The American Society of Hematology’s annual meeting continued Monday with important presentations and discussions on the latest blood disease research, several of which we’ve summarized here.
Sequencing BTK inhibitors in leukemia
In the years since the approval of Imbruvica for chronic lymphocytic leukemia a decade ago, it and other so-called BTK inhibitors have become mainstay treatments for the slow-growing blood cancer. Their adoption has given physicians new options to control the disease’s progression, but also new questions around how they might combine and sequence the therapies.
This year’s ASH meeting could give doctors some needed answers, featuring two important studies involving Calquence, a BTK blocker from AstraZeneca, and Jaypirca, a similarly targeted drug from Eli Lilly that works in a slightly different way.
Lilly’s study of Jaypirca is the first randomized Phase 3 trial in CLL that’s exclusively enrolled patients who previously were treated with another BTK inhibitor. “This was a clinical trial that really represents the patient population that … has received these modern standards of care over the past few years and now needs something else,” said David Hyman, Lilly’s chief medical officer, in an interview.
Results showed Jaypirca nearly doubled the time to disease progression or death compared to investigator’s choice of two older drug regimens. Jaypirca also substantially lengthened the median time to next treatment or death by 13 months over the control group. Treatment with Lilly’s drug led to fewer severe side effects, too.
According to Jacob Van Naarden, head of Lilly Oncology, the data raise the question of whether physicians might want to try Jaypirca instead of another drug called Venclexta after a patient’s disease progresses on their first BTK inhibitor. (Venclexta targets a different protein than BTK.)
Jaypirca was approved in the U.S. one year ago for adults with CLL who have received at least two lines of prior therapy. Lilly plans to submit this new data to regulators as confirmatory evidence for that accelerated approval.
Also at ASH, AstraZeneca presented results from a study combining its drug Calquence with Venclexta in previously untreated CLL patients. The combination reduced the risk of disease progression or death by 35% versus standard chemoimmunotherapy, according to the data. Adding a third, different drug, Gazyva, lowered the risk even further, but at the cost of a higher rate of side effects.
“With these more recent therapies, people with CLL can live a pretty long time,” said Van Naarden. “And so the question is: How do you get the most total amount of disease control over the course of the person’s life? Do you get more out of using [these drugs] upfront together versus in sequence?”
Questions, but few answers, on sickle cell drug recall
At many of ASH’s recent meetings, attendees have heard of progress in the development of new drugs for sickle cell disease, work that led to four new approved medicines over the past five years.
Conference-goers this year had a different sort of news to process. Just over two months ago, Pfizer abruptly withdrew one of those new medicines from markets worldwide, citing new safety concerns that, in its view, meant the drug’s benefits no longer outweighed its risks.
In particular, emerging data from several studies showed an imbalance in deaths, mostly from malaria infections, among participants on Pfizer’s drug. Observational testing, meanwhile, found higher rates of sickle cell pain crises after treatment.
“I think [Pfizer’s decision] took many of us — many of the people I know by surprise,” said John Strouse, a hematologist and sickle cell specialist at Duke University, during a special ASH session on Pfizer’s withdrawal of its drug, called Oxbryta.
Strouse ran a poll of the audience during the session, asking for the reactions doctors and researchers had had. Two-thirds chose “surprise,” 11% picked “angry” and 7% “anxiety.”
While there had been signs of growing questions around Oxbryta’s safety, Strouse and other speakers at the ASH session noted they had heard little from Pfizer prior to the withdrawal.
“We need to encourage timely public disclosure of scientific findings to allow for vigorous conversation,” said Alexis Thompson, chief of the Children’s Hospital of Pennsylvania’s hematology division. “I think it’s safe to say that didn’t happen here.”
Strouse recounted some of the difficulties sickle cell physicians encountered in responding to the withdrawal, including figuring out how to stop treatment in patients who were taking Oxbryta. Pfizer hadn’t provided any guidance, so doctors were forced to experiment with their own tapering regimens.
“The reason you had this variation in recommendations, variation in care, is because we really didn’t know what the right answer [was],” said Strouse.
Physicians are still hunting for answers. Maureen Achebe, clinical director of hematology services at Brigham and Women’s Hospital and Dana-Farber Cancer Institute, explained during the session how the withdrawal has raised several questions about future sickle cell research. Among them: Are surrogate measures, like increases in hemoglobin, appropriate for regulatory clearance? Should approvals be limited to match the specific patient population involved in testing?
CAR-T’s next target in multiple myeloma
The past decade has brought a panoply of new drugs for multiple myeloma, a cancer of the blood and bone marrow. Among the most recent additions are treatments that target a protein found on malignant plasma cells and called GPRC5D for short. One, Johnson & Johnson’s bispecific antibody Talvey, has already been approved in the U.S.
Other companies are designing cell therapies that target the same protein. At ASH on Monday, Bristol Myers Squibb presented the first survival and cancer progression data for its candidate, a CAR-T treatment it’s now dubbed arlo-cel.
The results are from a Phase 1 study that enrolled people who had received at least three prior drugs for their multiple myeloma. Nearly 90% of the 79 study participants who were evaluable for drug efficacy responded to treatment, and just over a quarter experienced a complete response, or remission. The median time to cancer progression or death was 18 months, while median overall survival was not yet reached.
As with all CAR-T therapies, many treated patients experienced an immune reaction known as cytokine release syndrome, which was typically mild in severity. One patient with this side effect died, according to a study abstract. Three patients experienced hemophagocytic lymphohistiocytosis, another dangerous immune reaction, while eight had neurological toxicity.
Bristol Myers is testing arlo-cel further in a Phase 2 study called Quintessential. “We’re excited to disclose the progress of our robust pipeline, with promising early survival results for our GPRC5D-targeted cell therapy underscoring the first-in-class potential of [arlo-cel] for patients with relapsed or refractory multiple myeloma,” Bryan Campbell, a Bristol Myers Squibb cell therapy executive, said in a statement,
The company, which sells two cell therapies for myeloma and lymphoma, also presented data at ASH for a CD19-targeting CAR-T treatment in people with severe autoimmune diseases.
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- Source: https://www.biopharmadive.com/news/ash24-leukemia-drug-sequencing-sickle-cell-questions-and-a-new-kind-of-ca/735091/