Updates on Trials of Zilovertamab and Brentuximab Vedotin in Lymphomas With Hun Lee, MD

At the recent American Society of Hematology (ASH) Annual Meeting, Oncology Data Advisor met with Dr. Hun Lee of MD Anderson to discuss the two abstracts that he presented there. Dr. Lee provided an update on the promising data for zilovertamab plus ibrutinib for patients with mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and chronic lymphocytic leukemia (CLL), and for brentuximab vedotin plus nivolumab and chemotherapy for patients with Hodgkin lymphoma.  

This podcast episode was recorded live by Oncology Data Advisor and ConveyMED at the 2022 ASH Annual Meeting in New Orleans.

Oncology Data Advisor: Welcome to Oncology Data Advisor. Today, we’re here at the ASH Annual meeting, and I’m here with Dr. Lee from MD Anderson. Thanks so much for being here.

Hun Lee, MD: Thank you so much for this invitation, Keira.

Oncology Data Advisor: Would you like to tell us about yourself and your research?

Dr. Lee: My name is Hun. I am an Associate Professor at MD Anderson. I am part of the Rare Lymphoma Team led by Dr. Michael Wang. I lead the Classical Hodgkin Lymphoma Section of the Rare Lymphoma Team. And we’re here now in the Big Easy, in New Orleans, and we’re happy to be here to present our awesome data to everybody. Hoping to help all our patients is our goal.

Oncology Data Advisor: So, I know you have two abstracts here, and the first one is about zilovertamab for CLL, MCL, and MZL. Would you like to tell us about this one?

Dr. Lee: Yes, we’re very excited about this abstract of zilovertamab (zilo) plus ibrutinib for relapsed/refractory MCL, CLL, and MZL. As you know, mantle cell is a very rare subtype of lymphoid malignancy, which is one of the rare lymphomas. Fortunately, we have many treatment options, and we’re proposing an additional option that has seemed to have very great efficacy and, at the same time, a tremendous safety profile. Many patients in the elder population especially seem to benefit well. In the CLL and MZL population, we’re getting the data, but really, the mantle cell portion of this zilo plus ibrutinib study was very exciting.

As you know, ibrutinib has been a superstar for, probably, the past decade. Single-agent activity has been very, very good, but we want to do even better. We want to partner it with an antibody that can improve the outcomes of this population without increasing the toxicity. And that’s what we have with zilo plus ibrutinib. We have seen great tolerability. The toxicity rate did not increase because of the addition of the zilovertamab. The efficacy doubled in terms of the complete remission rates, and there was about a 20% overall response rate, so we are very encouraged.

In the CLL arm, we also saw some very interesting data, especially in the tumor protein 53 (TP53)–altered, high-risk patients. They seem to do tremendously well. However, the numbers were small, so obviously we need to be realistic and say, “Hey, we need to do a bigger study in order to see whether this signal is real?” We’re still currently enrolling marginal zone lymphomas for zilo plus ibrutinib. So, if you have any interest, please reach out to me at hunlee@mdanderson.org, and we’ll be more than happy to discuss with you about the trial.

Oncology Data Advisor: Awesome, that’s very exciting. So, your other abstract on brentuximab in Hodgkin lymphoma, would you tell us about this one as well?

Dr. Lee: Yes. The second abstract is about a completely different histology. We’re talking about classical Hodgkin lymphoma, which is the most common lymphoid malignancy in the under-40 population, whereas mantle cell and CLL are mostly over 65. I’m not saying that they’re only in the less-young population, but for Hodgkin’s lymphoma, the median age in our trial was 35, so you can see the population.

The standard of care has been ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) since Bill Clinton was President, so we’re trying to improve. Yes, there has been the ECHELON-1 study of brentuximab plus AVD (doxorubicin/vinblastine/dacarbazine), which has had six-year follow-up showing overall survival benefits. It’s great, but well, what’s next? We’re trying to get what’s next. Can we do better than ECHELON-1? In North America—and I won’t talk about the controversy between escalated BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone) and ABVD—but in North America, ABVD has been one of the standards, and we wanted to improve on ECHELON-1.

