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Boost for Seagen Hodgkin’s lymphoma drug, strong results for frontline CAR-T therapy, and more

December 11, 2023
Hello (and goodbye) from San Diego. This is Jonathan Wosen and Angus Chen reporting in our final newsletter of this year's ASH. Today, we're offering a couple highlights from the meeting as well as a look ahead at some of the late-breaking abstracts that are coming tomorrow on the last day of the meeting. Hope you enjoy these newsy tidbits as much as Jonathan enjoyed this burrito by the bay.

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Lymphoma

Seagen Hodgkin's drug works well alongside other therapies in mid-stage trial 

Antibody-drug conjugates, or ADCs, can be potent and precise cancer killers. These drugs link an antibody, which latches on to a cancer cell, with a chemotherapy drug that takes out its target. Adcetris is a perfect example. The drug, sold by Seagen, a publicly traded biotech company in Washington, combines an antibody that grabs hold of CD30, a protein found in high amounts on the surface of Hodgkin's lymphoma cells, and monomethyl auristatin E, which blocks the activity of tubulin, an essential protein that provides cells structure and support

In a pair of presentations, researchers at ASH shared updated results from an open-label mid-stage study showing that Adcetris works well as a first-line therapy for classical Hodgkin's lymphoma when paired with the checkpoint inhibitor nivolumab, which blocks PD-1, and the chemotherapy drugs doxorubicin and dacarbazine. An analysis of 154 patients with early-stage disease in the trial, dubbed SGN35-027, showed that 93% had a complete response by the end of treatment, and that 98% of these responses were maintained 12 months later. And 18 months after treatment, only 3% of patients had seen their cancer worsen.  

When researchers looked at 57 patients with advanced disease, they found that 89% had a complete response and that nearly the same fraction of those responses were maintained 24 months later. No deaths were reported in the study, and most adverse events were mild and consistent with what researchers have seen with the use of nivolumab alone.

Adcetris is already used as a treatment for CD30-containing lymphomas, and last year the drug brought in $839 million in sales for Seagen. These latest results are part of a push by the company to widen its use beyond the seven indications for which it has already been approved.


Look-AHEAD

Advances in less-buzzy bone marrow transplant for sickle cell disease

It's easy to forget amid the landmark approvals of gene therapies for sickle cell disease that there's an existing treatment that can cure patients: a bone marrow transplant. In fact, doctors know transplants have a 95% cure rate in children, and they've been doing them for decades.

But these treatments require would-be recipients to have a well-matched donor and to go through grueling chemotherapy to clear out their bone marrow stem cells, factors that have ruled out the vast majority of sickle cell patients, especially those who are older and whose organs have been ravaged by a lifetime of disease. 

Researchers at ASH will report new data tomorrow showing that sickle cell patients can safely receive blood stem cells from half-matched donors, such as a parent, child, or sibling. The mid-stage trial doesn't use the kind of heavy chemo that wipes out stem cells, instead employing a gentler regimen that prevents donor immune cells from attacking their new host. Such transplants cost about $300,000 compared to $2.2 million to $3.1 million for the new gene therapies, which, much like traditional bone marrow transplants, do wipe out a patient's blood stem cells as part of treatment. Stay tuned for a story from Jonathan tomorrow on the findings and their implications.


CAR-T

Yescarta continues to show improved outcomes as frontline therapy in three-year followup

CAR-T has steadily been crawling toward earlier lines of therapy over the last decade. Researchers working with Kite Pharma's Yescarta will present data this afternoon from the ZUMA-12 trial, the first phase 2 study testing CAR-T in frontline therapy for high-risk large B cell lymphoma. Earlier studies on Yescarta, or axi-cel, showed that the therapy was highly effective in later lines of therapy — with about half of patients achieving a complete response in the fourth-line therapy, said Frank Neumann, the global head of clinical development at Kite. 

In the first-line setting, 86% of patients had a complete response in ZUMA-12 at the three-year follow up. That confirms the hopes of oncologists who believed moving CAR-T up to earlier lines of therapy would improve outcomes for patients eligible for the treatment. "These responses are durable. What it basically tells you is for these difficult-to-treat patients, where the prognosis is bad, cell therapy Yescarta seems to be a very promising option. People around us are talking about a potential cure," Neumann said. "The earlier you treat, the better the efficacy."

Kite is now enrolling patients in ZUMA-23, which will test Yescarta in the same setting in a larger, worldwide population.



LOOK-AHEAD

Syndax's revumenib may offer leukemia patients a 'last, great chance'

Researchers from City of Hope will present pivotal Augment-101 phase 2 trial data tomorrow on Syndax's menin inhibitor, revumenib. This is one of the more highly anticipated studies on a new targeted therapy for acute leukemias with a high-risk genetic marker known as a KMT2a rearrangement. Patients with this type of leukemia have worse outcomes and, at this point, have no approved targeted therapy for it. 

In this disease, the interaction between KMT2a and the protein menin drives the leukemia and stops the differentiation of the immature leukemia cells. Menin inhibitors like revumenin block that interaction and can force the differentiation of the leukemia into "healthy, mature cells," said City of Hope hematologist-oncologist Ibrahim Aldoss. He'll present data tomorrow at ASH that will show this drug can offer patients who have already relapsed or were refractory from at least one prior line of therapy meaningful remission from their leukemia — as well as an opportunity to receive a potentially curative stem cell transplant down the line.

"This is a drug that's clearly effective among a patient population that needs this, with a manageable safety profile," said Rory Shallis, a hematologist-oncologist at Yale Cancer Center who did not work on the study. "It can serve as the last, great chance for many patients to still embark on a curative path towards transplantation."

For more details, stay tuned for a story from Angus Chen tomorrow morning.

That's all for this meeting. See you again at ASH next year – and if you're going to AACR this spring, we'll be doing another one of these newsletter round-ups. Subscribe here.


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Until next year!  

- Jonathan & Angus

Jonathan Wosen is STAT's West Coast biotech & life sciences reporter, based in his hometown of San Diego. Jonathan holds a doctorate in immunology from Stanford and a master's in science communication from the University of California, Santa Cruz. Yes, that is a lot of school. In his spare time, he enjoys jogging and following all things NBA-related.

Angus Chen is a cancer reporter at STAT. Before journalism, Angus was a geology research grunt where his primary job was smashing rocks with a very large hammer. He lives in Oakland, Calif., and enjoys surfing at gnarly Ocean Beach, San Francisco.


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