CALQUENCE real-world evidence and long-term follow-up data, as well as research collaborations, will reinforce efficacy and safety across B-cell malignancies
Early clinical data will illustrate potential of multiple pipeline molecules, including TNB-486 (AZD0486), across hematologic malignancies
Research from Alexion, AstraZeneca Rare Disease, offers new insights to accelerate innovation and improve time to diagnosis for several rare diseases
WILMINGTON, Del.–(BUSINESS WIRE)–AstraZeneca will present 47 abstracts showcasing new data from across its hematology portfolio and clinical pipeline, demonstrating its commitment to redefining care for hard-to-treat blood diseases at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition, December 10 to 13, 2022.
A total of eight approved and potential new medicines will be featured across more than 10 types of blood cancers and rare diseases, including data in chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS) and amyloid light chain (AL) amyloidosis.
Anas Younes, Senior Vice President, Oncology R&D, AstraZeneca, said: “At this year’s ASH Annual Meeting, our data demonstrate the broad potential of our hematology pipeline and the continued strength of our approved medicines. Data are being highlighted from many of our early-stage molecules, including clinical trials of TNB-486 (AZD0486), a B-cell targeting T-cell engager, and presentations of long-term follow-up data will show the consistent safety and efficacy profile of CALQUENCE.”
Gianluca Pirozzi, Senior Vice President, Head of Development and Safety, Alexion, AstraZeneca Rare Disease said: “The depth and breadth of Alexion data at this year’s ASH Annual Meeting reinforce the importance of earlier diagnosis and disease management for rare diseases that are often not well-understood. We will share research across several therapy areas – including an oral presentation demonstrating the potential of vemircopan, an investigational, second-generation factor D inhibitor as monotherapy treatment of paroxysmal nocturnal hemoglobinuria – underscoring our leadership and unwavering commitment to driving critical innovations in rare disease.”
CALQUENCE® (acalabrutinib) real-world evidence and long-term follow-up data support consistent efficacy and safety profile
- A post-hoc safety analysis from the head-to-head ELEVATE-RR Phase III trial of CALQUENCE versus ibrutinib will further support tolerability differences of CALQUENCE in relapsed or refractory CLL.1
- Final long-term follow-up results of the Phase I/II trials evaluating CALQUENCE monotherapy in front-line and relapsed or refractory CLL will further support the continued efficacy and safety CALQUENCE demonstrated in both settings.2,3
- An oral presentation of Phase II research sponsored by the Dana-Farber Cancer Institute will show the efficacy and tolerability of CALQUENCE combined with venetoclax and obinutuzumab in a front-line, high-risk CLL population.4
- A retrospective pooled analysis will show the benefit of adding obinutuzumab to CALQUENCE in the front-line CLL setting in patients with select genomic characteristics.5
- An oral presentation of preliminary Phase II results sponsored by Weill Cornell Medicine will show that CALQUENCE combined with lenalidomide and rituximab is generally well-tolerated, highly effective and produces high rates of minimal residual disease-negative complete remission in front-line MCL.6
Novel treatment strategies with emerging pipeline molecules exhibit therapeutic potential
- An oral presentation of interim Phase I results evaluating TNB-486 (AZD0486), a CD19/CD3 next generation bispecific T-cell engager, will show the potential of targeting CD19/CD3, leading to an increase in anti-cancer activity in heavily pretreated patients with B-cell non-Hodgkin lymphoma (NHL).7
- Results from Phase I and II trials of CDK9 inhibitor AZD4573 alone and with CALQUENCE will exhibit data on tolerability across a broad range of hematologic malignancies, including relapsed or refractory DLBCL.8,9
- Preliminary results from an ongoing Phase I trial will demonstrate that Bcl-2/Bcl-xl inhibitor AZD0466 has been well-tolerated in patients with advanced hematologic malignancies.10
Innovating to help address the treatment needs of all patients with PNH
- An oral presentation detailing interim results from a Phase II open-label trial of vemircopan (ALXN2050) will highlight efficacy and safety data from the treatment-naïve patient group, establishing proof-of-concept as a monotherapy for PNH.11
- An interim analysis from an ongoing Phase IV trial assessing the impact of switching to standard, weight-based intravenous (i.v.) ULTOMIRIS® (ravulizumab-cwvz) from high-dose i.v. SOLIRIS® (eculizumab) in adults with PNH will be presented.12
