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This summary of news from the ASH 2024 conference first appeared in STAT’s “ASH in 30” newsletter.
Is it Tuesday yet? This is the last day of the American Society of Hematology meeting. Thanks for stopping by to read all our coverage. San Diego has been a great host city and we look forward to being in Orlando next December.
Biotech battles are very entertaining
The feud between Arcellx and Legend Biotech over their anti-BCMA CAR-T therapies for multiple myeloma is getting extra spicy.
On Sunday evening, Arcellx received a special waiver from ASH officials to bypass the conference’s data embargo policy so it could issue an early press release highlighting the lack of any delayed neurotoxicity associated with the experimental treatment called anito-cel.
Arcellx timed the release to disrupt Legend’s investor and analyst meeting, where the company discussed the latest research into Carvykti, its proprietary BCMA CAR-T therapy.
The legend downplays the significance of the delayed neurotoxicity – Parkinson’s symptoms and cranial nerve palsies – reported in patients receiving Carvykti, emphasizing that it is a declining problem, especially as Carvykti begins to play a role in treating patients with less advanced disease .
While Arcellx races to get anito-cel filed and approved, Legend is already a successful commercial drug, establishing itself as the standard cell therapy in multiple myeloma.
On Monday, Legend CEO Ying Huang told BiotechTV: “We are not afraid of competition that might be a me-too drug.”
A ‘nail in the coffin’ for stem cell transplants for mantle cell lymphoma
Most patients with mantle cell lymphoma appear to achieve deep remission with modern targeted or immunotherapies such as BTK inhibitors or CAR T-cell therapy. That has improved outcomes in mantle cell lymphoma so much that many oncologists have begun to relax offering autologous stem cell transplants as part of first-line treatment for many patients, questioning whether such an intense and sometimes dangerous procedure is always really necessary. was.
The results of a randomized trial help strengthen the idea that a transplant can be safely omitted from first-line therapy if patients are already in deep remission. “Another nail in the coffin for autologous stem cell transplantation and consolidation for first-line mantle cell therapy,” said Elise Chong, a hematologist-oncologist and researcher at the University of Pennsylvania who did not participate in the study.
Doctors had already begun moving away from transplants for patients who did well after initial therapy — usually with chemotherapy and targeted therapy or immunotherapy — after the results of the TRIANGLE trial, another randomized trial that was published earlier this year in the Lancet was published.
The new study, presented by Timothy Fenske of the Medical College of Wisconsin, randomized patients who were MRD negative after initial therapy to either receive a transplant or simply receive maintenance therapy, and found no statistical differences between the two groups . The outcome was so grim, Fenske said, that the data monitoring committee stopped the study early, “under the impression that it was not ethical to continue randomizing patients to a treatment that is toxic and may not provide benefit.”
Read more.
Amgen’s Blincyto improves disease-free survival in children with ALL
Disease-free survival improved significantly in children with acute lymphocytic leukemia when they received blinatumomab – marketed by Amgen as Blincyto – in addition to a standard chemotherapy regimen.
The study enrolled 1,440 children with newly diagnosed standard-risk B-cell acute lymphocytic leukemia. It showed that the bispecific T-cell engager improved three-year disease-free survival to 96% in patients who used it along with chemotherapy, compared with 87.9% in those who received chemotherapy alone.
Blinatumomab was first approved by the Food and Drug Administration in 2014 and was the first bispecific antibody drug to hit the market. The trial was partially funded by Amgen and was published in the newspaper New England Journal of Medicine.
Adding blinatumomab increased the risk of sepsis and catheter-related infections in some patients, but there were no treatment-related deaths in the study. The authors noted that this regimen could be especially beneficial for racial and ethnic groups with historically poorer outcomes, with the greatest improvements observed in Hispanic children.
The takeaway? This drug combination could potentially improve outcomes in pediatric B-cell ALL, especially by reducing bone marrow relapse in high-risk populations. However, there is no biosimilar for Blincyto yet, and it remains a biosimilar extremely expensive treatment.
After other CLL treatments fail, Epkinly may offer a chance for a complete remission
No matter what therapy patients with chronic lymphocytic leukemia receive, the expectation is ultimately that they will relapse if they live long enough, Alexey Danilov, a hematologist-oncologist and cancer researcher at City of Hope, said in an interview. After BTK inhibitors like ibrutinib or CAR-T therapy like liso-cel, patients currently don’t have many options, Danilov said.
“We are facing a new problem where patients progressing with targeted therapy has become an unmet need,” he said.
That’s why Danilov and his colleagues began testing whether Abbvie’s Epkinly, a bispecific T-cell engager also called epcoritimab, could potentially offer a new chance at remission to relapsed or refractory patients with CLL. In a small phase 1/2 trial presented at ASH, Danilov showed that 61% of 23 patients responded to the drug and 39% had a complete response.
“The feature that should be emphasized is that this study included a very insensitive group of patients,” Danilov said. Many also had high-risk mutations such as TP53 abnormalities. “This is a very difficult group of patients to treat. Having a 61% response rate from one agent is a very significant achievement.”
Brian Koffman, a retired general practitioner and founder of the patient organization CLL Society, was the first patient to participate in this study. He had previously had good responses to targeted therapy and CAR-T therapy, but, like many other CLL patients, eventually relapsed.
Koffman is one of the patients who experienced a complete response. Hopefully, he said, it will last. “I’d be lying if I said I didn’t always hope this would be the last therapy, no more bats,” he said. “The reality is you kick the can down the road. But you hope there’s still a can to kick by the end.