AstraZeneca advances scientific leadership in haematology at ASH 2023

On November 28, 2023 AstraZeneca reported that it will present new clinical and real-world data in multiple haematological conditions at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in San Diego, CA, 9 to 12 December 2023 (Press release, AstraZeneca, NOV 28, 2023, View Source [SID1234638029]).

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A total of 63 abstracts will feature 14 approved and potential new medicines across the Company’s portfolio and pipeline including from Alexion, AstraZeneca’s Rare Disease group, in chronic lymphocytic leukaemia (CLL) and several types of lymphoma, paroxysmal nocturnal haemoglobinuria (PNH), atypical haemolytic uraemic syndrome (aHUS) and amyloid light-chain (AL) amyloidosis.

Anas Younes, Senior Vice President, Haematology R&D, AstraZeneca, said: "Our data at ASH (Free ASH Whitepaper) will exemplify how we are advancing a range of innovative modalities including antibody drug conjugates, next-generation immunotherapies and T-cell engagers in haematology. Updated clinical data for AZD0486, our CD19/CD3 T-cell engager, reinforce our belief in this approach as a potential new treatment for lymphoma, and new Calquence data continue to demonstrate long-term efficacy and safety in chronic lymphocytic leukaemia with further follow up."

Gianluca Pirozzi, Senior Vice President, Head of Development, Regulatory and Safety, Alexion, said: "Alexion has transformed the treatment landscape and redefined care for the paroxysmal nocturnal haemoglobinuria patient community over the past two decades. At the ASH (Free ASH Whitepaper) Annual Meeting, new results from our pivotal ALPHA trial will demonstrate the promise of Factor D inhibition to advance care for the small subset of patients with paroxysmal nocturnal haemoglobinuria who experience clinically significant extravascular haemolysis. We are proud to further our leadership in rare disease by sharing data from our robust haematology pipeline, reflecting our commitment to innovation and improving outcomes for the patients and families we serve."

Calquence continues to demonstrate long-term benefits in CLL

Six-year follow-up data from the pivotal ELEVATE-TN Phase III trial will further support the continued efficacy, safety and tolerability of Calquence for long-term use in patients with treatment-naïve CLL.1

Data from a Phase II trial will show the safety and efficacy of Calquence and rituximab followed by chemotherapy and autologous stem cell transplantation in fit patients with treatment-naïve mantle cell lymphoma (MCL).2

An analysis of five prospective Calquence trials, including three randomised, controlled Phase III trials and two non-randomised trials, will show acceptable safety outcomes based on rates of nonfatal and fatal ventricular arrhythmias and sudden death in patients with CLL.3

Novel early assets show potential to improve outcomes for blood cancer patients

Data from our early portfolio will demonstrate how the Company is advancing multiple modalities across several scientific platforms, including Immuno-Oncology, Immune-Engagers, Antibody Drug Conjugates (ADCs) and Epigenetics as part of its strategy to attack cancer from multiple angles.

Updated Phase I data for AstraZeneca’s CD19/CD3 T-cell engager, AZD0486, will further demonstrate the acceptable safety profile and high response rate of this treatment in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL).4 We will also present the first clinical data on sabestomig, a PD-1/TIM-3 targeting bispecific antibody, in R/R Hodgkin lymphoma, showing encouraging early signals of activity.5

The first preclinical data for AZD9829, a novel CD123-targeting ADC, using AstraZeneca’s proprietary linker technology to deliver a topoisomerase I inhibitor warhead, will demonstrate promising anti-tumour activity in acute myeloid leukaemia.6 In addition, preclinical data will demonstrate anti-tumour activity of AstraZeneca’s novel PRMT5 inhibitor in MTAP silenced Hodgkin lymphoma models.7

Showcasing advances to bolster our leadership in PNH with new data on Factor D inhibition and impact of C5 inhibition in long-term disease control

