AstraZeneca advances its ambition to redefine cancer care with new data across its industry-leading and diverse pipeline in haematology at the 66[th] American Society of Hematology (ASH) Annual Meeting and Exposition 7 to 10 December 2024.

A total of 57 abstracts will feature 13 approved and potential new medicines from across AstraZeneca's portfolio and pipeline in haematology, including from Alexion, its rare disease group, with data in key settings including chronic lymphocytic leukaemia (CLL), multiple myeloma (MM), paroxysmal nocturnal haemoglobinuria (PNH) and other haematologic diseases.

Anas Younes, Senior Vice President, Haematology R&D, AstraZeneca, said: "Our data at ASH from the AMPLIFY Phase III trial will demonstrate the efficacy and safety of our leading second-generation BTK inhibitor, Calquence, as a fixed-duration therapy in first-line CLL. In addition, new results for our novel T-cell engager, AZD0486, will reinforce its promising clinical profile in lymphomas, and data for our novel CAR T cell therapy, AZD0120, will highlight the potential of this therapy to transform treatment in multiple myeloma."

Christophe Hotermans, Senior Vice President, Head of Global Medical Affairs, Alexion, said: "Our ASH presentations will highlight the transformative impact of our medicines, including new analyses from the ALPHA Phase III trial reaffirming the safety and efficacy of our first-in-class Factor D inhibitor Voydeya as add-on to Ultomiris or Soliris for the subset of patients with PNH experiencing clinically significant extravascular haemolysis. Further, new insights from our robust pipeline will enhance the understanding of several rare haematologic and cardiovascular conditions, underscoring our commitment to innovation in rare disease."

Calquence combinations demonstrate significant benefits across CLL and MCL

An oral presentation on interim results from the pivotal AMPLIFY Phase III trial will demonstrate the potential of fixed-duration Calquence in combination with venetoclax, with or without obinutuzumab, in previously untreated adults with CLL compared to standard-of-care chemoimmunotherapy.[1] These results will be featured during the ASH Press Briefing on Sunday 8 December.

An updated analysis from the pivotal ECHO Phase III trial will further highlight the use of Calquence in combination with bendamustine and rituximab as a first-line treatment option by demonstrating high and durable undetectable minimal residual disease (MRD) rates in previously untreated patients with mantle cell lymphoma (MCL) as well as showing the benefit of Calquence across all patients including those with high-risk disease characteristics.[2] Results from ECHO were first presented (https://www.astrazeneca.com/media-centre/press-releases/2024/calquence-plus-chemoimmunotherapy-reduced-the-risk-of-disease-progression-or-death-by-27-percent.html) as a late-breaking oral presentation at the European Hematology Association (EHA) 2024 Hybrid Congress in June.[3]

Results will also be shared from the ChangE Phase III trial, evaluating Calquence compared with chlorambucil plus rituximab in first-line CLL in patients in China.[4]

New data show promise of next generation T-cell engagers and chimeric antigen receptor T-cell (CAR T) therapy

Two oral presentations will share results for the novel CD19xCD3 bispecific T-cell engager AZD0486, reinforcing the potential of this novel medicine as a new treatment option for B-cell malignancies.[5,6] Phase I results demonstrate high response rates, with a 96% overall response rate, 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.[5] Additionally, interim Phase I results will show the early potential of AZD0486 in patients with heavily pretreated diffuse large B-cell lymphoma (DLBCL).[6] Data will also reinforce the safety profile of AZD0486, with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) events effectively mitigated by the double step-up dosing schedule.[7]   

Early data for AZD0120 (GC012F), a novel BCMAxCD19 dual-targeting autologous CAR T developed using the Gracell FasTCAR  rapid manufacturing process, will show potential as a first-line therapy for elderly patients with newly diagnosed transplant ineligible MM.[8] 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.[8]

An oral presentation will share 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. AZD5492 is currently being evaluated in Phase I clinical trials in R/R Non-Hodgkin lymphoma (NHL) and CLL.[9 ]

