Nicholas Williams, Joe Lee, Luiza Moore, et al. and Jyoti Nangalia
Conclusions: MPN originate from driver mutation acquisition very early in life, even before birth, with life-long clonal expansion and evolution, establishing a new paradigm for blood cancer development. Early detection of mutant-JAK2 together with the determination of clonal expansion rates could provide opportunities for early interventions aimed at minimizing thrombotic risk and targeting the mutant clone in at-risk individuals.
Asciminib Found Safe and Effective for Hard-to-Treat Chronic Myeloid Leukemia (LBA-4)
“Asciminib may provide a good opportunity for a third-line treatment in CML patients,” said senior study author Dr. Andreas Hochhaus, of the University Hospital, Jena, Germany. “The ASCEMBL data show that, with ABL-specific inhibition, asciminib has a reduced rate of side effects that lead to discontinuation or dose adjustment compared to the TKI drug bosutinib, while improving the response rate and speed of response.”
LBA-4 Efficacy and Safety Results from ASCEMBL, a Multicenter, Open-Label, Phase 3 Study of Asciminib, a First-in-Class STAMP Inhibitor, vs Bosutinib (BOS) in Patients (Pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Previously Treated with ≥2 Tyrosine Kinase Inhibitors (TKIs)
Andreas Hochhaus, Carla Boquimpani, Delphine Rea, et al.
Conclusions: In this first controlled study comparing treatments for resistant/intolerant (R/I) pts with CML, asciminib, a first-in-class STAMP inhibitor, demonstrated statistically significant and clinically meaningful superiority in efficacy compared with BOS (primary objective), deeper MR rates, and a favorable safety profile. These results support the use of asciminib as a new treatment option in CML, particularly in R/I pts who received ≥2 prior TKIs.
Gene Therapy for Hemophilia B Found Safe and Effective in First Phase III Trial (LBA-6)
“Most patients with hemophilia B are bound to a prophylactic factor regimen of one to two intravenous infusions per week from birth through the rest of their life,” said senior study author Steven W. Pipe, MD, of the University of Michigan, Ann Arbor. “Gene therapy offers the chance to liberate patients from the burden of their prior treatments, allowing for spontaneity and the freedom to do more in day-to-day life.”
LBA-6 First Data from the Phase 3 HOPE-B Gene Therapy Trial: Efficacy and Safety of Etranacogene Dezaparvovec (AAV5-Padua hFIX variant; AMT-061) in Adults with Severe or Moderate-Severe Hemophilia B Treated Irrespective of Pre-Existing Anti-Capsid Neutralizing Antibodies
Steven W. Pipe, Michael Recht, Nigel S. Key, et al.
Conclusions: The first co-primary endpoint of this study was met. This is the first report of a Phase 3 study in HB and the largest gene therapy trial cohort to date. Following a single dose of etranacogene dezaparvovec, FIX activity increased, without the need for prophylactic immunosuppression, into the mild-to-normal range at 26wks in pts with severe/moderately severe HB. Importantly, this included pts with titers of pre-existing anti-AAV5 NAbs. Pts were able to discontinue prophylaxis and bleeding was abolished in the majority. The safety profile was consistent with early phase AAV5 studies and together these data support a favorable safety and efficacy profile for etranacogene dezaparvovec