AstraZeneca advances hematology and cell therapy ambition with largest-ever presence at ASH

Investigational T-cell engager, surovatamig, and CAR T-cell therapy, AZD0120, will show potential with initial data across multiple blood cancers

New results will showcase benefit of CALQUENCE^® in patients with mantle cell lymphoma and chronic lymphocytic leukemia

New data will further support clinical benefits of ULTOMIRIS^® in paroxysmal nocturnal hemoglobinuria and its potential to improve outcomes for pediatric patients with hematopoietic stem cell transplant-associated thrombotic microangiopathy

WILMINGTON, Del.--(BUSINESS WIRE)--AstraZeneca advances its ambition to redefine hematology care with new data from its diverse pipeline and portfolio at the 67^th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6-9, 2025.

This year’s ASH congress will feature the Company’s largest presence to date, with 65 abstracts across eight approved and investigational medicines, including 15 oral presentations.

Key presentations include:

• Phase I trial of surovatamig: Updated results at three-year follow up from the ongoing first-in-human trial of surovatamig, a CD19xCD3 T-cell engager, in relapsed/refractory (R/R) follicular lymphoma (FL) (Oral Abstract #1005).
• DURGA-1 Phase Ib/II study: Initial data for AZD0120 in patients with R/R multiple myeloma (MM). AZD0120 is an investigational BCMAxCD19 chimeric antigen receptor T-cell (CAR T) therapy (Oral Abstract #269).
• ECHO Phase III trial: Results after 50 months of follow up evaluating CALQUENCE^® (acalabrutinib) plus bendamustine and rituximab in the first-line treatment of mantle cell lymphoma (MCL) (Oral Abstract #885).
• ALXN1210-TMA-314 Phase III trial: Additional results from the open-label trial evaluating ULTOMIRIS^® (ravulizumab-cwvz) in pediatric patients with hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) (Oral Abstract #1052).

Anas Younes, Senior Vice President, Hematology R&D and Chief Medical Officer, AstraZeneca, said: “We are advancing a broad pipeline of investigational therapies with the potential to redefine patient care across multiple types of blood cancer. At ASH, we are sharing meaningful progress with early efficacy and safety data for AZD0120, our first cell therapy, in multiple myeloma, and for surovatamig, a novel T-cell engager, in B-cell malignancies.”

Christophe Hotermans, Senior Vice President, Head of Global Medical Affairs, Alexion, said: “At ASH, we look forward to demonstrating how pioneering science can drive meaningful advances for people living with rare hematologic conditions. New data on ULTOMIRIS, including Phase III results in pediatric patients with HSCT-TMA, will show clinically meaningful overall survival and improved outcomes, highlighting our ongoing pursuit to realize the full potential of our medicines and their impact on treating rare conditions.”

Additional highlights include:

• SYRUS Phase I/II trial: Updated safety and efficacy data for surovatamig in adolescent and adult patients with R/R B-cell acute lymphoblastic leukemia (Abstract #3345)
• Phase I trial of surovatamig: Initial efficacy and safety data for surovatamig in R/R diffuse large B-cell lymphoma (Abstract #5514)
• AZD0120: Follow-up data from two investigator-initiated trials (IIT) in China evaluating AZD0120 as a first-line therapy in high-risk, newly diagnosed MM (Oral Abstract #258).
• TrAVeRse Phase II trial: Preliminary results evaluating CALQUENCE plus venetoclax and rituximab in treatment-naïve MCL patients (Oral Abstract #884)
• AMPLIFY Phase III trial: Exploratory analyses supporting the safety and efficacy profile of CALQUENCE in first-line chronic lymphocytic leukemia, with new subgroup data evaluating the impact of prognostic mutations on clinical outcomes (Poster Abstract #3898)
• ALPHA Phase III trial: Sub-analysis of results evaluating VOYDEYA™ (danicopan) as add-on to ULTOMIRIS or SOLIRIS^® (eculizumab) in adults with paroxysmal nocturnal hemoglobinuria (PNH) and clinically significant extravascular hemolysis, including in patients with advanced age (Oral Abstract #949)
• ULTOMIRIS: Real-world evidence highlighting the impact of ULTOMIRIS in certain patient subgroups across approved indications, including in pregnant patients (Poster Abstracts #6238 and #4458)

Key presentations during the 67^th ASH Annual Meeting and Exposition

INDICATIONS AND USAGE

CALQUENCE is a Bruton tyrosine kinase (BTK) inhibitor indicated:

• In combination with bendamustine and rituximab (BR) for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation (HSCT).
• For the treatment of adult patients with MCL who have received at least one prior therapy.
• 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 32% of 1,764 patients exposed to CALQUENCE in clinical trials, most often due to respiratory tract infections (19% of all patients, including pneumonia in 9%). These infections predominantly occurred in the absence of Grade 3 or 4 neutropenia, with neutropenic infection reported in 2.7% of all patients. Opportunistic infections in recipients of CALQUENCE have included, but are not limited to, hepatitis B virus reactivation, fungal pneumonia, Pneumocystis jirovecii 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 treated with CALQUENCE. Major hemorrhage (serious or Grade 3 or higher bleeding or any central nervous system bleeding) occurred in 4.4% of patients, with fatal hemorrhage occurring in 0.2% of 1,764 patients exposed to CALQUENCE in clinical trials. Bleeding events of any grade, excluding bruising and petechiae, occurred in 40% of patients.