Voydeya (danicopan) as add-on to Ultomiris (ravulizumab) or Soliris (eculizumab) demonstrates low rate of mild or moderate BTH events and improves quality of life measures in patients with PNH and clinically significant EVH

Data will be presented detailing events of breakthrough haemolysis (BTH), a key indicator of intravascular haemolysis and PNH disease control, reported in the ALPHA trial evaluating Voydeya as add-on to Ultomiris or Soliris in patients with PNH experiencing clinically significant extravascular haemolysis (EVH) and separately in the PEGASUS Phase III trial evaluating pegcetacoplan in patients with PNH previously treated with Soliris. Data will show 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. Moreover, 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.[10]

Separately, final long-term patient-reported outcomes from the ALPHA trial will demonstrate 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.[11] 

Advancing understanding of life-threatening rare diseases 

A US, retrospective chart review will provide 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.[12]

Additionally, two presentations on amyloid light chain (AL) amyloidosis will highlight unmet medical needs in this progressive, debilitating disease, reinforcing the importance of bringing forward novel therapies to improve cardiovascular outcomes and organ function.[13,14]

Key presentations during the 66th ASH Annual Meeting and Exposition

[]
Lead Author Abstract Title Presentation details (PST)
Calquence
(acalabrutinib)
Brown, JR et al. Fixed-Duration Abstract #1009Oral Session 642: Chronic
Acalabrutinib plus Lymphocytic Leukemia: Clinical and
Venetoclax with or Epidemiological: Frontline Targeted
without Therapy Combinations 9 December 2024
Obinutuzumab 4:30 PM
versus
Chemoimmunotherapy
for First-Line
Treatment of
Chronic
Lymphocytic
Leukemia: Interim
Analysis of the
Multicenter, Open
-label,
Randomized, Phase
3 AMPLIFY Trial
Qiu, L et al. Acalabrutinib Abstract #3251Poster Session 642:
Versus Chronic Lymphocytic Leukemia: Clinical
Chlorambucil Plus and Epidemiological: Poster II8 December
Rituximab in 2024 6:00 - 8:00 PM 
Patients with
Previously
Untreated Chronic
Lymphocytic
Leukemia: A
Randomized,
Multicenter, Open
Label, Phase 3
Study
Dreyling, M et High-risk Abstract #1626Poster Session 623. Mantle
al. Subgroups and MRD: Cell, Follicular, Waldenstrom's and
An Updated Other Indolent B Cell Lymphomas:
Analysis of the Clinical and Epidemiological: Poster I7
Phase 3 ECHO Trial December 2024 5:30 - 7:30 PM 
of Acalabrutinib
with
Bendamustine/Rituxi
mab in Previously
Untreated Mantle
Cell Lymphoma
Simon, F et al. Efficacy and Abstract #4618 Poster Session 642:
Safety of Chronic Lymphocytic Leukemia: Clinical
Acalabrutinib and Epidemiological: Poster III 9
Treatment in Very December 2024 6:00 - 8:00 PM 
Old (≥80y) and/or
Frail Patients
with Chronic
Lymphocytic
Leukemia (CLL) -
Primary Endpoint
Analysis of the
Phase II CLL-Frail
Trial
Swaminathan, M Early Obinutuzumab Abstract #1855Poster Session 642:
et al. Significantly Chronic Lymphocytic Leukemia: Clinical
Increases Bone and Epidemiological: Poster I7 December
Marrow 2024 5:30 - 7:30 PM 
Undetectable MRD
(10[-4
]sensitivity)
(uMRD4) Rate when
Combined with
Acalabrutinib and
Venetoclax in a
Randomized Phase
II Trial for
Treatment Naïve
CLL
Jerkeman, M et Acalabrutinib and Abstract #747 Oral Session 623: Mantle
al. Rituximab in Cell, Follicular, Waldenstrom's and
Elderly Patients Other Indolent B Cell Lymphomas:
with Newly Clinical and Epidemiological: Updates on
Diagnosed Mantle Drug Treatments for Mantle Cell
Cell Lymphoma Lymphoma, and CAR-T and Transplants for
Including a Indolent Lymphomas9 December 2024 11:00
Matched Population AM 
-Based External
Comparator- the
Nordic Lymphoma
Group NLG-MCL8
(ALTAMIRA) Phase
II Trial
Christofyllakis, Toxicity of R-mini Abstract #4498 Poster Session 627:
K et al. -CHOP with or Aggressive Lymphomas: Pharmacologic
without Therapies: Poster III9 December
Acalabrutinib in 2024 6:00 - 8:00 PM 
Older Adults with
Untreated DLBCL -
An Interim
Analysis of
Serious Adverse
Events in the
ARCHED / GLA 2022
-1 Randomized,
Open-Label, Phase
3 Trial
AZD0486
Gaballa, S et Evaluation of Abstract #868 Oral Session 627:
al. AZD0486, a Novel Aggressive Lymphomas: Pharmacologic
