review of a 71-Year-Old Woman Presenting With DLBCL

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EP: 2.Assessing Risk to Guide First-Line Treatment Selection in DLBCL

EP: 3.Second-Line Therapy Options in DLBCL

EP: 4.The L-MIND Trial in R/R DLBCL

EP: 5.Later Lines and Future Directions in DLBCL

Matthew Lunning, DO: When describing the risk factors for this individual’s lymphoma, one would be her advanced age, marching down the IPI [International Prognostic Index] score, greater than 60. Also, the staging of her disease. She had advanced stage disease with involvement of the bone marrow and likely involvement of the spleen, given that it was enlarged despite there being no avid bone lesions. I would consider doing bone marrow aspirates even if there’s no avid bone lesions in a patient who has anemia at the time of diagnosis. She also had an elevated LDH [lactate dehydrogenase]as well as extranodal sites of disease in the bone marrow biopsy and potentially spleen. In that regard, her performance status was acceptable at the time of diagnosis, so that would make her IPI score a 4 at this point.

Another part about the risk of her assessment of her diffuse large B-cell lymphoma is where she was treated. She was well at this time. Many times, patients treated as inpatients because the diffuse large B-cell lymphoma is making them sick or compressing the airways, may portend a worse overall outcome, as well as the time needed between diagnosis and treatment. Those patients who are started sooner may have overall, at least the literature has shown, they have a little better prognosis than if it takes weeks before you initiate therapy. I have used prognostic factors of the IPI as well as the FISH [fluorescent in situ hybridization]characteristics. If this individual had a double-hit lymphoma, meaning…a high-grade B-cell lymphoma harboring MYC and BCL2 or BCL6 rearrangements, I would consider that a potentially high-risk biologic feature. And in this case, if the patient is felt to be able to tolerate anthracycline-based therapy, I would discuss using dose-adjusted EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab] in this setting, noting that I would dose adjust based upon hematologic and systemic tolerance.

There are certain caveats regarding frontline therapy given that R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] vs dose-adjusted EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab] are my 2 standard regimens. If I do have time to wait for the molecular testing to come back, I would consider waiting to see whether I’m going to start R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] or dose-adjusted EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab]. Often if the patient is mildly symptomatic, I may use a prephase-like therapy with prednisone for 100 mg for 5 days. I haven’t classically introduced vincristine into that, which I know was the original prephase. Also, there can be some insight into whether there’s potentially a double hit based upon if your pathologists are able to do MYC expression. If there’s high MYC expression, high Ki-67, then it may portend that this could be a MYC-altered diffused large B-cell lymphoma from that standpoint.

Typical response rates that you could expect from R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone], when you’re dealing with diffuse large B-cell lymphoma, the intent is curative. In many situations we’re using full dose R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] or full dose-adjusted EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab], at least at the initial line of therapy. I focus more on the complete response [CR] rates, now that we’re talking about using responses in the Deauville scoring era and the PET positron emission tomography]/CT era. I would venture that you see metabolic CR rates in between the 60% to 80% range, depending upon the studies that you’re doing. The majority of the people following R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] chemotherapy for frontline diffuse large B-cell lymphoma will often have evidence of remission.

In this situation, the patient did have evidence of recurrent disease defined as diffuse large B-cell lymphoma. It’s important to point out that this was found on physical examination with cervical lymphadenopathy, and further radiographic evidence confirmed this, that the patient also went under a second biopsy. This can be important because sometimes people can have what we call retrograde transformations. If you note here on the initial presentation, there was evidence of a translocation 14;18 as well as BCL2 expression, which may denote that there could be a follicular lymphoma that this may have derived from. Or if it’s relapsing, there could be follicular lymphoma that’s relapsing and not necessarily diffused large B-cell lymphoma. In this case, we had the comment that the patient tolerated R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone] well, and she had a good performance status and no major toxicities during her R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone]. You could have the discussion, and in this setting, I would have the discussion, about second-line therapy, and autologous stem cell transplant as a curative-intent option.

Transcript edited for clarity.

Case: A 71-Year-Old Woman with R/R DLBCL

Initial presentation

• A 71-year-old woman presented with fatigue, weight loss and pruritus
• PMH: HTN, medically controlled
• PE: palpable axillary and femoral lymphadenopathy; palpable spleen 3 cm below the midclavicular line
• ECOG PS 1
  
  

Clinical Workup

• Labs: Hb 9.8 g/dL, LDH 2x ULN; renal and hepatic function WNL
• Hepatitis B, C and HIV negative
• Excisional biopsy of a right enlarged axillary lymph node confirmed DLBCL, GCB subtype
• IHC positive for: CD10, CD20
• FISH panel: t(14;18) translocation with BCL2 rearrangement, no MYC or BCL2 rearrangements
• Flow cytometry: CD19-postitive
• Whole body PET/CT scan showed FDG avidity in the bilateral axillary and femoral regions, largest lymph node 3.6 cm in right axillary space; splenomegaly
• Bone marrow biopsy showed involvement of DLBCL in the bone marrow
• Ann Arbor stage IVa DLBCL, GCB subtype
• IPI score high-risk

Treatment

• Treated with R-CHOP x 6 cycles
• First post-treatment PET/CT scan unremarkable; metabolic CR based on Deauville criteria
• 9 months later there was relapse of disease with new cervical and mediastinal lymphadenopathy
• Core needle biopsy of a cervical lymph node confirms a relapse of DLBCL, GCB subtype
• She was offered ASCT but deferred
• Initiated tafasitamab + lenalidomide