Therefore, one of the key elements in the past five years has been the checkpoint inhibitors. Hodgkin is probably the only lymphoid malignancy that really responds to checkpoint inhibition, and we have had great success. Therefore, we wanted to incorporate one of the most active agents to frontline treatment, along with the key ingredients such as brentuximab vedotin, and then try to omit some of these less-young chemotherapeutic agents that have caused us lots of problems. Bleomycin is the pulmonary toxicity has been omitted. Now the vinblastine, which was one of the other agents in question, has been dropped off. The mechanism of action of brentuximab and vinblastine has been very similar, so we didn’t want to double up on the same mechanism of action.

So, now you have a very mechanistic, logistical, logical regimen of brentuximab, nivolumab, and the AD (doxorubicin/dacarbazine) chemotherapy backbone that we felt would aid our patient population. And so far, we have done that. Last year, we presented as a poster presentation with an overall response rate of 93% and a complete remission rate of 88%. So far, with the longer 17-month follow-up, we’re still showing tremendous progression-free survival (PFS) at close to 95%, estimated at 12 months.

But obviously, there’s no such thing as a free lunch. If you add all these together, what is the price, meaning the toxicity? With the programmed cell death protein 1 (PD-1) inhibitor, we do have what’s known as immune-mediated toxicities that are not seen in ABVD. However, we did not see an increase when we combined it with the brentuximab and the AD. We did not see an increase in immune-mediated toxicity as we would’ve seen for the FDA-approved indication, which is single-agent nivolumab in the third line or beyond after auto transplant.

We’re trying to get closer and closer to the best, until we get to 100%. And that, I think, is feasible—maybe not in my lifetime, but in the future, we’re trying to get to that 100% of curing everyone.

So, we were very pleased. We did not increase any toxicity, but we feel that we have increased the efficacy and the cure rates. That’s with an asterisk; obviously it takes a little time. The five-year follow up is not there yet; this is the median follow-up of 17 months, but we’re very excited. Obviously, there’s great excitement around this. Hodgkin is one of these lymphomas that is highly curable, and our young population deserves the best. We’re trying to get closer and closer to the best, until we get to 100%. And that, I think, is feasible—maybe not in my lifetime, but in the future, we’re trying to get to that 100% of curing everyone.

Oncology Data Advisor: Absolutely, that’s so exciting. Thank you so much for sharing this.

Dr. Lee: Thank you so much, and we’ll see you around ASH.

Thank you for listening to this podcast, recorded live at the 2022 ASH Annual Meeting by Oncology Data Advisor and ConveyMED. For more expert perspectives on the latest in cancer research and treatment, be sure to subscribe to the podcast at conveymed.io and OncData.com. Don’t forget to follow us on social media for news, exclusive interviews, and more.

About Dr. Lee

Hun Lee, MD, is an Associate Professor in the Department of Lymphoma/Myeloma and the Jessica and Jeffrey Brue Endowed Professor of Lymphoma Research at The University of Texas MD Anderson Cancer Center. His research focuses on the development of novel targeted treatments and combinations for mantle cell lymphoma and Hodgkin lymphoma.

For More Information

Lee HJ, Choi MY, Siddiqi T, et al (2022). Phase 1/2 study of zilovertamab and ibrutinib in mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), or marginal zone lymphoma (MZL). 64th American Society of Hematology Annual Meeting. Abstract 232.

Lee H, Flinn IW, Melear J, et al (2022). Brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine (AN+AD) for advanced stage classic Hodgkin lymphoma: updated efficacy and safety results from the single-arm phase 2 study (SGN35-027) (part B). 64th American Society of Hematology Annual Meeting. Abstract 314.

Transcript edited for clarity. Any views expressed above are the speaker’s own and do not necessarily reflect those of Oncology Data Advisor. 

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