CD19xCD3 T-Cell Therapies: Novel Monotherapies or Novel
Engager, in Disease Indications9 December 2024 3:30
Relapsed/Refractory PM 
Diffuse Large B
-cell Lymphoma in
an Ongoing First
-in-Human Phase 1
Study: High
Complete Responses
Seen in CAR
-T-naive and CAR
-T-exposed
Patients
Hou, J et al. Escalating Doses Abstract #341Oral Session 623: Mantle
of AZD0486, a Cell, Follicular, Waldenstrom's and
Novel CD19xCD3 T Other Indolent B Cell Lymphomas:
-cell Engager, Clinical and Epidemiological: Novel
Result in High Treatment Strategies and New Data on Old
Complete Standards for Follicular Lymphoma 7
Remissions with December 2024 5:00 PM 
Rapid Clearance of
Minimal Residual
Disease in
Patients with
Relapsed/Refractory
Follicular
Lymphoma
Zhu, X et al. Exposure-Response Abstract #2794Poster Session 605:
analysis and Molecular Pharmacology and Drug
Quantitative Resistance: Lymphoid Neoplasms: Poster
Systems II8 December 2024 6:00 - 8:00 PM 
Pharmacology
modelling for an
optimal dose
selection of
AZD0486 in
follicular
lymphoma patients
AZD0120
Du, J et al.  A phase I study Abstract #2072Poster Session 704:
of dual targeting Cellular Immunotherapies: Early Phase
BCMA and CD19 Clinical Trials and Toxicities: Poster
FasTCAR-T cells I7 December 2024 5:30 - 7:30 PM
(GC012F) as first
-line therapy for
transplant
-ineligible newly
diagnosed multiple
myeloma
AZD5492
Lawrence, R et Pre-Clinical Abstract #959Oral Session 605: Molecular
al. Evaluation of Pharmacology and Drug Resistance:
AZD5492, a Novel Lymphoid Neoplasms: Novel Therapeutic
CD8-Guided T Cell Approaches in Lymphoma9 December
Engager, for B-Non 20245:30 PM
-Hodgkin Lymphoma
Indications
Voydeya
(danicopan)
Schrezenmeier, H Breakthrough Abstract #2694Poster Session 508: Bone
Hemolysis Events Marrow Failure: Acquired: Poster II8
in Patients with December 20246:00 PM
Paroxysmal
Nocturnal
Hemoglobinuria:
Data from
Danicopan and
Pegcetacoplan
Trials
Piatek, C Danicopan as Add Abstract #2692Poster Session 508: Bone
-On Therapy to Marrow Failure: Acquired: Poster II8
Ravulizumab or December 20246:00 PM
Eculizumab in
Patients with
Paroxysmal
Nocturnal
Hemoglobinuria:
Long-Term Patient
-Reported Outcomes
from the Phase 3
ALPHA Trial
Ultomiris
(ravulizumab)
and Soliris
(eculizumab)
Griffiths, E Real-World Drug Abstract #5074Poster Session 905:
Adherence, Outcomes Research: Non-Malignant
Persistence, and Conditions Excluding Hemoglobinopathies
Healthcare 9 December 20246:00 PM
Resource
Utilization in
Patients with
Paroxysmal
Nocturnal
Hemoglobinuria in
the USA: The
ADVANTAGE Study
Chaturvedi, S Real-World Abstract #2613Poster Session 330:
Effectiveness of Vascular Biology, Thrombosis, and
Ravulizumab Among Thrombotic Microangiopathies: Basic and
Adults with Translational 8 December 20246:00 PM
Atypical Hemolytic
Uremic Syndrome
(aHUS) who
Switched to
Ravulizumab Within
3 Months of
Eculizumab
Treatment: A
Physician Panel
-Based Chart
Review Study (aHUS
IMPACT)
Iori, AP REACTION - Real Abstract #2464Poster Session 101: Red
Life Use of Cells and Erythropoiesis, Excluding
Ravulizumab in Iron8 December 20246:00 PM
Italian PatiEnts
with PAroxysmal
NoCturnal
Hemoglobinuria a
MulTicenter
ObservatIONal
Retrospective and
Prospective Cohort
Study, Final
Results
PNH
Wagner-Ballon, O High Proportion of Abstract #4080Poster Session 508: Bone
PNH Type II Marrow Failure: Acquired: Poster III9
Neutrophils, l.e December 20246:00 PM
Relative
Percentage 3%, Is
Associated with
Thrombosis in
Patients
Displaying a PNH
Clone >1%:
Evidence from
Analysis of the 5
-Year French
Nation-Wide
Multicenter
Observational
Study
HSCT-TMA
Dandoy, C Survival Outcomes Abstract #7286Online Publication
in Adult and
Pediatric Patients
Who Experienced
Thrombotic
Microangiopathy
After
Hematopoietic Stem
Cell Transplant: A
Systematic Review
and Meta-Analysis
Amyloidosis
Laires, P Comparison Of Abstract #6887Online Publication
Alternative Mayo
Staging
Classification
Systems Used in
Light-Chain
Amyloidosis
Thompson, J Evaluation of Abstract #4677Poster Session 652: MGUS,
Functional Cardiac Amyloidosis, and Other Non-Myeloma
Measures and Plasma Cell Dyscrasias: Clinical and
Response to Epidemiological9 December 20246:00 PM
Treatment
Initiation in
Patients with
Systemic Light
-Chain (AL)
Amyloidosis:
Results from a
Single Site
Retrospective
Study

