Effective Therapies in Classical Hodgkin Lymphoma

Jonathon B. Cohen, MD, MS:Fortunately, for classical Hodgkin lymphoma, we have a number of effective therapies, and most patients will be cured of their disease. However, it’s very important for each individual patient to identify their comorbidities, to take into consideration aspects such as their age and performance status, as well as a number of other things that you may want to consider, like whether or not, for example, they are a smoker and might be at increased risk for pulmonary toxicity or a diabetic that may be at increased risk for neuropathy. And so I often try to take into account a number of factors, both with regards to the disease as well with regards to the patient, when making a decision.

Fortunately, we have a number of effective therapies. Traditionally the treatment for advanced stage Hodgkin Lymphoma was a 4-drug regimen, ABVD [doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine], which was the standard for many years. And this is typically a therapy that’s given every other week for 6 months of treatment, or 12 treatments. This is typically well tolerated, but one of the big challenges with this particular therapy is that the bleomycin can certainly increase the risk of pulmonary toxicity, which can be a devastating complication for patients with classical Hodgkin lymphoma.

In recent years, there’s now been 2 subsequent studies that have identified alternative options for patients with classical Hodgkin lymphoma. The first is a… is based on a study called the Raffle Study, which used a PET-adapted approach to manage patients with classical Hodgkin lymphoma. In that particular approach, patients received 4 treatments with ABVD, or 2 cycles. And at the conclusion of those 2 cycles, they have a PET CT. And those that are PET-negative at that point can move to received AVD [Adriamycin, vinblastine, dacarbazine] without the bleomycin, for an additional 4 cycles. Whereas those that are PET-positive would be escalated to BEACOPP [bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine (Oncovin), procarbazine, prednisone], which is a more aggressive therapy that was primarily developed in Europe.

This is particularly attractive because it allows patients to receive a lower dose of bleomycin. The challenge, however, is that if a patient is PET-positive, escalating to BEACOPP can be a very aggressive intervention and can sometimes be challenging.

In addition to that approach, we also now have a novel combination, which includes the antibody-drug conjugate, brentuximab vedotin, which targets CD30, in combination with AVD. And this regimen is now FDA approved based on the ECHELON-1 study, which was presented at ASH [American society of Hematology] in 2017 and subsequently published in theNew England Journal of Medicine. And this was a comparison of BVAVD [brentuximab vedotin + Adriamycin, vinblastine, dacarbazine] versus ABVD for 6 cycles. And this also provides an opportunity to avoid bleomycin. What we found was that, in [the] study, there was an improvement in the modified progression-free survival. The modified progression-free survival includes those patients that progress or that die from other reasons and also includes a small number of patients that may not have progressed but had an inadequate therapy and ultimately went on to receive additional treatment. And the idea behind including that endpoint was that these were patients that had not necessarily been successfully treated with the induction regimen. So it was a goal to really be more realistic with the assessment. So these are 2 very reasonable options. At this point, I typically do not recommend ABVD for a full 6 cycles and go with one of these 2 treatment options.

Transcript edited for clarity.

A 22-Year-Old Woman With Stage IV Classical Hodgkin Lymphoma

History & Physical

• A 22-year-old female presented with right cervical nodes developing over several months
• Initially evaluated by her OB/GYN who recommended observation. She subsequently developed neck pain while drinking wine
• Referred for lymph node biopsy -> classical Hodgkin lymphoma
• Past medical history: unremarkable
• Social history: No tobacco use; occasional ETOH; Division 1 swimmer, NKDA
• Family History:
  • Maternal grandfather — Squamous cell cancer
  • Maternal grandmother — Melanoma
  • Aunt — Breast Cancer
  • 2 healthy siblings

Laboratory Values

• WBC 19.8 (85% PMN’s)
• Hgb 12.0
• Plts 571
• ESR 30
• Cr 0.76
• Albumin 4.2
• HIV/Hepatitis Negative

Staging PET/CT

• Intrathoracic adenopathy
  • R cervical 2.3 x 1.9 (SUV 9.3)
  • L cervical 2.2 x 1.8 (SUV 8.8)
  • Ant Mediastinum 4.8 x 2.9 (SUV 21.3)
  • R axillary 2.8 x 2.8 (SUV 12.2)
• Spleen SUV 2.9 with normal size
• Diffuse uptake in the axial skeleton (SUVs 4.9-5.5)
• Mediastinum SUV 1.8 / Liver 2.4

Pathology

• Nodular sclerosis classical Hodgkin Lymphoma
• Per IHC, Hodgkin cells express CD30, CD15, PAX5 (weak); negative for CD3, CD20, CD45

Treatment:A(BV)VD x 6

• Interim PET/CT with Deauville 3
• Tolerated well with GCSF support