Calquence (acalabrutinib) / AstraZeneca - LARVOL DELTA

A Triple Oral Combination of Bendamustine, Acalabrutinib, and Venetoclax Demonstrates Efficacy Against Mantle Cell Lymphoma In Vitro and In Vivo. (PubMed, Cancers (Basel)) - "Background/Objectives: Bendamustine (BEN) combined with rituximab (RTX) remains a standard first-line therapy for transplant-ineligible patients with newly diagnosed mantle cell lymphoma (MCL)... Our findings support the efficacy of oral BEN as both a monotherapy and as part of an all-oral treatment regimen for MCL. These results warrant further investigation into the clinical potential of oral BEN, particularly in combination with targeted agents."

Journal • Preclinical • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • Transplantation • ANXA5

Acalabrutinib as premedication in platinum agents desensitization protocols: a case series supporting its role in enhancing tolerance with a repeatible efficacity (EAACI 2025) - "To manage breakthrough reactions occurring during desensitization, premedication strategies, including the use of omalizumab, have been documented in case series. Both patients received acalabrutinib as premedication 48h, 24h before and on the day of desensitization to platinum agents which allowed them to successfully complete subsequent chemotherapy cycles (four for the first and two for the second patient) without adverse events or organ impairment resulting from acalabrutinib. Conclusion This case series supports the potential of acalabrutinib as premedication for patients experiencing breakthrough reactions to platinum agents, allowing a sustained and safe continuation of chemotherapy."

Clinical • Immunology • IL6 • TNFA

Acalabrutinib for the Treatment of Ibrutinib-Intolerant Mantle Cell Lymphoma (clinicaltrials.gov) - P2 | N=9 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Jun 2025 ➔ Jun 2027 | Trial primary completion date: Jun 2025 ➔ Jun 2027

Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Oncology • CCND1 • CD20

NCI-2018-01182: Venetoclax With Ibrutinib or Acalabrutinib in Pts. With High-risk CLL (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Jun 2025 ➔ May 2027 | Trial primary completion date: Jun 2025 ➔ May 2027

Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • TP53

ESR-23-22182: Intermittent Versus Continuous Venetoclax With Acalabrutinib for CLL/SLL (clinicaltrials.gov) - P2 | N=62 | Not yet recruiting | Sponsor: Zulfa Omer

New P2 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

How well does acalabrutinib work and how safe is it to treat patients with chronic lymphocytic leukemia/small lymphocytic lymphoma who have had previous treatments? a plain language summary of 2 key studies. (PubMed, Future Oncol) - No abstract available

Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

CLL-Frail: Efficacy of Acalabrutinib in Very Old or Frail Patients With Treatment-naïve or Relapsed/Refractory CLL (clinicaltrials.gov) - P2 | N=53 | Completed | Sponsor: German CLL Study Group | Active, not recruiting ➔ Completed

Trial completion • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2

A Triple Oral Combination of Bendamustine, Acalabrutinib, and Venetoclax Demonstrates Efficacy Against Mantle Cell Lymphoma In Vitro and In Vivo (Multidisciplinary Digital Publishing Institute) - "BEN induced significant cytotoxicity in both cell lines at low, clinically relevant concentrations. In contrast, VEN demonstrated limited efficacy as monotherapy, with Z-138 showing sensitivity only at high doses. However, combining BEN with VEN with or without ACAL, enhanced apoptosis and cytotoxicity, with more pronounced effects in Z-138. In vivo, oral BEN significantly reduced tumor growth and prolonged survival in both xenograft models."

Preclinical • Mantle Cell Lymphoma

SOUNDTRACK-E: A phase 1/2, open-label, multicenter study to evaluate the safety and efficacy of AZD0486 monotherapy or combination therapy in patients with mature B-cell malignancies. (ASCO 2025) - P1, P1/2 | "Substudy 1 evaluates SC AZD0486 in R/R CLL/small lymphocytic lymphoma and includes a monotherapy cohort (1A; ≥2 prior lines of therapy [pLOT] with Bruton tyrosine kinase inhibitor exposure) and a cohort that receives combination with acalabrutinib (1B; ≥1 pLOT)...In substudy 3, R-CHOP is administered once every 3 weeks for 6 cycles...Secondary objectives include efficacy endpoints, pharmacokinetics, and immunogenicity. Enrollment opened in October 2024."

Clinical • Combination therapy • Monotherapy • P1/2 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • CNS Disorders • Diffuse Large B Cell Lymphoma • Epilepsy • Follicular Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Feasibility of Bruton's Tyrosine Kinase Inhibitor Discontinuation in Chronic Lymphocytic Leukemia: The Patient Perspective. (PubMed, Clin Lymphoma Myeloma Leuk) - "These data provide a unique report of patient experiences. The data suggest that BTKi may be feasible and result in a period of treatment-free remission. The data also indicate that patients are generally relieved when they anticipate BTKi discontinuation and observe significant QOL improvements after BTKi discontinuation. As such, these data should prompt prospective study of time-limited BTKi therapy for CLL."

Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Mood Disorders • Oncology • Psychiatry

Fixed-duration Calquence-based regimens approved in EU for patients with chronic lymphocytic leukaemia in the 1st-line setting (AstraZeneca Press Release) - "A fixed-duration regimen of AstraZeneca’s Calquence (acalabrutinib) in combination with venetoclax, with or without obinutuzumab, has been approved in the European Union (EU) for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL). The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and was based on positive results from the pivotal AMPLIFY Phase III trial, presented at the American Society of Hematology 2024 Annual Meeting and published in The New England Journal of Medicine."

EMA approval • Chronic Lymphocytic Leukemia

BOSS: A Study to Investigate the Sequencing Strategy of Pirtobrutinib After Disease Progression on First-line Acalabrutinib Treatment for Adult Participants With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: AstraZeneca | N=60 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Real-world comparative effectiveness of first-line Bruton tyrosine kinase inhibitors (BTKis) in patients with chronic lymphocytic leukemia (CLL). (ASCO 2025) - "In phase 3 randomized trials among pts with relapsed or refractory CLL, zanubrutinib (zanu) demonstrated superior efficacy vs ibrutinib (ibr), while acalabrutinib (acala) only showed noninferiority to ibr. Patients with zanu had significantly longer rwTTNT, rwTTD, and rwOS compared to those with ibr and longer trends compared to those with acala. Limitations include limited follow-up time for zanu vs ibr and acala."

Clinical • HEOR • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • TP53

Real-world zanubrutinib treatment patterns in mantle cell lymphoma (MCL) among US community oncology patients with prior Bruton tyrosine kinase inhibitor (BTKi) therapy. (ASCO 2025) - "The FDA has approved acalabrutinib (acala), as a single agent and in combination with bendamustine and rituximab, and zanu for treating relapsed/refractory MCL. The first-generation BTKi, ibrutinib (ibr), was voluntarily withdrawn in April 2023... In the US community setting, most patients with MCL treated with zanu who had prior ibr or acala treatment discontinued ibr or acala within 1 year. Real-world data from across the US have demonstrated the effectiveness of zanu in MCL after treatment with another BTKi. Reasons for discontinuation are still to be examined."

Clinical • Real-world • Real-world evidence • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

Real-world Bruton tyrosine kinase inhibitor (BTKi) use and clinical outcomes among patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). (ASCO 2025) - "The next-generation BTKi zanubrutinib (zanu) demonstrated superiority over the first-generation BTKi ibrutinib (ibr) in treating R/R CLL, while the second-generation BTKi acalabrutinib (acala) only showed noninferiority to ibr. In this real-world comparative effectiveness analysis in 1L CLL/SLL, patients who received zanu were significantly more likely to remain on treatment compared with those who received acala; they were also less likely to require the next LOT. Limitations include shorter follow-up time for zanu vs acala."

Clinical • Clinical data • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Real-world zanubrutinib treatment patterns in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) among US community oncology patients with prior acalabrutinib therapy. (ASCO 2025) - "Funded by BeiGene Background: Despite higher selectivity of the second-generation Bruton tyrosine kinase inhibitor (BTKi) acalabrutinib (acala) compared with the first-generation BTKi ibrutinib (ibr), a notable fraction of clinical trial patients treated with acala discontinued treatment due to adverse events. In the US community setting, most patients with CLL/SLL who received acala discontinued therapy within 1 year of initiation. After prior acala therapy, the majority of patients treated with zanu remained on treatment at data cut-off. Consistent with other real-world data from across the US, the effectiveness of zanu in CLL/SLL was demonstrated despite prior acala treatment."

Clinical • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

A real-world comparative analysis of cardiovascular (CV) safety and time to next treatment (TTNT) with acalabrutinib versus ibrutinib in treatment-naive patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). (ASCO 2025) - "In this retrospective real-world data analysis comparing acalabrutinib with ibrutinib in the first-line setting, treatment-naive patients with CLL/SLL receiving acalabrutinib had fewer CV safety events and continued to receive treatment for longer than those receiving ibrutinib."

Clinical • Real-world • Real-world evidence • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Hypertension • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

A real-world comparative study of hypertension (HTN) and time to treatment failure (TTF) with acalabrutinib versus ibrutinib in treatment-naive Medicare-eligible patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). (ASCO 2025) - "In treatment-naive Medicare-eligible patients with CLL/SLL, acalabrutinib had fewer CV events, a lower risk of new/worsening HTN, fewer discontinuations due to intolerability, and prolonged TTF versus ibrutinib."

Clinical • Medicare • Real-world • Real-world evidence • Reimbursement • US reimbursement • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Hypertension • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Risk of hypertension in patients newly diagnosed with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and treated with covalent Bruton tyrosine kinase inhibitors (cBTKi): A real-world study. (ASCO 2025) - "This real-world study shows that patients newly diagnosed with CLL/SLL treated with 1L zanubrutinib or acalabrutinib had lower rates of developing new-onset HTN compared to patients treated with 1L ibrutinib."

