Current Treatment Landscape for Patients With Relapsed/Refractory Hodgkin Lymphoma

At the 2023 Great Debates & Updates in Hematologic Malignancies meeting in Boston, Massachusetts, Andrew Evens, DO, MBA, MSc, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, discusses the current treatment options for patients with Hodgkin lymphoma after relapse occurs, including but not limited to checkpoint inhibitors, autologous stem cell transplantation plus salvage therapy, and CAR T-cell therapy. 

Transcript: 

Hi. My name is Dr. Andy Evans at the Rutgers Cancer Institute of New Jersey. I'm happy to be at Great Debates and Updates in Hematologic Malignancies in Boston, Massachusetts. I'd like to talk about the treatment landscape of relapsed refractory (R/R) Hodgkin lymphoma. Suffice it to say, especially bookend with the discussion I was mentioning a little bit ago about newly diagnosed advanced-stage Hodgkin lymphoma, that landscape is actively changing. 

What do I mean by that? For most of us in the field, and really in the community for that matter, a very common treatment, if not standard of care, has been brentuximab vedotin, or Adcetris, plus [doxorubicin, vinblastine, and dacarbazine] (AVD). Certainly, since the overall survival data broke through last year. It has been my standard practice for multiple years, really since its FDA approval, or especially once we saw that 3-year update that the [progression-free survival] (PFS) looked to be mature and was holding through. With that as a frontline treatment, I would say with a first relapse, if someone had received [an] AVD in the frontline setting, many of us would then be incorporating checkpoint inhibitor to first salvage, and that's number 1.

Number 2, for younger patients, it really is a salvage regimen as a bridge to an autologous stem cell transplant. That has been for the last several years, the paradigm. There's not one right regimen for that first salvage. One of the more common ones being used is pembrolizumab with [gemcitabine, vinorelbine, and pegylated liposomal doxorubicin] (GVD) chemotherapy. Dr. Moskowitz [Alison J. Moskowitz, MD, Memorial Sloan Kettering Cancer Center, New York, New York] had published that in a single institution series that is very active, although some toxicities have to be navigated such as mucositis and rash, etc., but [it has a] very high [complete response] (CR) rates.

There are other regimens or even chemo-free regimens or chemo-light regimens—meaning, Dr. Diefenbach [Catherine S. Diefenbach, MD, Perlmutter Cancer Center, New York, New York] had published a study, or early part of a study, looking at brentuximab vedotin and nivolumab without chemotherapy. Others had even done single-agent brentuximab vedotin as a bridge to an autologous stem cell transplant (ASCT). That's 1 part to it that we have to navigate. Part 2 to it is you do your salvage, [and] hopefully they go into a complete remission [and] have a successful stem cell transplant. 

What about maintenance brentuximab vedotin? We know that's FDA-approved for certain risk groups of patients, and we typically have done that. Obviously, we need to follow closely for neuropathy and other tolerability, and then hopefully they're cured.

Now, can patients still relapse? It can happen, of course. Thankfully, it's not common. If you've relapsed after brentuximab vedotin and after a checkpoint inhibitor, it does get a little challenging, I will say. You can certainly use other chemotherapy agents. Thankfully, there are some new agents making their way through. CAR T against CD30 is much earlier than, of course, CD19 and B-cell lymphomas. But, that and other targeted [therapies]—there's other immunotherapy and different checkpoints being looked at in relapsed/refractory Hodgkin [lymphoma]. 

The real challenge is if the field will be changing in the next several months or 1 to 2 years. We are now using checkpoints [as] frontline, such as nivo-AVD, as I had discussed in the 1826 study, we're going to have to reassess. 

Now, is it someone relapsing years later where you would be comfortable reusing a checkpoint? I think if it's someone who's relapsing within 3 to 6 months, we'll probably not want to reuse a checkpoint inhibitor.

If we didn't use a frontline, brentuximab vedotin would come back. There were a decent amount before we had frontline brentuximab vedotin where we used it in the salvage, whether, as I alluded, to single-agent [or] even combination. Dr. LaCasce [Ann S. LaCasce, MD, MMSc, Dana-Farber, Boston, Massachussets] published brentuximab vedotin with bendamustine [which] we had used for quite a while. I think that will kind of re-anchor its place in the second-line setting if it gets bumped out of the frontline setting. Then we'll have to figure out downstream of that. I'll say [treatments are] actively changing, although we certainly have semi-standard or common paradigms that we use for this setting.

The last thing I will mention on relapsed/refractory [cases] is older patients. Not everybody can go to an autologous stem cell transplant, and so it usually [there] is some adaptation of: can they receive chemotherapy? Is it just novel agents? How long do I give that novel agent if they're not going to a transplant, whether it's brentuximab vedotin, or checkpoint inhibitor is unknown? Usually, it's treat-until-progression and tolerability. Sometimes we'll take a break after some time. But, that's another active area that needs to be studied.

Source: 

Evens A. Antibody Drug Conjugates – Where and When to Use Them in Hodgkin Lymphoma. Presented at the Great Debates and Updates in Hematologic Malignancies Meeting; August 17-19; Boston, Massachusetts.