Use of antithrombotic agents concomitantly with CALQUENCE may further increase the risk of hemorrhage. In clinical trials, major hemorrhage occurred in 7% of patients taking CALQUENCE without antithrombotic agents and 4% 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 to 7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Cytopenias

CALQUENCE can cause Grade 3 or 4 cytopenias. Grade 3 or 4 cytopenias included absolute neutrophil count decreased (26%), platelets decreased (10%), hemoglobin decreased (10%), and absolute lymphocyte count decreased (10%) in patients treated with CALQUENCE alone or in combination with obinutuzumab; Grade 4 neutropenia developed in 14% 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 18% of 1,764 patients exposed to CALQUENCE in clinical trials. The most frequent second primary malignancy was non-melanoma skin cancer, reported in 10% of patients, followed by other solid tumors in 9% (including melanoma, lung cancer, gastrointestinal cancers, and genitourinary cancers) and hematologic malignancies (1%). Monitor patients for the development of second cancers and advise protection from sun exposure.

Cardiac Arrhythmias

Fatal and serious cardiac arrhythmias have occurred in patients treated with CALQUENCE. Grade 3 or 4 atrial fibrillation or flutter was reported in 2.6% of 1,764 patients treated with CALQUENCE, with all grades of atrial fibrillation or flutter reported in 7% of all patients. Grade 3 or higher ventricular arrhythmia events were reported in 0.6% of patients, including fatal cases in 0.3% of all patients. The risk of arrhythmias may be increased in patients with cardiac risk factors, hypertension, previous arrhythmias, and acute infection. Monitor for symptoms of arrhythmia (e.g., palpitations, dizziness, syncope, dyspnea) and manage as appropriate.

Hepatotoxicity, Including Drug-Induced Liver Injury

Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of drug-induced liver injury (DILI), has occurred in patients treated with Bruton tyrosine kinase inhibitors, including CALQUENCE.

Evaluate bilirubin and transaminases at baseline and throughout treatment with CALQUENCE. For patients who develop abnormal liver tests after CALQUENCE, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold CALQUENCE. Upon confirmation of DILI, discontinue CALQUENCE.

ADVERSE REACTIONS

Previously Untreated Mantle Cell Lymphoma
The most common adverse reactions (≥15%) of any grade in patients with previously untreated MCL who received CALQUENCE plus BR were rash (47%), COVID-19 (38%), fatigue (37%), diarrhea (37%), pneumonia (31%), headache (31%), upper respiratory tract infection (30%), pyrexia (29%), cough (27%), vomiting (26%), constipation (25%), hemorrhage (20%), edema (20%), secondary primary malignancy (19%), dizziness (18%), arthralgia (18%), and dyspnea (17%).

Grade 4 laboratory abnormalities in >15% of patients treated with CALQUENCE plus BR include lymphocytes decreased (26%), absolute neutrophils decreased (36%), and uric acid increased (17%).

Serious adverse reactions occurred in 69% of patients who received CALQUENCE plus BR. Serious adverse reactions reported in ≥2% of patients were pneumonia (23%; includes COVID-19 pneumonia), COVID-19 (20%; includes COVID-19 pneumonia), second primary malignancy (7%), pyrexia (6%), rash (3.4%), febrile neutropenia (3.4%), atrial fibrillation (3%), sepsis (2.7%), and anemia (2.4%). Fatal adverse reactions that occurred within 30 days of the last study treatment were reported in 12% who received CALQUENCE plus BR including COVID-19 (6%; includes COVID-19 pneumonia), pneumonia (1%), second primary malignancy (0.7%), sepsis (0.3%), and pneumonitis (0.3%).

Adverse reactions led to permanent discontinuation of CALQUENCE in 43%, dosage interruptions in 74%, and dosage reductions in 10% of patients. Adverse reactions that resulted in dosage modification in >10% included infections, cytopenias, rashes, and gastrointestinal toxicity. Adverse reactions which resulted in permanent discontinuation of CALQUENCE in ≥4% of patients included COVID-19 (includes COVID-19 pneumonia) and neutropenia.

Previously Treated Mantle Cell Lymphoma
The most common adverse reactions (≥20%) of any grade in patients with relapsed or refractory MCL exposed to CALQUENCE 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.

Chronic Lymphocytic Leukemia
The most common adverse reactions (≥30%) of any grade in patients with CLL exposed to CALQUENCE 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 (2.8% to 7%).

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.

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