Clinical • Real-world • Real-world evidence • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Malignancies • Hypertension • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Comparing real-world treatment patterns and outcomes of zanubrutinib and acalabrutinib in CLL/SLL at University of California academic health centers. (ASCO 2025) - "Funded by BeiGene Background: Newer BTK inhibitors zanubrutinib (ZANU) and acalabrutinib (ACA) are preferred over first-generation ibrutinib for chronic lymphocytic leukemia (CLL) treatment due to better toxicity profiles shown in randomized controlled trials. In this RW study, ZANU was associated with a lower discontinuation risk than ACA. Poorer survival outcomes were linked to older age, more comorbidities, lower socioeconomic status, and AA patients faced higher risks of treatment discontinuation. These findings emphasize the need for further investigation into underlying causes to guide clinical decisions and optimize CLL treatment strategies in diverse RW settings."

Clinical • HEOR • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

Comparative efficacy of zanubrutinib (ZANU) versus fixed-duration acalabrutinib plus venetoclax (AV) for first-line treatment of chronic lymphocytic leukemia (CLL): A matching-adjusted indirect comparison (MAIC). (ASCO 2025) - P3 | "With the assumption of bendamustine plus rituximab (BR) and fludarabine plus cyclophosphamide and rituximab (FCR)/BR treated as common control arms, SEQUOIA and AMPLIFY can be linked through FCR/BR and the comparison of ZANU and AV were conducted in an anchored MAIC. This MAIC examined the relative efficacy of ZANU versus AV and suggested a significant PFS advantage for ZANU over AV regimen. Results should be interpreted with considerations of MAIC model assumptions. Future analyses upon trial data maturation are warranted."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • IGH • TP53

A network meta-analysis (NMA) of efficacy of zanubrutinib versus fixed-duration acalabrutinib plus venetoclax in treatment-naïve (TN) chronic lymphocytic leukemia (CLL). (ASCO 2025) - P3 | "Bendamustine plus rituximab (BR) and fludarabine plus cyclophosphamide and rituximab (FCR)/BR were assumed to be treated as common control arms in the network. This NMA found a statistically significant improvement in PFS for ZANU over AV for patients with low-risk TN CLL. The observed efficacy differences should be interpreted under the limitation and assumptions of NMA, with further analysis upon trial data maturation. *Estimates are calculated from digitalized KM curve."

Retrospective data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • IGH • TP53

Real-world treatment utilization patterns, discontinuation and healthcare resource utilization of first-line (1L) bruton tyrosine kinase inhibitor (BTKi) therapy in chronic lymphocytic leukemia (CLL): Age-related disparity. (ASCO 2025) - " A retrospective observational study using the Symphony Integrated Dataverse was conducted to identify adult CLL patients initiating a 1L BTKi (zanubrutinib [ZANU], acalabrutinib [ACA] or ibrutinib [IBR]) treatment regimen from 02/2022 and 09/2024 (index period). This real-world study demonstrated that CLL patients treated with ZANU had longer TTD, lower discontinuation rates, and less HCRU than ACA and IBR across all patients and specifically in older patients ≥65 yrs. Further studies on long-term and clinical outcomes are warranted."

Clinical • HEOR • Real-world • Real-world evidence • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Comparative efficacy of ibrutinib versus other covalent Bruton tyrosine kinase inhibitors (cBTKis) in first-line (1L) chronic lymphocytic leukemia (CLL): A matched-adjusted indirect comparison (MAIC). (ASCO 2025) - P3 | "Funded by Pharmacyclics LLC, an AbbVie Company Background: Ibrutinib (ibr), acalabrutinib (acala), and zanubrutinib (zanu) are cBTKis approved for treatment of CLL, with demonstrated efficacy as a single-agent in 1L CLL treatment. This is the first MAIC analysis to compare long-term efficacy outcomes across cBTKis in the 1L treatment of CLL. In the absence of head-to-head 1L CLL trials, our results suggest that ibr provides similar efficacy outcomes to acala and zanu. Further analyses are needed to understand if cBTKis provide similar or different efficacy in specific pt populations, such as those with high-risk disease."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • B2M • TP53

Differential cardiotoxicity of acalabrutinib versus chemoimmunotherapy in chronic lymphocytic leukemia: A retrospective cohort study from 2000-2025 using TriNetX database. (ASCO 2025) - "The use of acalabrutinib in patients with CLL was associated with statistically significant better safety profile, with lesser risk of mortality, bleeding events and atrial fibrillation. Clinicians may consider using acalabrutinib as a superior treatment modality in the treatment of CLL. Further research maybe required to optimize treatment protocols in the best interest of patients."

Retrospective data • Atrial Fibrillation • Cardiovascular • Chronic Lymphocytic Leukemia • Congestive Heart Failure • Heart Failure • Hematological Malignancies • Hypertension • Leukemia • Oncology