Improving diagnosis and management of life-threatening rare diseases
- An analysis of data from the Global aHUS Registry, which contains information on patients across more than 100 sites in more than 20 countries, will highlight the importance of considering aHUS as a diagnosis even in the presence of a triggering condition or associated event.13
- An analysis of real-world patient data from the US Premier Healthcare Database will expand on the potential of the PLASMIC scoring system to aid in identifying people with aHUS and making earlier treatment decisions.14
- An analysis of pediatric patients with hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) will provide insights on the correlation between complement activation and endothelial damage in HSCT-TMA and the potential for useful biomarkers indicative of this damage to inform diagnosis.15
- Results through one year on safety, tolerability and biomarker data will be presented from a Phase II trial evaluating CAEL-101, a potentially first-in-class monoclonal antibody, in adults with AL amyloidosis.16
- A real-world analysis in a current population with AL amyloidosis using Komodo Health US claims data will highlight the need for greater awareness and understanding to accelerate time to diagnosis.17
Key presentations during the 64th ASH Annual Meeting and Exposition
|
Lead author |
Abstract title |
Presentation details |
|
CALQUENCE (acalabrutinib) |
|
|
|
Byrd, J |
Final Results of the Phase 1/2 Study of Acalabrutinib Monotherapy in Treatment-Naive Chronic Lymphocytic Leukemia with >6 Years of Follow-Up |
Abstract # 4431 Poster Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster III December 12, 2022 18:00-20:00 CST Location: Hall D (Ernest N. Morial Convention Center) |
|
Davids, MS |
Contribution of Obinutuzumab to Acalabrutinib Therapy in Patients with Treatment-Naive Chronic Lymphocytic Leukemia: Analysis of Survival Outcomes by Genomic Features |
Abstract # 1815 Poster Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster I December 10, 2022 17:30-19:30 CST Location: Hall D (Ernest N. Morial Convention Center) |
|
Davies, AJ |
Durable Responses from Acalabrutinib in Combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone (R-CHOP) as First Line Therapy for Patients with Diffuse Large B-Cell Lymphoma (DLBCL): The ACCEPT Phase Ib/II Single Arm Study |
Abstract # 4265 Poster Session: 626. Aggressive Lymphomas: Prospective Therapeutic Trials: Poster III December 12, 2022 18:00-20:00 CST Location: Hall D (Ernest N. Morial Convention Center) |
|
Furman, R |
Phase 1/2 Study of Acalabrutinib Monotherapy in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Final Results with >4 Years of Follow-Up |
Abstract # 4434 Poster Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster III December 12, 2022 18:00-20:00 CST Location: Hall D (Ernest N. Morial Convention Center) |
|
Ruan, J |
Phase 2 Trial of Acalabrutinib-Lenalidomide-Rituximab (ALR) with Real-Time Monitoring of MRD in Patients with Treatment-Naïve Mantle Cell Lymphoma |
Abstract # 73 Oral Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological I December 10, 2022 9:30 CST Location: La Nouvelle Orleans Ballroom C (Ernest N. Morial Convention Center) |
|
Ryan, CE |
Updated Results from a Multicenter, Phase 2 Study of Acalabrutinib, Venetoclax, Obinutuzumab (AVO) in a Population of Previously Untreated Patients with CLL Enriched for High-Risk Disease |
Abstract # 344 Oral Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Targeted Triplet Combinations and Richter’s Transformation December 10, 2022 16:15 CST Location: R06-R09 (Ernest N. Morial Convention Center) |
|
Seymour, JF |
Assessing the Burden of Adverse Events in a Head-to-Head Trial of Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia (CLL) |
Abstract # 3133 Poster Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster II December 11, 2022 18:00-20:00 CST Location: Hall D (Ernest N. Morial Convention Center) |
|
AZD0486 (CD19/CD3 T-cell engager) |
|
|
|
Hou, JZ |
Interim Results of the Phase 1 Study of Tnb-486, a Novel CD19xCD3 T-Cell Engager, in Patients with Relapsed/Refractory (R/R) B-NHL |
Abstract # 612 Oral Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological IV December 11, 2022 17:45 CST Location: 278-282 (Ernest N. Morial Convention Center) |
|
AZD0466 (Bcl-2/Bcl-xL inhibitor) |
||
|
Arslan, S |
Safety and Tolerability of AZD0466 as Monotherapy for Patients with Advanced Hematological Malignancies. Preliminary Results from an Ongoing Phase I/II Trial |
