BV in Retrospect & Expected Frontline Outcomes

Jonathon B. Cohen, MD, MS:Brentuximab vedotin [BV] was one of the biggest breakthroughs in the management of Hodgkin’s lymphoma to come along when it was first developed several years ago. This is a novel approach to treating any type of cancer and was one of the first of its type to be approved for any indication. Brentuximab vedotin is an antibody drug conjugate that targets CD30 [TNFRSF8/cell membrane protein 30] and delivers a chemotherapy payload. It was initially approved for relapsed Hodgkin’s lymphoma to be used as a monotherapy.

Subsequently, it has been evaluated based on its success in the frontline relapsed setting. Following a series of studies that indicated its safety when combined with AVD [doxorubicin (Adriamycin), vinblastine, dacarbazine], there was a large, randomized clinical trial, which compared BVAVD with the standard six-cycle ABVD [Adriamycin, bleomycin, vinblastine, dacarbazine] treatment. Regardless of where a patient receives BV in the frontline, it is clearly a very active agent in Hodgkin’s lymphoma, which is a huge advancement for our field.

The consideration of BVAVD for frontline therapy is certainly a challenging decision: There have been numerous controversies regarding whether it is the most appropriate therapy at this point. One of the challenges with the clinical trial, that led to its approval, was that the comparator arm was 6 cycles of ABVD, which has lost its status as a standard of care, according to most practitioners. However, this is still an effective regimen, and I consider it for my patients who have advanced stages of Hodgkin’s lymphoma. Typically, I’ll have a discussion with the patients regarding the efficacy-to-toxicity ratio of each approach—the PET-adapted method versus BVAVD, and work with them to make the appropriate decision.

The easiest decision with regard to frontline therapy is choosing bleomycin, irrespective of the toxicity, for patients who have underlying lung disease, or those who smoke and are not able to quit. For patients [who] have underlying lung disease, poor PFTs [pulmonary function tests], smoke, or another undue risk associated with bleomycin, I will typically choose BVAVD. The other group that appears to, potentially, benefit from brentuximab vedotin, as part of the frontline approach, are those with high-risk features. Although this was a subset analysis of the larger study that was conducted, it does appear that this demographic would benefit most from the incorporation of brentuximab vedotin in the upfront setting. Otherwise, it’s an open debate regarding which approach is the most appropriate. Again, I typically will have a discussion with patents about the benefits and setbacks of each approach.

Fortunately, most patients who receive combination chemotherapy, and who achieve a complete remission, will stay in remission with potential cure. In some of these initial or prior studies regarding ABVD, the success rate was 75%. In the BVAVD study, that number is above 80%—and it is probably higher for those who have truly achieved complete remission. Although we didn’t see that in this particular case, most of my patients who achieved complete remission with standard combination therapy were or will be cured of their disease.

Transcript edited for clarity.

A 32-Year-Old Man with Stage IV Hodgkin's Lymphoma

• History & Physical:
  • A 32-year-old man presented to his PCP in January 2017 complaining of abdominal pain, pruritus, fevers of over 101⁰ F, and weight loss
• Imaging
  • PET scan showed avid mediastinal mass
• Labs
  • HgB 12.2 g/dL
  • WBC 7,500 mm²
  • ALC 3,200 mm²
  • Albumin 3.9 mg/dL
  • ANC 4,200/mm³
  • Liver and renal function tests WNL
• Biopsy confirmed mixed cellularity classical Hodgkin’s lymphoma (HL)
• Normal lung and cardiac function
• Final Staging: Stage IVB, cHL, IPS score 2
• ECOG PS 2
• He received 2 cycles of ABVD. PET/CT restaging showed Deauville (1-). He received 4 additional cycles of AVD
• He achieved a CR
• 2 years after completion of therapy, the patient complained of a persistent cough and fatigue
• PET/CT showed bilateral mediastinal masses
• Biopsy confirmed cHL