ASH 2024: Advances in Leukemia, Sickle Cell Disease, and Multiple Myeloma Therapies
Key Insights
Lilly's Jaypirca demonstrated superior efficacy in relapsed/refractory CLL patients previously treated with BTK inhibitors, nearly doubling the time to disease progression compared to older regimens.
AstraZeneca's Calquence, combined with Venclexta, reduced the risk of disease progression or death by 35% in previously untreated CLL, offering a potential alternative to chemoimmunotherapy.
Pfizer's withdrawal of Oxbryta for sickle cell disease (search) raised concerns about safety monitoring and data transparency, prompting discussions on appropriate endpoints for regulatory approvals.
The American Society of Hematology (ASH) 2024 annual meeting featured key updates in blood disease research, including advancements in chronic lymphocytic leukemia (search) (CLL), sickle cell disease (search), and multiple myeloma (search).
BTK Inhibitor Sequencing in CLL
With the increasing use of BTK inhibitors like Imbruvica in CLL treatment, researchers are exploring optimal sequencing strategies. Lilly's study of Jaypirca, a BTK inhibitor with a slightly different mechanism, is the first randomized Phase 3 trial exclusively enrolling CLL patients previously treated with another BTK inhibitor. Results indicated that Jaypirca nearly doubled the time to disease progression or death compared to investigator's choice of older drug regimens and substantially lengthened the median time to next treatment or death by 13 months over the control group. Additionally, treatment with Jaypirca led to fewer severe side effects. These data are intended to serve as confirmatory evidence for the accelerated approval of Jaypirca in the U.S. for adults with CLL who have received at least two prior lines of therapy.
AstraZeneca presented results from a study combining Calquence with Venclexta in previously untreated CLL patients. The combination reduced the risk of disease progression or death by 35% versus standard chemoimmunotherapy. Adding Gazyva further lowered the risk but increased side effects. According to Jacob Van Naarden, head of Lilly Oncology, these results raise the question of whether physicians might want to try Jaypirca instead of Venclexta after a patient’s disease progresses on their first BTK inhibitor.
Concerns Arise Over Sickle Cell Drug Recall
The abrupt withdrawal of Pfizer's Oxbryta from the market due to safety concerns, including an imbalance in deaths and higher rates of sickle cell pain crises, surprised many in the field. John Strouse, a hematologist and sickle cell specialist at Duke University, noted the surprise and concern among physicians. The lack of guidance from Pfizer on how to discontinue Oxbryta treatment led to varied approaches by physicians. Maureen Achebe from Brigham and Women's Hospital and Dana-Farber Cancer Institute highlighted the questions raised about surrogate measures for regulatory clearance and the need to match approvals to specific patient populations involved in testing.
CAR-T Therapy Advances in Multiple Myeloma
Bristol Myers Squibb (search) presented Phase 1 data for arlo-cel (search), a CAR-T therapy targeting GPRC5D (search) in multiple myeloma (search) patients who had received at least three prior therapies. Nearly 90% of evaluable patients responded to treatment, with just over a quarter experiencing a complete response or remission. The median time to cancer progression or death was 18 months, and the median overall survival was not yet reached. While cytokine release syndrome and neurological toxicity were observed, the results suggest the potential of arlo-cel as a novel treatment option. Bristol Myers Squibb is further evaluating arlo-cel in the Phase 2 Quintessential study.