Positive high-level results from an interim analysis of the ECHO Phase III trial showed AstraZeneca?s CALQUENCE(acalabrutinib) in combination with standard-of-care chemoimmunotherapy, bendamustine and rituximab, demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus standard of care in previously untreated adult patients with mantle cell lymphoma (MCL). A trend was observed in favor of CALQUENCE plus chemoimmunotherapy for the secondary endpoint of overall survival (OS). The OS data were not mature at the time of this analysis and the trial will continue to assess OS.

MCL is a rare and typically aggressive form of non-Hodgkin lymphoma (NHL), often diagnosed as a late-stage disease, resulting when B-lymphocytes mutate into malignant cells within a region of the lymph node known as the mantle zone. It is estimated that there are more than 27,500 patients diagnosed with MCL worldwide. The safety and tolerability of CALQUENCE was consistent with its known safety profile, and no new safety signals were identified.

The data will be presented at a forthcoming medical meeting and shared with global regulatory authorities. As part of an extensive clinical development program, AstraZeneca is currently evaluating CALQUENCE alone and in combination for the treatment of multiple B-cell blood cancers, including chronic lymphocytic leukemia (CLL), MCL, and diffuse large B-cell lymphoma. CALQUENCE has been used to treat more than 80,000 patients worldwide and is approved for the treatment of CLL and small lymphocytic lymphoma (SLL) in the US, approved for CLL in the EU and many other countries worldwide and approved in Japan and China for relapsed or refractory CLL and SLL.

CALQUENCE is also approved in the US, China and several other countries for the treatment of adult patients with MCL who have received at least one prior therapy. CALQUENCE is not currently approved for the treatment of MCL in Japan or the EU. 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).

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 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.

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. 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, 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.