Abstract # 4094 Poster Session: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster III December 12, 2022 18:00-20:00 CST Location: Hall D (Ernest N. Morial Convention Center) |
|
AZD4573 (CDK9 inhibitor) |
||
|
Brümmendorf, T |
Safety, Tolerability, Pharmacokinetics (PK) and Preliminary Antitumor Activity of the Cyclin-Dependent Kinase-9 (CDK9) Inhibitor AZD4573 in Relapsed/Refractory Hematological Malignancies: A Phase 1 First-in-Human Study |
Abstract # 1353 Poster Session: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster I December 10, 2022 17:30-19:30 CST Location: Hall D (Ernest N. Morial Convention Center) |
|
Strati, P |
Phase 1b/2a Study of AZD4573 (CDK9i) and Acalabrutinib in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (r/r DLBCL): Results from Dose-Escalation |
Abstract # 2962 Poster Session: 627. Aggressive Lymphomas: Clinical and Epidemiological: Poster II December 11, 2022 18:00-20:00 CST Location: Hall D (Ernest N. Morial Convention Center) |
|
VEMIRCOPAN (ALXN2050) |
|
|
|
Browett, P
|
Vemircopan (ALXN2050) Monotherapy in Paroxysmal Nocturnal Hemoglobinuria: Interim Data from a Phase 2 Open-Label Proof-of-Concept Study |
Abstract # 294 Oral Session: 508. Bone Marrow Failure: Acquired: Clinical Studies December 10, 2022 17:15 CST Location: 260-262 (Ernest N. Morial Convention Center) |
|
ULTOMIRIS (ravulizumab-cwvz) |
||
|
Griffin, M
|
Terminal Complement Inhibition and Control of Hemolysis in Paroxysmal Nocturnal Hemoglobinuria Following Switching from High-Dose Eculizumab to Ravulizumab: An Interim Analysis |
Abstract # 1251 Poster Session: 508. Bone Marrow Failure: Acquired: Poster I December 10, 2022 17:30-19:30 CST Location: Hall D (Ernest N. Morial Convention Center) |
|
ALXN1820 |
||
|
Dai, Y
|
A Phase 2a, Randomized, Open-Label Study to Evaluate Multiple Dosing Regimens of Subcutaneous ALXN1820 in Adult Patients with Sickle Cell Disease |
Abstract # 3713 Poster Session: 114. Hemoglobinopathies, Excluding Thalassemia: Clinical and Epidemiological: Poster III December 12, 2022 18:00-20:00 CST Location: Hall D (Ernest N. Morial Convention Center) |
|
CAEL-101 |
||
|
Valent, J |
1-Year Results from a Phase 2 Study to Determine Safety and Tolerability of Treating Patients with Light-Chain (AL) Amyloidosis with CAEL-101, an Anti-Amyloid Monoclonal Antibody, Combined with Anti-Plasma Cell Dyscrasia |
Abstract # 4550 Poster Session: 653. Myeloma and Plasma Cell Dyscrasias: Prospective Therapeutic Trials: Poster III December 12, 2022 18:00-20:00 CST Location: Hall D (Ernest N. Morial Convention Center) |
|
AL Amyloidosis |
||
|
Catini, J |
Evaluation of the Path to Diagnosis and Time to Treatment in Patients with Light-Chain Amyloidosis Using the Komodo Claims Database |
Abstract # 1887 Poster Session: 652. Multiple Myeloma and Plasma Cell Dyscrasias: Clinical and Epidemiological: Poster I December 10, 2022 17:30-19:30 CST Location: Hall D (Ernest N. Morial Convention Center) |
|
HSCT-TMA |
||
|
Jacobi, P |
Complement Activation is Associated with Endothelial Damage in Hematopoietic Stem Cell Transplant Associated-Thrombotic Microangiopathy |
Abstract # 2431 Poster Session: 301. Vasculature, Endothelium, Thrombosis and Platelets: Basic and Translational: Poster II December 11, 2022 18:00-20:00 CST Location: Hall D (Ernest N. Morial Convention Center) |
|
aHUS |
||
|
Gasteyger, C
|
Use of PLASMIC Scores to Aid Diagnosis of aHUS: A Real-World Analysis of Hospitalized Patients from the Premier Healthcare Database |
Abstract # 1178 Poster Session: 331. Thrombotic Microangiopathies/Thrombocytopenias and COVID-19-related Thrombotic/Vascular Disorders: Clinical and Epidemiological: Poster I December 10, 2022 17:30-19:30 CST Location: Hall D (Ernest N. Morial Convention Center) |
|
Siedlecki, A
|
Characterization of Patients with aHUS and Triggering/Associated Events, with and without Complement Pathogenic Variants or anti-CFH Antibodies: A Global aHUS Registry Analysis |
Abstract # 1173 Poster Session: 331. Thrombotic Microangiopathies/Thrombocytopenias and COVID-19-related Thrombotic/Vascular Disorders: Clinical and Epidemiological: Poster I December 10, 2022 17:30-19:30 CST Location: Hall D (Ernest N. Morial Convention Center) |
INDICATION AND USAGE
CALQUENCE is a Bruton tyrosine kinase (BTK) inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
CALQUENCE is also indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
IMPORTANT SAFETY INFORMATION ABOUT CALQUENCE® (acalabrutinib) tablets
Serious and Opportunistic Infections
Fatal and serious infections, including opportunistic infections, have occurred in patients with hematologic malignancies treated with CALQUENCE.
