Expert Discusses Treatment With BV+AVD Regimen in a Classic Hodgkin Lymphoma Case Study

<< Back to all news Jonathon B. Cohen, MD, MS Jonathon B. Cohen, MD, MS, explained to a group of physicians in a recent Targeted Oncology live case-based peer perspectives presentation the diagnostic workup and treatment considerations and decisions he makes when seeing a patient with Hodgkin lymphoma in the clinic. Cohen, an assistant professor of hematology and medical oncology at Emory University School of Medicine and medical director of infusion services at the Winship Cancer Institute of Emory University, discussed treatment options in relation to a case scenario of a patient with classic Hodgkin lymphoma (cHL).

Case

A 22-year-old women presented with right-sided cervical nodes developing over several months. She was initially evaluated by her obstetrician-gynecologist, who recommended observation. She subsequently developed neck pain while drinking wine. She was referred for lymph node biopsy. Test results confirmed that she had cHL.

She had no medical or surgical history. Her only regular medication was oral contraceptives; she had no known drug allergies. She had no history of tobacco use but had occasionally drank alcoholic beverages. She was a division 1 collegiate swimmer. Her family history of cancer diagnoses included a maternal grandfather with squamous cell cancer, maternal grandmother with melanoma, and an aunt with breast cancer. She had 2 healthy siblings.

Laboratory findings were notable for a white blood cell (WBC) count of 19.8 × 10 9 /L (85% polymorphonuclear cell count ); hemoglobin, 12.0 g/dL; platelets, 571,000 mcL; erythrocyte sedimentation rate, 30 mm/hr; creatinine, 0.76 mg/dL; albumin, 4.2 g/dL. She was negative for HIV/hepatitis.

PET/CT staging showed intrathoracic diffuse adenopathy; right-sided cervical nodes, 2.3 × 1.9 (standardized uptake value [SUV], 9.3); left-sided cervical nodes, 2.2 × 1.8 (SUV, 8.8); anterior mediastinum, 4.8 × 2.9 (SUV, 21.3); right-sided axillary, 2.8 × 2.8 (SUV, 12.2); spleen normal size (SUV, 2.9); diffuse uptake in the axial skeleton (SUV, 4.9-5.5); mediastinum, SUV 1.8; liver, SUV 2.4. She received a pathologic diagnosis of nodular sclerosis cHL.

Per immunohistochemistry (IHC), the Hodgkin cells expressed CD30, CD15, and PAX5 (weak), and were negative for CD3, CD20, and CD45.

What is the prognosis for this patient?

Her labs showed a leukocytosis, an elevated platelet count, and then she had a staging PET/CT that showed some diffuse adenopathy. There was some diffuse uptake in the axial skeleton; not necessarily a lot of local findings but some increased uptake. You can see she had a number of areas, including in the mediastinal, that were highly 18 F-FDG [fludeoxyglucose] avid. The pathology review came back as nodule sclerosis cHL with a fairly classic IHC report.

Do you typically calculate a prognostic score for each patient?

Although I often consider what the prognostic score may be, depending on the situation with the patient and how in depth they want to get with their own prognosis, it does not necessarily markedly affect my treatment decision.

There is an international prognostic score for Hodgkin lymphoma that can be used. 1 Sometimes I will have patients that have come and have researched it themselves or will have more specific questions about it. Because it does not typically influence the treatment decision that I make, I do not dwell on it when I am talking with the patient.

How do the results of the PET/CT affect treatment selection in this patient? What disease stage is this patient in?

This is someone who presented with advanced-stage cHL. [She is a] young, healthy person, so she can really have any potential therapy that you would think about.

This is an unusual case because you have this bony uptake. It is unclear whether there is marrow involvement versus bone involvement or whether it was anything at all—in this particular case, someone who has not been on growth factor and has not had some other indication for why they have uptake and has other signs of advanced stage disease. You do not want to necessarily do a biopsy in that case because this is a patient who has fairly diffuse adenopathy, so you are treating them as an advanced stage case.

Similarly, at least for me, I do not always get a bone marrow biopsy for patients with Hodgkin lymphoma because it is not commonly involved, and it does not make a big difference in the treatment. When I look at this, I would probably consider this patient as a stage IV. Someone else could look at it and say, “Maybe there is uptake for unclear reasons; maybe it is a stage III,” but I would consider them either a stage III or IVa.

Would you do a bone marrow biopsy based on what was shown on the PET/CT?

This is somebody that could technically be earlier stage, because you really do not think the axial skeleton is involved. I think in a case like this, especially with a young patient in the absence of some other clear indications for why it would be there, I would typically consider them to have bone involvement. But that would be a judgment call, and somebody could look at it and feel otherwise. In this case, it does not look like the patient has had that done. But in that specific scenario where you are thinking, “Is the PET scan showing some marrow involvement?” that [may determine] if I want to treat them as having early stage disease or not.

My personal sense is that for somebody who comes in with a fairly straightforward case, I do not think a bone marrow biopsy is typically required. In this case, if you were to see this situation and think, “I would like to get a marrow just to get a better sense of what is going on in the bones,” I think that would be reasonable here.

I have not traditionally done [an MRI of the spine] to confirm whether or not the patient has marrow involvement. Now, if you did that and you saw some convincing bone lesions, you could potentially then get by without doing the marrow. It is a tough call.

What are the systemic options in frontline therapy for this patient?

One of the big questions here, especially with the recent approval of brentuximab vedotin [Adcetris; BV] in the frontline, is whether you would use BV plus doxorubicin, vinblastine, and dacarbazine [AVD], or would you use ABVD [doxorubicin, bleomycin, vinblastine, and dacarbazine], and how would you do it? If I were seeing this person, I would have these questions. I think that if you did not have a trial or they declined a trial, there are 2 good options. For most patients in this setting, we will try to avoid bleomycin if at all possible, given that she is an athlete and for whom even a subtle change in the respiratory system could significantly affect her quality of life and her activity.

Case (continued):

The patient was treated with BV + AVD. An interim PET/CT scan showed a Deauville score of 3.

With a young patient such as this one, how do you handle the possible treatment-related impacts on her fertility?

For ABVD, there are pretty good data that would suggest that those patients will not have impaired fertility. There have been some cases of premature ovarian failure in women, so what I typically do is…have a discussion with them. If it is somebody who is in a position where having children in the future is important, I will refer them to a fertility specialist and will typically communicate to the specialist ahead of time that the incidence of infertility is low. It is always helpful for them to have that discussion.

Fortunately, most people treated with ABVD will have no problems and will conceive children naturally. In fact, with young people, I often spend a considerable amount of time in the room talking to them about the fact that you cannot rely on this as birth control. We have had patients that have gotten pregnant on treatment or shortly afterward. Fortunately, it does not happen that often, but it can happen. With ABVD, it is pretty clear that those patients will be fine. With BV + AVD, we do not have that same long-term data, but there is no indication that BV increases the risk of infertility.

If they can wait to see a fertility specialist and have a full evaluation and talk about options, I think that is always ideal. Then everyone feels comfortable with a chance to address that. In situations where people do not have the time or maybe they do not have the financial resources to go down that path, the data that have been pretty reassuring that they will be OK.

Discuss the role of the interim PET/CT results in patients taking BV + AVD.

This patient was treated with BV + AVD, and their interim PET/CT looks good with the Deauville score of 3. They tolerated the therapy well with GCSF support. One thing that is worth at least highlighting here is that initially when the ECHELON-1 study came out […]

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