Frontline CD30 ADC for Advanced Classical Hodgkin Lymphoma - Episode 4

Considerations for Treating With Brentuximab Vedotin

June 26, 2019

Siddhartha Ganguly, MD, FACP:We use brentuximab vedotin in different scenarios. Because it is a transplanter, the most common indication are patients with high risk of relapse who underwent autologous stem cell transplantation to use brentuximab vedotin single agent every 3 weeks for 1 year as a consolidation and maintenance strategy, which was shown in the AETHERA trial to be superior in improving progression-free survival compared with placebo. That is 1 of the most common indications that I use in my practice. I also recommend using A-AVD [Adcetris, doxorubicin, vinblastine, dacarbazine] in the populations where I think patients will benefit.

And I have seen brentuximab vedotin having toxicities that are quite manageable. Again, as a transplanter, I like to take my patients to the transplant, if possible, in a PET [positron emission tomography]—negative status. Hence, if somebody relapses after ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine] and [is] still PET-positive prior to the transplantation, I often used brentuximab vedotin to make them PET-negative and then take them to the autologous transplant. And then I put them on the brentuximab vedotin maintenance and consolidation for 1 year. And I’m seeing pretty good results with this type of combination treatment.

One has to be careful about the toxicities and adverse events in this type of approach. Brentuximab vedotin is known to cause peripheral neuropathy. And in the ECHELON trial, almost two-thirds of the patients developed some form of peripheral neuropathy. The good news is that in grade 3 or 4, that means advanced cases of peripheral neuropathy were not very common. I think that incidence was in the figure of teens, like 11%, 12%, 13%. The good news is that of those patients who developed peripheral neuropathy, almost two-thirds of them completely resolved their peripheral neuropathy over several months after stopping the therapy. Hence, it is very important to counsel the patients before starting brentuximab vedotin.

What we do in our practice, first of all, I thank all our nurses because they are at the forefront. They identify those early symptoms. Often, our nurses are really excellent in identifying if someone was enjoying crocheting and now cannot do the finer movements, cannot button the shirt, or cannot pick up a dime that dropped on the floor. And those are early, subtle signs of peripheral neuropathy.

Vigilance, early diagnosis, and then based on that, dose adjustments, or dose reductions, or dose delays. By doing that, we often either halt or prevent further progression of peripheral neuropathy. And then after the end of the therapy, we have seen almost two-thirds of the patients completely resolve and rest, almost half of them improve more than 50% of their symptomatology. Unfortunately, 10% to 15% of the patients are left with peripheral neuropathy at the end of the therapy and hence, again, identifying them right in the beginning and being vigilant is the main important step for any oncologist treating patients with brentuximab vedotin.

Dr Galal, could you please let us know when you use brentuximab vedotin in your own patients? And give examples for some patients who you consider their use.

Ahmed Galal, MD, FRACP, MSc:I do use brentuximab vedotin quite frequently in my own patients in different situations. The first 1 is the classical Hodgkin lymphoma, where it’s indicated in the frontline therapy for higher-stage Hodgkin lymphoma, so stage III or IV. These patients benefit a lot from a combination of brentuximab vedotin and the chemotherapy. Their outcome is very good, and by using the growth factors like Neulasta or G-CSF [granulocyte colony-stimulating factor], we come around the risk of febrile neutropenia and neutropenia in general. The peripheral neuropathy is very well tolerated in general and reversible. Even for the patients who have irreversible type of peripheral neuropathy, they do have a lower grade eventually from that peripheral neuropathy. I do use it in that kind of population, also in the peripheral T-cell lymphoma and cutaneous T-cell lymphoma. As a matter of fact, I do have a big population of cutaneous T-cell lymphoma being treated in my clinic, and I use brentuximab vedotin very often once they have CD30 positivity.

In the classical Hodgkin population, I’ve seen very good response rates judged by the PET2 negativity. I can tell you that 99% of my patients actually had a negative PET scan after the second cycle, presenting with very advanced disease and bulky disease as well.

Most of my patients in that kind of category, so far, were a younger population. They tolerated the combination very well without any admission for febrile neutropenia, and they do receive the growth factors effectively. I have seen really very positive outcomes from that population. Haven’t had any patients who have been relapsed as of yet. However, we monitor them very closely for that.

In proliferative T-cell lymphoma, I’ve seen very good response rates, especially in the anaplastic large-cell lymphoma. The question with the longer follow-up is, how durable is that in this kind of category of patients? Because it is a tough disease to treat.

Other than that, the good response rate and changing our approach to treating these kinds of diseases, the adverse effects are very known and we’re quite aware of it, and we manage it very well. We can reduce the doses based on the degree of their peripheral neuropathy and based on the kidney or liver function. We’re quite educated about it, and we know we can expect the adverse effects and deal with it. We don’t tend to delay any therapy, especially in the Hodgkin lymphoma patient.

I think brentuximab vedotin did change the approach to the frontline therapy for advanced-stage Hodgkin lymphoma. Based on the ECHELON-1 trial results showing the modified progression-free survival advantageous in favor of the A-AVD and showing that reduction of risk by 23% of death or progression. And this was reinforced by the 3-year data discussed at ASCO [the American Society of Clinical Oncology Annual Meeting] this year, and not the American experience that showed that the modified progression-free survival and the progression-free survival both are in favor of the A-AVD.

I mentioned in the frontline therapy—but also in the relapsed-refractory—the use of bendamustine, brentuximab, or the bendamustine plus nivolumab or any other checkpoint inhibitor has opened the door to more treatment and better responses, and it might get the patients to transplant, to be fit for transplant, or even having durable responses if they don’t fit for the transplant with a frequent follow-up.

Transcript edited for clarity.