Mono & Polytherapy Options for Relapse & Prospects

Jonathon B. Cohen, MD, MS:Patients with relapsed Hodgkin’s lymphoma need to be evaluated on an individual basis. Fortunately, we still have curative options for patients [who] do relapse. In our designated case, for example, the patient relapsed a few years after completing [his] initial therapy and, being in his mid-30s, is an optimal candidate for aggressive therapy. One of the considerations is to treat patients with an autologous stem-cell transplant—a curative approach with a 50% success rate. If I have a patient [who] is otherwise young and does not have other comorbidities or complications, I typically consider a second-line chemotherapy with a regimen such as ICE [ifosfamide, carboplatin, etoposide]. If there is a good response to the therapy, I then proceed with autologous stem-cell transplant.

In some instances, for patients [who] have particularly high-risk features at relapse, we will do a stem-cell transplant and then proceed with brentuximab vedotin [BV] as maintenance, which is, by the way, an FDA indication. That’s something I often consider for patients [who] either relapse early or have extranodal disease at relapse—or who may not have a complete remission going into their transplant.

Brentuximab vedotin, which was first developed for the relapsed setting, may be administered to such patients in a variety of ways: the most straightforward indication is for those relapsed patients who are not transplant-eligible, especially after receiving 1 salvage therapy prior to the brentuximab vedotin; the other indication concerns patients who receive a stem cell transplant and thereafter progress. In both circumstances, BV is very effective.

Fortunately, for patients with relapsed Hodgkin’s lymphoma, we now have a variety of treatment approaches. We’ve discussed the potential role of stem-cell transplants and considered the use of brentuximab vedotin either in conjunction with a transplant or as a monotherapy. Additionally, there are multiple combination treatments containing BV that are under investigation. One other class of agents, though, that is particularly exciting are the PD-1 antibodies nivolumab and pembrolizumab: These are checkpoint inhibitors that stimulate the immune system and attack the underlying Hodgkin’s lymphoma. We found that roughly two-thirds of patients with relapsed HL will respond—typically with durability—to these PD-1 antibodies. This is certainly an effective consideration, especially in a patient who may have underlying neuropathy or for whom I’m concerned that bentuximab vedotin may not be a good option. Moreover, nivolumab is currently being investigated, in the frontline setting but also in the relapsed setting, in combination with brentuximab vedotin. These 2 agents may, in the future, be administered together for patients with relapsed disease.

Now that we have multiple effective treatment options and have started to move beyond standard ABVD [doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine], there are a variety of challenges with regard to which therapies patients should receive, and when. I typically address this on an individual basis with consideration of their risk factors and comorbidities. In a patient [who] ultimately chooses to receive ABVD as a PET [positron emission tomography]—directed approach and relapses after a period of complete remission, I often urge them to accept a transplant. However, if they are unwilling or unable, my first option is typically brentuximab vedotin. Again, this is still a personal decision based on the patient’s individual risk factors. I’m still excited, though, about the clinical trials that are currently investigating this combination therapy, because I suspect it may have increased efficacy as opposed to separate administrations. We’ll have to wait and see when those studies come out.

In this particular case, we had a young patient who was given aggressive therapy, achieved a complete remission, and who, unfortunately, continued to progress; we need to, in the realm of research, rigorously pursue the identification of high-risk patients so things like this do not happen. We have several laboratories and clinical factors that have been retroactive for 15 to 20 years, which we can use—but there’s more that we can do to understand the underlying biology of Hodgkin’s lymphoma, to increase the chances of relapse prevention.

I’m also excited to learn more about the role of combination therapies, both in the upfront and relapsed setting—and, hopefully one day, we will have a better understanding of frontline regimens to optimize treatment. I know there are additional studies that are being planned that may help us, ultimately, to answer this question.

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