New results from the 24-week and long-term extension period from the pivotal ALPHA Phase III trial will reinforce the potential for danicopan add-on therapy to address clinically significant extravascular haemolysis (EVH) in the small subset of PNH patients who experience this condition while treated with C5 inhibitor therapy, allowing them to maintain control of intravascular haemolysis (IVH) through standard-of-care treatment with Ultomiris (ravulizumab) or Soliris (eculizumab).8

Further, patient-reported outcomes from the ALPHA trial will suggest danicopan as an add-on to Ultomiris or Soliris improved quality of life compared to C5 inhibitor therapy alone in patients with PNH who experience clinically significant EVH.9

Additionally, Alexion will present an analysis of six-year outcomes from the Phase III clinical trial evaluating the safety and efficacy of Ultomiris in patients with PNH who did not have previous treatment with a C5 inhibitor.10 The analysis compared survival against untreated patients in the International PNH Registry, the largest global real-world database of patients with PNH. Results will suggest Ultomiris improved survival and maintained effective long-term control of IVH, the most significant contributor to morbidity and premature mortality in PNH.10

Improving diagnosis and management of life-threatening rare diseases, including amyloidosis

24-month results of a Phase II trial will demonstrate the safety and tolerability of CAEL-101 in combination with cyclophosphamide-bortezomib-dexamethasone with or without daratumumab for the treatment of AL amyloidosis.11

Real-world analyses across AL amyloidosis, aHUS and haematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) will also be presented, advancing the scientific understanding of these rare, haematological conditions.12-16

Key presentations during the 65th ASH (Free ASH Whitepaper) Annual Meeting and Exposition

Lead author

Abstract title

Presentation details

Calquence (acalabrutinib)
Sharman, JP

Acalabrutinib ± Obinutuzumab vs Obinutuzumab + Chlorambucil in Treatment-naive Chronic Lymphocytic Leukemia: 6-year Follow-up of ELEVATE-TN

Abstract # 636

Oral Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Frontline Treatment with Targeted Agents in Patients with Chronic Lymphocytic Leukemia

10 December 2023

17:45 PST

Location: Seaport Ballroom ABCD (Manchester Grand Hyatt San Diego)

Westin, J

Smart Stop: Lenalidomide, Tafasitamab, Rituximab and Acalabrutinib Alone and with Combination Chemotherapy for the Treatment of Newly Diagnosed Diffuse Large B-cell Lymphoma

Abstract # 856

Oral Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Initial treatment strategies in Aggressive B-Cell Lymphomas

11 December 2023

15:30 PST

Location: Seaport Ballroom ABCD (Manchester Grand Hyatt San Diego)

Hawkes, EA

A Window Study of Acalabrutinib and Rituximab, Followed by Chemotherapy and Autograft (ASCT) in Fit Patients with Treatment-naïve Mantle Cell Lymphoma (MCL): First Report of the Investigator-initiated Australasian Leukaemia and Lymphoma Group NHL33 ‘WAMM’ Trial

Abstract # 735

Oral Session: 623. Mantle Cell, Follicular and Other Indolent B-Cell Lymphomas: Clinical and Epidemiological: Prospective Clinical Trials in Mantle Cell Lymphoma Incorporating Novel Agents

11 December 2023

11:00 PST

Location: Grand Hall B (Manchester Grand Hyatt San Diego)

Hawkes, EA

TrAVeRse: A Phase 2, Open-Label, Randomized Study of Acalabrutinib in Combination with Venetoclax and Rituximab in Patients with Treatment- naïve Mantle Cell Lymphoma

Abstract # 3054

Poster Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphomas: Clinical and Epidemiological: Poster II

10 December 2023

18:00 – 20:00 PST

Location: Halls G-H (San Diego Convention Center)

Sharman, J

Analysis of Ventricular Arrhythmias and Sudden Death with Acalabrutinib From 5 Prospective Clinical Trials

Abstract # 4643

Poster Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster III

11 December 2023

18:00 – 20:00 PST

Location: Halls G-H (San Diego Convention Center)