Serious or Grade 3 or higher infections (bacterial, viral, or fungal) occurred in 19% of 1029 patients exposed to CALQUENCE in clinical trials, most often due to respiratory tract infections (11% of all patients, including pneumonia in 6%). These infections predominantly occurred in the absence of Grade 3 or 4 neutropenia, with neutropenic infection reported in 1.9% of all patients. Opportunistic infections in recipients of CALQUENCE have included, but are not limited to, hepatitis B virus reactivation, fungal pneumonia, Pneumocystis jiroveci pneumonia, Epstein-Barr virus reactivation, cytomegalovirus, and progressive multifocal leukoencephalopathy (PML). Consider prophylaxis in patients who are at increased risk for opportunistic infections. Monitor patients for signs and symptoms of infection and treat promptly.
Hemorrhage
Fatal and serious hemorrhagic events have occurred in patients with hematologic malignancies treated with CALQUENCE. Major hemorrhage (serious or Grade 3 or higher bleeding or any central nervous system bleeding) occurred in 3.0% of patients, with fatal hemorrhage occurring in 0.1% of 1029 patients exposed to CALQUENCE in clinical trials. Bleeding events of any grade, excluding bruising and petechiae, occurred in 22% of patients.
Use of antithrombotic agents concomitantly with CALQUENCE may further increase the risk of hemorrhage. In clinical trials, major hemorrhage occurred in 2.7% of patients taking CALQUENCE without antithrombotic agents and 3.6% of patients taking CALQUENCE with antithrombotic agents. Consider the risks and benefits of antithrombotic agents when co-administered with CALQUENCE. Monitor patients for signs of bleeding.
Consider the benefit-risk of withholding CALQUENCE for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.
Cytopenias
Grade 3 or 4 cytopenias, including neutropenia (23%), anemia (8%), thrombocytopenia (7%), and lymphopenia (7%), developed in patients with hematologic malignancies treated with CALQUENCE. Grade 4 neutropenia developed in 12% of patients. Monitor complete blood counts regularly during treatment. Interrupt treatment, reduce the dose, or discontinue treatment as warranted.
Second Primary Malignancies
Second primary malignancies, including skin cancers and other solid tumors, occurred in 12% of 1029 patients exposed to CALQUENCE in clinical trials. The most frequent second primary malignancy was skin cancer, reported in 6% of patients. Monitor patients for skin cancers and advise protection from sun exposure.
Atrial Fibrillation and Flutter
Grade 3 atrial fibrillation or flutter occurred in 1.1% of 1029 patients treated with CALQUENCE, with all grades of atrial fibrillation or flutter reported in 4.1% of all patients. The risk may be increased in patients with cardiac risk factors, hypertension, previous arrhythmias, and acute infection. Monitor for symptoms of arrhythmia (eg, palpitations, dizziness, syncope, dyspnea) and manage as appropriate.
ADVERSE REACTIONS
The most common adverse reactions (≥20%) of any grade in patients with relapsed or refractory MCL were anemia,* thrombocytopenia,* headache (39%), neutropenia,* diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%). The most common Grade ≥3 non-hematological adverse reaction (reported in at least 2% of patients) was diarrhea (3.2%).
*Treatment-emergent decreases (all grades) of hemoglobin (46%), platelets (44%), and neutrophils (36%) were based on laboratory measurements and adverse reactions.
Dose reductions or discontinuations due to any adverse reaction were reported in 1.6% and 6.5% of patients, respectively. Increases in creatinine to 1.5 to 3 times the upper limit of normal (ULN) occurred in 4.8% of patients.
The most common adverse reactions (≥30%) of any grade in patients with CLL were anemia,* neutropenia,* thrombocytopenia,* headache, upper respiratory tract infection, and diarrhea.