Notes

AstraZeneca in haematology

AstraZeneca is pushing the boundaries of science to redefine care in haematology. Our goal is to help transform the lives of patients living with malignant, rare and other related haematologic diseases through innovative medicines and approaches that are shaped by insights from patients, caregivers and physicians.

In addition to our marketed products, we are spearheading the development of novel therapies designed to target underlying drivers of disease across multiple scientific platforms. Our acquisitions of Alexion, with expertise in rare, non-malignant blood disorders, and Gracell Biotechnologies Inc., pioneers of autologous cell therapies, expand our haematology pipeline and enable us to reach more patients with high unmet needs through the end-to-end discovery, development and delivery of novel therapies.

AstraZeneca in oncology

AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

Alexion
Alexion, AstraZeneca Rare Disease is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and delivery of life-changing medicines. A pioneering leader in rare disease for more than three decades, Alexion was the first to translate the complex biology of the complement system into transformative medicines, and today it continues to build a diversified pipeline across disease areas with significant unmet need, using an array of innovative modalities. As part of AstraZeneca, Alexion is continually expanding its global geographic footprint to serve more rare disease patients around the world. It is headquartered in Boston, US.    

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com (http://www.astrazeneca.com/) and follow the Company on Social Media @AstraZeneca (https://www.linkedin.com/company/astrazeneca).

Contacts
For details on how to contact the Investor Relations Team, please click here (https://www.astrazeneca.com/investor-relations.html#Contacts). For Media contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html).