Ferrajoli, A

Cumulative Review of Hypertension in Patients with Chronic Lymphocytic Leukemia (CLL) and Other Hematologic Malignancies Treated with Acalabrutinib: Data from Clinical Trials

Abstract # 1917

Poster Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster I

9 December 2023

17:30 – 19:30 PST

Location: Halls G-H (San Diego Convention Center)

Sun, C

Extended Follow-Up and Resistance Mutations in CLL Patients Treated with Acalabrutinib

Abstract # 1891

Poster Session: 641. Chronic Lymphocytic Leukemias: Basic and Translational: Poster I

9 December 2023

17:30 – 19:30 PST

Location: Halls G-H (San Diego Convention Center)

Jain, P

Acalabrutinib with Rituximab as First-line Therapy for Older Patients with Mantle Cell Lymphoma – A Phase II Clinical Trial

Abstract # 3036

Poster Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphomas: Clinical and Epidemiological: Poster II

10 December 2023

18:00 – 20:00 PST

Location: Halls G-H (San Diego Convention Center)

Perini, G

ACRUE: A Phase 2, Open-label Study of Acalabrutinib in Combination with Rituximab in Elderly and/or Frail Patients with Treatment-naïve Diffuse Large B-Cell Lymphoma

e-Publication

Online Only

AZD0486
Gaballa, S

Double Step-Up Dosing (2SUD) Regimen Mitigates Severe ICANS and CRS While Maintaining a High Efficacy in Subjects with Relapsed/Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) Treated with AZD0486, a Novel CD19xCD3 T-cell Engager (TCE): Updated Safety and Efficacy Data from the Ongoing First-in-Human (FIH) Phase I Trial

Abstract # 1662

Poster Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphomas: Clinical and Epidemiological: Poster I

9 December 2023

17:30 – 19:30 PST

Location: Halls G-H (San Diego Convention Center)

AZD9829

Dutta, D

First Disclosure of AZD9829, a TOP1i-ADC Targeting CD123: Promising Preclinical Activity in AML Models with Minimal Effect on Healthy Progenitors

e-Publication

Online Only

AZD7789

Mei, M

Safety and Preliminary Efficacy of Sabestomig (AZD7789), an Anti-PD-1 and Anti-TIM-3 Bispecific Antibody, in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma Previously Treated with Anti-PD-(L)1 Therapy

Abstract # 4433

Poster Session: 624. Hodgkin Lymphomas and T/NK cell Lymphomas: Clinical and Epidemiological: Poster III

11 December 2023

18:00 – 20:00 PST

Location: Halls G-H (San Diego Convention Center)

PRMT5 inhibitor

Urosevic, J

Epigenetic Silencing of MTAP in Hodgkin’s Lymphoma Renders it Sensitive to a 2nd Generation PRMT5 Inhibitor

Abstract # 4185

Poster Session: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster III

11 December 2023

18:00 – 20:00 PST

Location: Halls G-H (San Diego Convention Center)

Danicopan

Kulasekararaj, A

Danicopan as Add-On Therapy to Ravulizumab or Eculizumab Versus Placebo in Patients with Paroxysmal Nocturnal Hemoglobinuria and Clinically Significant Extravascular Hemolysis: Phase 3 Long-term Data

Abstract # 576

Oral Session: 508. Bone Marrow Failure: Acquired: Unraveling the Future of PNH Therapy from Clinical Trials

10 December 2023

17:45 PST

Location: Room 7 (San Diego Convention Center)

Piatek, C

Patient-reported Outcomes: Danicopan as Add-On Therapy to Ravulizumab or Eculizumab Versus Placebo in Patients with Paroxysmal Nocturnal Hemoglobinuria and Clinically Significant Extravascular Hemolysis

Abstract # 1346

Poster Session: 508. Bone Marrow Failure: Acquired: Poster I

9 December 2023

17:30 – 19:30 PST

Location: Halls G-H (San Diego Convention Center)

Ultomiris (ravulizumab)