*Treatment-emergent decreases (all grades) of hemoglobin, platelets, and neutrophils were based on laboratory measurements and adverse reactions.
In patients with previously untreated CLL exposed to CALQUENCE, fatal adverse reactions that occurred in the absence of disease progression and with onset within 30 days of the last study treatment were reported in 2% for each treatment arm, most often from infection. Serious adverse reactions were reported in 39% of patients in the CALQUENCE plus obinutuzumab arm and 32% in the CALQUENCE monotherapy arm, most often due to events of pneumonia (7% and 2.8%, respectively).
Adverse reactions led to CALQUENCE dose reduction in 7% and 4% of patients in the CALQUENCE plus obinutuzumab arm (N=178) and CALQUENCE monotherapy arm (N=179), respectively. Adverse events led to discontinuation in 11% and 10% of patients, respectively. Increases in creatinine to 1.5 to 3 times ULN occurred in 3.9% and 2.8% of patients in the CALQUENCE combination arm and monotherapy arm, respectively.
In patients with relapsed/refractory CLL exposed to CALQUENCE, serious adverse reactions occurred in 29% of patients. Serious adverse reactions in >5% of patients who received CALQUENCE included lower respiratory tract infection (6%). Fatal adverse reactions within 30 days of the last dose of CALQUENCE occurred in 2.6% of patients, including from second primary malignancies and infection.
Adverse reactions led to CALQUENCE dose reduction in 3.9% of patients (N=154), dose interruptions in 34% of patients, most often due to respiratory tract infections followed by neutropenia, and discontinuation in 10% of patients, most frequently due to second primary malignancies followed by infection. Increases in creatinine to 1.5 to 3 times ULN occurred in 1.3% of patients who received CALQUENCE.
DRUG INTERACTIONS
Strong CYP3A Inhibitors: Avoid co-administration of CALQUENCE with a strong CYP3A inhibitor. If these inhibitors will be used short-term, interrupt CALQUENCE. After discontinuation of strong CYP3A inhibitor for at least 24 hours, resume previous dosage of CALQUENCE.
Moderate CYP3A Inhibitors: Reduce the dosage of CALQUENCE to 100 mg once daily when co-administered with a moderate CYP3A inhibitor.
Strong CYP3A Inducers: Avoid co-administration of CALQUENCE with a strong CYP3A inducer. If co-administration is unavoidable, increase the dosage of CALQUENCE to 200 mg approximately every 12 hours.
SPECIFIC POPULATIONS
Based on findings in animals, CALQUENCE may cause fetal harm and dystocia when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. Advise pregnant women of the potential risk to a fetus.
Pregnancy testing is recommended for females of reproductive potential prior to initiating CALQUENCE therapy. Advise female patients of reproductive potential to use effective contraception during treatment with CALQUENCE and for 1 week following the last dose of CALQUENCE.
It is not known if CALQUENCE is present in human milk. Advise lactating women not to breastfeed while taking CALQUENCE and for 2 weeks after the last dose.
Avoid use of CALQUENCE in patients with severe hepatic impairment (Child-Pugh class C). No dosage adjustment of CALQUENCE is recommended in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment.
Please see full Prescribing Information, including Patient Information.
INDICATION(S) & IMPORTANT SAFETY INFORMATION for ULTOMIRIS
INDICATION(S)
Paroxysmal Nocturnal Hemoglobinuria (PNH)
ULTOMIRIS is indicated for the treatment of adult and pediatric patients one month of age and older with paroxysmal nocturnal hemoglobinuria (PNH).
Atypical Hemolytic Uremic Syndrome (aHUS)
ULTOMIRIS is indicated for the treatment of adult and pediatric patients one month of age and older with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA).
Limitation of Use:
ULTOMIRIS is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).
Subcutaneous Use in Adult Patients with PNH or aHUS
Subcutaneous administration of ULTOMIRIS is not approved for use in pediatric patients.
IMPORTANT SAFETY INFORMATION
|
WARNING: SERIOUS MENINGOCOCCAL INFECTIONS Life-threatening meningococcal infections/sepsis have occurred in patients treated with ULTOMIRIS. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early.
Because of the risk of serious meningococcal infections, ULTOMIRIS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called ULTOMIRIS REMS. |
Contacts
Media Inquiries
Brendan McEvoy, +1 302 885 2677
Miranda Kulp, +1 302 885 2677
US Media Mailbox: usmediateam@astrazeneca.com