Frontline BVAVD in Classical Hodgkin Lymphoma

Jonathon B. Cohen, MD, MS:Brentuximab vedotin [BV] is an antibody-drug conjugate that targets CD30 and was really a remarkable achievement when it was initially developed several years ago. Up until this time, we had had combination chemotherapy and could consider an autologous transplant for patients with relapsed disease. But for those who progressed after an autologous transplant or for whom transplant was not an option, we had very limited options and often relied on chemotherapy-based combinations, including gemcitabine and such.

Brentuximab vedotin has a very high overall response rate as a single agent in the relapsed setting. And so for several years now, we’ve been using it and it’s markedly changed the outlook for patients with relapsed disease.

I was excited to see it being evaluated in a number of other settings, including in the post—auto transplant setting as consolidation. This is particularly effective for patients [who] have high-risk disease, including those [who] relapse early or may have extra nodal sites of disease. I often will offer brentuximab vedotin to those patients as soon as they finish their autologous transplants. And now we obviously have the opportunity to use brentuximab vedotin in the frontline setting in combination with AVD [doxorubicin (Adriamycin), vinblastine (Oncovin), and dacarbazine]. So it really has revolutionized the management of patients with classical Hodgkin lymphoma.

So we fortunately now have an FDA approval for patients to receive brentuximab vedotin in the frontline setting in combination with AVD. And this was based on the ECHELON-1 study that was published earlier this year in the [New England Journal of Medicine]. And what they found in this study was that there was a statistically significant improvement in the modified progression-free survival when compared to ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine] for 6 cycles. Over the last 12 to 18 months, we’ve now had additional data published or presented, which has identified some longer-term follow-up, and we continue to see this benefit for patients. In addition, we’ve now had a chance to look at additional endpoints, such as this more standard progression-free survival, and we continue to see a benefit for patients over ABVD for 6 cycles.

So the case that we described today was a 22-year-old healthy female with no significant past medical history who had advance-stage Hodgkin lymphoma. And I think BVAVD [brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine] is a very reasonable option for a patient in that situation. I think you could certainly consider other options, including a PET-adapted approach. I think both are very reasonable. But I often will choose BVAVD based on the improvement in modified, and now standard, progression-free survival.

I often think about frontline BV in most of my patients with advanced-stage Hodgkin lymphoma. I think it is especially important to consider in patients that have an underlying lung toxicity or some other pulmonary condition that would put them at risk to receive bleomycin. I think that’s probably the group that I feel the strongest about receiving BV as opposed to ABVD. In addition, though, those patients that have high-risk features—again, including extra nodal disease, anemia, low albumin and other features that make up the international prognostic score—those patients I think may especially benefit from intensification to receive BVAVD.

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