Biotech fights 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 night, Arcellx received a special waiver from ASH officials to sidestep the conference's data embargo policy so that it could issue an early press release highlighting the lack of any delayed neurotoxicity associated with its experimental treatment called anito-cel.

Arcellx timed the release to disrupt Legend's investor and analyst meeting, where the company was discussing the latest research on Carvykti, its own BCMA CAR-T therapy.

Legend has downplayed the significance of the delayed neurotoxicity — Parkinsonian symptoms and cranial nerve palsies — reported in patients receiving Carvykti, insisting it's a receding issue, especially now that Carvykti is establishing a role in treating patients with less advanced disease.

While Arcellx rushes to get anito-cel filed and approved, Legend is already a blockbuster commercial drug, establishing itself as the standard-of-care cell therapy in multiple myeloma.

On Monday, Legend CEO Ying Huang told BiotechTV, "We're not afraid of competition that may be a me-too drug."

A 'nail in the coffin' for stem cell transplants in mantle cell lymphoma

Most patients with mantle cell lymphoma seem to achieve a deep remission from modern targeted or immune therapies like BTK inhibitors or CAR-T cell therapy. That's made outcomes so much better in mantle cell lymphoma, that many oncologists have begun easing off offering autologous stem cell transplants as part of frontline treatment for many patients, wondering if such an intense and sometimes dangerous procedure was always really needed.

The results from a randomized trial presented today help to solidify the idea that transplant can be safely omitted from first line therapy if patients are already in a deep remission. "Another nail in the coffin for autologous stem cell transplant and consolidation for frontline mantle cell therapy," said Elise Chong, a hematologist-oncologist and researcher at the University of Pennsylvania who did not work on the study.

Clinicians had already begun moving away from transplants for patients that were doing well after initial therapy — typically involving chemotherapy and targeted therapy or immunotherapy — after the results of the TRIANGLE study, a different randomized trial published earlier this year in the Lancet.

The new study, presented by Timothy Fenske from the Medical College of Wisconsin, randomized patients who were MRD negative after initial therapy to either receive a transplant or just get maintenance therapy, and it found no statistical differences between the two groups. The outcome was so stark, Fenske said, that the data monitoring committee halted the trial early, "thinking it wasn't ethical to continue randomizing patients to a treatment that is toxic and may not be offering benefit."

Amgen's Blincyto improves disease-free survival in pediatric ALL

Disease-free survival improved markedly in children with acute lymphoblastic leukemia when given 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 lymphoblastic leukemia. It found that the bispecific T-cell engager improved three-year disease-free survival to a rate of 96% in patients taking it with chemo, compared to 87.9% in those receiving 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 funded in part by Amgen, and was published in the 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 might be especially beneficial for racial and ethnic groups with historically poorer outcomes, with the largest improvements seen in Hispanic children.

The takeaway? This drug combination could potentially improve outcomes in pediatric B-cell ALL, particularly by reducing bone marrow relapses in high-risk populations. However, there's no biosimilar yet for Blincyto, and it remains an extraordinarily expensive treatment.

After other CLL treatments fail, Epkinly might offer a chance for a complete remission

Eventually, no matter what therapy patients with chronic lymphocytic leukemia get, the expectation is 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 a lot of options, Danilov said.

"We are facing a new problem where patients who progress on targeted therapy — they have 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, might be able to offer another chance at remission for 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 to highlight is that this study enrolled a highly refractory group of patients," Danilov said. Many also had high-risk mutations like TP53 aberrations as well. "This is a very difficult group of patients to treat. Having a response rate of 61% with a single agent is a very significant achievement."

Brian Koffman, a retired family physician and the founder of the patient advocacy organization the CLL Society, was the first patient enrolled in this trial. He'd 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, this one will last. "I'd be lying to say I don't always hope that this will be the last therapy, no more swings at the bat," he said. "The reality is you kick the can down the road. But you hope, by the end, there's another can to kick."

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