References

1. Brown, J et al. Fixed-Duration Acalabrutinib plus Venetoclax with or without Obinutuzumab versus Chemoimmunotherapy for First-Line Treatment of Chronic Lymphocytic Leukemia: Interim Analysis of the Multicenter, Open-label, Randomized, Phase 3 AMPLIFY Trial. Presented at ASH 2024. Abstract 1009. 2024.
2. Dreyling, M et al. High-risk Subgroups and MRD: An Updated Analysis of the Phase 3 ECHO Trial of Acalabrutinib with Bendamustine/Rituximab in Previously Untreated Mantle Cell Lymphoma. Presented at ASH 2024. Abstract 1626. 2024.
3. Wang, M et al. Acalabrutinib plus bendamustine and rituximab in untreated mantle cell lymphoma: Results from the Phase 3, Double-Blind, Placebo-Controlled ECHO Trial. Presented at EHA 2024. Abstract LBA3439. 2024
4. Qiu, L et al. Acalabrutinib Versus Chlorambucil Plus Rituximab in Patients with Previously Untreated Chronic Lymphocytic Leukemia: A Randomized, Multicenter, Open Label, Phase 3 Study. Presented at ASH 2024. Abstract 3251. 2024.
5. Gaballa, S et al. Evaluation of AZD0486, a Novel CD19xCD3 T-Cell Engager, in Relapsed/Refractory Diffuse Large B-cell Lymphoma in an Ongoing First-in-Human Phase 1 Study: High Complete Responses Seen in CAR-T-naive and CAR-T-exposed Patients. Presented at ASH 2024. Abstract 868. 2024.
6. Hou, J et al. Escalating Doses of AZD0486, a Novel CD19xCD3 T-cell Engager, Result in High Complete Remissions with Rapid Clearance of Minimal Residual Disease in Patients with Relapsed/Refractory Follicular Lymphoma. Presented at ASH 2024. Abstract 341. 2024.
7. Zhu, X et al. Exposure-Response analysis and Quantitative Systems Pharmacology modelling for an optimal dose selection of AZD0486 in follicular lymphoma patients. Presented at ASH 2024. Abstract 2794. 2024.
8. Du, J et al. A phase I study of dual targeting BCMA and CD19 FasTCAR-T cells (GC012F) as first-line therapy for transplant-ineligible newly diagnosed multiple myeloma. Presented at ASH 2024. Abstract 2072. 2024.
9. Lawrence, R et al. Pre-Clinical Evaluation of AZD5492, a Novel CD8-Guided T Cell Engager, for B-Non-Hodgkin Lymphoma Indications. Presented at ASH 2024. Abstract 959. 2024.
10. Schrezenmeier H, Mahdi M, Gasteyger C, et al. Breakthrough Hemolysis Events in Patients with Paroxysmal Nocturnal Hemoglobinuria: Data from Danicopan and Pegcetacoplan Trials. Presented at ASH 2024. Abstract 2694. 2024.
11. Piatek C, Lee JW, Griffin M, et al. Danicopan as Add-On Therapy to Ravulizumab or Eculizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria: Long-Term Patient-Reported Outcomes from the Phase 3 ALPHA Trial. Presented at ASH 2024. Abstract 2692. 2024.
12. Chaturvedi S, Wang Y, Ong M-L, et al. Real-World Effectiveness of Ravulizumab Among Adults with Atypical Hemolytic Uremic Syndrome (aHUS) who Switched to Ravulizumab Within 3 Months of Eculizumab Treatment: A Physician Panel-Based Chart Review Study (aHUS IMPACT). Presented at ASH 2024. Abstract 2613. 2024.
13. Laires P, Thompson J, Catini J, et al. Comparison of Alternative Mayo Staging Classification Systems Used in Light-Chain Amyloidosis. Presented at ASH 2024. Abstract 6887. 2024.
14. Thompson J, Catini J, Ouyang D, et al. Evaluation of Functional Cardiac Measures and Response to Treatment Initiation in Patients with Systemic Light-Chain (AL) Amyloidosis: Results from a Single Site Retrospective Study. Presented at ASH 2024. Abstract 4677. 2024.