AstraZeneca presented new data from across its hematology portfolio and pipeline at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, highlighting advancements in chronic lymphocytic leukemia (CLL), multiple myeloma (MM), paroxysmal nocturnal haemoglobinuria (PNH), and other hematologic diseases. The presentations included data on 13 approved and potential new medicines.
Calquence Shows Promise in CLL and MCL
Interim results from the AMPLIFY Phase III trial demonstrated the potential of fixed-duration Calquence (acalabrutinib) in combination with venetoclax, with or without obinutuzumab, in previously untreated adults with CLL compared to standard-of-care chemoimmunotherapy. The data were featured during the ASH Press Briefing on Sunday, December 8.
An updated analysis from the ECHO Phase III trial highlighted the use of Calquence in combination with bendamustine and rituximab as a first-line treatment option, demonstrating high and durable undetectable minimal residual disease (MRD) rates in previously untreated patients with mantle cell lymphoma (MCL). The benefit of Calquence was observed across all patients, including those with high-risk disease characteristics. These results were initially presented at the European Hematology Association (EHA) 2024 Hybrid Congress in June.
Results from the ChangE Phase III trial, evaluating Calquence compared with chlorambucil plus rituximab in first-line CLL patients in China, were also shared.
Advancing T-cell Engagers and CAR T Therapy
Two oral presentations shared results for the novel CD19xCD3 bispecific T-cell engager AZD0486, reinforcing its potential as a new treatment option for B-cell malignancies. Phase I results demonstrated a 96% overall response rate, an 85% complete response rate, and high rates of undetectable MRD in patients with relapsed/refractory follicular lymphoma (R/R FL) at doses of 2.4 mg and above. Interim Phase I results also showed early potential in patients with heavily pretreated diffuse large B-cell lymphoma (DLBCL). The safety profile of AZD0486 was reinforced, with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) events effectively mitigated by the double step-up dosing schedule.
Early data for AZD0120 (GC012F), a novel BCMAxCD19 dual-targeting autologous CAR T developed using the Gracell FasTCAR rapid manufacturing process, showed potential as a first-line therapy for elderly patients with newly diagnosed transplant ineligible MM. Preliminary results from the ongoing investigator-initiated trial of AZD0120 suggest deep responses and an acceptable safety profile, with no ICANS and no ≥Grade 2 CRS events observed in this patient population.
Preclinical data demonstrating the anti-tumour activity of AZD5492, a next-generation CD8 selective, CD20-targeting T-cell engager, designed using AstraZeneca’s innovative Target Induced T-cell Activating Nanobody (TITAN) platform, were also presented. AZD5492 is currently being evaluated in Phase I clinical trials in R/R Non-Hodgkin lymphoma (NHL) and CLL.
Voydeya Improves Outcomes in PNH
Data detailing events of breakthrough haemolysis (BTH) from the ALPHA trial evaluating Voydeya (danicopan) as add-on to Ultomiris (ravulizumab) or Soliris (eculizumab) in patients with PNH experiencing clinically significant extravascular haemolysis (EVH) and from the PEGASUS Phase III trial evaluating pegcetacoplan in patients with PNH previously treated with Soliris were presented. The data showed that 5/84 patients (6.0%) in the ALPHA trial and 19/80 patients (23.8%) in the PEGASUS trial experienced one or more BTH events. Most BTH events (6/7 or 85.7%) in the ALPHA trial were either mild or moderate, and all events were resolved without transfusion, dose modification, or treatment withdrawal.
Final long-term patient-reported outcomes from the ALPHA trial demonstrated that Voydeya as add-on to Ultomiris or Soliris resulted in sustained improvements in fatigue, quality of life, and physical function for up to 72 weeks in the subset of patients with PNH who experience clinically significant EVH.
Advancing Understanding of Rare Diseases
A US, retrospective chart review provided real-world evidence showing haematologic and renal improvements in adults with atypical haemolytic uraemic syndrome (aHUS) who switched to Ultomiris after short-term use of Soliris, with early responses and continued improvements through one year of treatment with Ultomiris.
Two presentations on amyloid light chain (AL) amyloidosis highlighted unmet medical needs in this progressive, debilitating disease, reinforcing the importance of bringing forward novel therapies to improve cardiovascular outcomes and organ function.