Kulasekararaj, A

Ravulizumab Provides Durable Control of Intravascular Hemolysis and Improves Survival in Patients with Paroxysmal Nocturnal Hemoglobinuria: Long-Term Follow-Up of Study 301 and Comparisons with Patients of the International PNH Registry

Abstract # 2714

Poster Session: 508. Bone Marrow Failure: Acquired: Poster II

10 December 2023

18:00 – 20:00 PST

Location: Halls G-H (San Diego Convention Center)

Röth, A

Ravulizumab Effectiveness in the Real-world: Evidence from the International PNH Registry

Abstract # 2722

Poster Session: 508. Bone Marrow Failure: Acquired: Poster II

10 December 2023

18:00 – 20:00 PST

Location: Halls G-H (San Diego Convention Center)

Piatek, C

Efficacy and Safety of Subcutaneous Ravulizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria Who Received Prior Intravenous Eculizumab: 2-Year Follow-Up

Abstract # 2713

Poster Session: 508. Bone Marrow Failure: Acquired: Poster II

10 December 2023

18:00 – 20:00 PST

Location: Halls G-H (San Diego Convention Center)

CAEL-101

Valent, J

Safety and Tolerability of CAEL-101, an Anti-Amyloid Monoclonal Antibody, Combined with Anti-Plasma Cell Dyscrasia Therapy in Patients with Light-Chain Amyloidosis: 24-Month Results of a Phase 2 Study

Abstract # 540

Oral Session: 654. MGUS, Amyloidosis and Other Non-Myeloma Plasma Cell Dyscrasias: Clinical and Epidemiological: From Light Chain to Fibril–Novel Diagnostics to Treatments for Amyloidosis

10 December 2023

13:15 PST

Location: Seaport Ballroom EFGH (Manchester Grand Hyatt San Diego)

Costello, M

CAEL-101 Enhances the Clearance of Light Chain Fibrils and Intermediate Aggregates by Phagocytosis

Abstract # 3307

Poster Session: 651. Multiple Myeloma and Plasma Cell Dyscrasias: Basic and Translational: Poster II

10 December 2023

18:00 – 20:00 PST

Location: Halls G-H (San Diego Convention Center)

AL Amyloidosis

Lyons, G

Treatment Patterns and Outcomes for Patients with Light Chain (AL) Amyloidosis: Analysis of a Large US Claims Database

e-Publication

Online Only

Thompson, J

Real-world Treatment Patterns Following Update to National Comprehensive Cancer Network Guidelines for Light-Chain Amyloidosis: Results from a US Administrative Claims Database

e-Publication

Online Only

Laires, P

Prevalence, Incidence, and Characterization of Light Chain Amyloidosis in the USA: A Real-world Analysis Utilizing Electronic Health Records (EHR)

e-Publication

Online Only

aHUS

Wang, Y

Patient Characteristics and Diagnostic Journey of Thrombotic Microangiopathy Associated with a Trigger: A Real-world, Retrospective, Multi-national Study

e-Publication

Online Only

HSCT-TMA

Wang, Y

Real-world Analysis of the Underdiagnosis, Clinical Outcomes and Associated Burden of Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy (HSCT-TMA) in the United States of America

Abstract # 491

Oral Session: 904. Outcomes Research – Non-Malignant Conditions: What to Know: Management Costs and Outcomes in Various Non-Malignant Disorders

10 December 2023

10:30 PST

Location: Pacific Ballroom Salons 15-17 (Marriott Marquis San Diego Marina)

PNH

Wagner-Ballon, O

Neutrophil PNH Type II Cells Are Associated with Thrombosis and Bone Marrow Failure Without Hemolysis: Evidence from Analysis of the 5-year French Nation-Wide Multicenter Observational Study

Abstract # 4083

Poster Session: 508. Bone Marrow Failure: Acquired: Poster III

11 December 2023

18:00 – 20:00 PST

Location: Halls G-H (San Diego Convention Center)