Newer Treatment Options for Patients With Relapsed Hodgkin Lymphoma

Stephen Ansell, MD, PhD, Chair, Lymphoma Group, Mayo Clinic, Rochester, Minnesota, discusses newer therapy options for treating patients with relapsed Hodgkin lymphoma. This information was presented at the 2019 ASH Meeting on Hematologic Malignancies.




Hi, my name is Stephen Ansell, I am the chair of the lymphoma group at Mayo Clinic in Rochester, Minnesota. At the recent ASH Meeting on Hematological Malignancies I focused on newer options in patients with relapsed Hodgkin's lymphoma.

While Hodgkin's lymphoma may have a very good outcome overall, if with initial therapy be it chemotherapy or chemotherapy combined with radiation therapy, there is still a subset of patients who progress after treatment. Our goal is obviously to see that those patients have a good outcome and can be salvaged with appropriate treatment.

The exciting news in recent years has been new agents that have been found to be effective in patients with Hodgkin's lymphoma, specifically these agents are targeted CD30 in the way of brentuximab vedotin, or targeting PD‑1 in the way nivolumab, pembrolizumab, and other anti‑PD‑1 antibodies.

These have been tested in relapsed patients, but now are being used as first salvage therapy, so recent data has shown that the use of brentuximab vedotin and PD‑1 blockage together as the first treatment prior to an autologous stem cell transplant, has very high response rates.

These response rates are very similar to what is obtained with chemotherapy, and in a study published this past year, a subset of 62 patients were analyzed and in fact, the complete response rate was seen in 61% of patients.

This is a very promising and is a very good alternative to standard chemotherapy. The first exciting piece of news was these new agents are now being used as initial salvage therapy. A second piece of new information that is very exciting is the use of new agents as consolidation after an autologous stem cell transplant.

The use of brentuximab vedotin as consolidation treatment has been tested in a trial called the AETHERA trial, and this trial specifically looked at high‑risk patients and tested whether brentuximab vedotin compared to a placebo improved the progression‑free survival. In fact, this has been documented to be a very successful strategy and is now a standard approach.

The exciting news is now there is a study using a PD‑1 blocking antibody in a very similar population of patients post‑transplant, also showing that it improves the progression‑free survival. As we look to the future, the exciting next thing is to see whether either 1 or the other or even a combination may improve outcomes after transplant.

The third exciting information is that additional new anti‑PD‑1 and even anti‑PDL‑1 antibodies are now being tested in patients with relapsed Hodgkin's lymphoma. At this time, nivolumab and pembrolizumab are both approved for patients with this situation of relapsed disease.

There are data targeting PD‑L1 with an antibody called avelumab, and subsequently 2 additional anti‑PD-1 antibodies which are called sintilimab, and atezolizumab, both of which have shown very encouraging results.

I think both of these agents have also shown high complete response rates, so I think these are agents to watch with very promising results in patients that have failed an autologous transplant and have failed brentuximab vedotin.

Then a final point that I thought was important to make, and that is well what about folks that have failed all of these exciting agents, the brentuximab vedotin and the PD‑1 blocking antibodies, what's in their future? What are potential other options?

I think there are 2 other options that are really something to watch. The first is the use of CAR‑T cell (chimeric antigen receptor T‑cells), just as has been tested in B‑cell lymphomas, now in Hodgkin lymphoma targeting CD30 rather than targeting CD19, we have now seen in small numbers of patients quite promising results.

At the recent ASH meeting in December last year, 2 trials were reported and in both of these, the complete response rate looked very promising and a number of patients have had very durable benefit.

Obviously, this will need to be validated in a larger percentage and a larger cohort of patients, but I think just as this has been very promising in aggressive B‑cell lymphomas, our hope is that this will be very promising for Hodgkin's patients.

Finally, CD25 antibody drug conjugates, so in other words, an antibody with a chemical attached to the back which would poison the cells that it binds to, have been very promising, and in fact brentuximab vedotin is such an antibody drug conjugate.

There is a new antibody drug conjugate which is called ADCT301, and it is targeting CD25 with a PBD dimer at the back. This has had very good success so far in Hodgkin's lymphoma, an overall response rate of over 70%, with a complete response rate of about 45%.

Promising future agents for patients with relapsed Hodgkin's lymphoma are both CAR‑T cell therapy and new antibody drug conjugates.

All told, much though we would love to see patients cured with the first therapy, even for patients where this is disease recurrence, multiple therapies are proving very promising and outcomes have been good.

Our goal obviously as we look to the future is to use these agents either on their own or in combination to not only improve outcome of patients but in fact cure them. That's really where we're hoping to see things go.


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