Calquence (acalabrutinib) / AstraZeneca - LARVOL DELTA

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) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Real-world • Real-world evidence • Cardiovascular • 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) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

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 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) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Medicare • Real-world • Real-world evidence • Reimbursement • US reimbursement • 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) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

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) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

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

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) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Retrospective data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Differential cardiotoxicity of acalabrutinib versus chemoimmunotherapy in chronic lymphocytic leukemia: A retrospective cohort study from 2000-2025 using TriNetX database. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Retrospective data • Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

BRUIN-MCL-321: Study of BTK Inhibitor LOXO-305 Versus Approved BTK Inhibitor Drugs in Patients With Mantle Cell Lymphoma (MCL) (clinicaltrials.gov) - P3 | N=500 | Recruiting | Sponsor: Loxo Oncology, Inc. | Active, not recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

Zanubrutinib (zanu) overcomes BTK V416L resistance in B cell lymphoma models (AACR 2025) - "Introduction: The second-generation BTK inhibitors (BTKis), e.g., zanu, acalabrutinib (acala), have further transformed the therapy landscape of chronic lymphocytic leukemia (CLL)...Non-covalent BTKi e.g., pirtobrutinib (pirto) can overcome C481 mutations, but is susceptible to other BTK mutations like the recently described kinase impaired V416L and L528W mutations, which both maintain downstream signaling... These data demonstrate that zanu retains potent antitumor activity against TMD8 cells expressing BTK V416L, whereas acala and pirto may be attenuated by steric clashes. Thus, we hypothesize that clonal expansion of V416L is less likely to occur in patients with CLL treated with zanu, whereas it may lead to resistance in patients treated with acala or pirto. This hypothesis should be validated in clinical studies."

B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) in BTKi-treated mantle cell lymphoma (AACR 2025) - P2 | "Here, we explored which biomarkers might be associated with resistance to acalabrutinib, a second generation BTKi, by analyzing samples from MCL patients who were on treatment or progressed on acalabrutinib from the ACE-LY-004 study (NCT02213926), as well as using a pre-clinical MCL cell line model...It was previously attributed to a bypass resistance mechanism to first generation BTKi ibrutinib (Zhang et al., 2019)...To assess potential therapeutic implications of decreased surface expression of ROR1 in MCL post BTKi treatment, we assessed activity of a ROR1-targeted ADC (Zilovertamab vedotin; Wang et al., 2021) in BTKi-R cells...These preliminary results highlight the possible association between ROR1 expression on MCL tumor cells and BTKi response. To further dissect the interplay between ROR1 and second generation/reversible BTKi treatment in MCL, studies utilizing a multi-omics integration approach, BTKi-R MCL cell lines, and ex vivo propagated MCL patient cell..."

B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD5 • ROR1

BTK inhibitors reshape tumor transcriptome and lymph node microenvironment in CLL (AACR 2025) - "We evaluated the effects of BTKis on CLL cell transcriptome and the composition of the tumor microenvironment (TME) in CLL.Lymph node (LN) biopsies from 65 patients treated with ibrutinib (n=35) collected pre-treatment and at 24 and 72 hours from first dose or acalabrutinib (n=30) collected pre-treatment and after 3 days of treatment at 4, 12, 24, and 36 hours from the last dose of drug were submitted for RNA sequencing. The virtually immediate impact on tumor transcriptomes was paralleled by equally rapid if slightly delayed reorganization of the TME. These data suggest that the effects of BTKis spread beyond the immediate drug target and disrupt the tumor-supportive TME."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • CD4 • HIF1A • KRAS

ARV-393, a PROTAC B-cell lymphoma 6 (BCL6) degrader, combined with biologics or small molecule inhibitors (SMIs) induces tumor regressions in diffuse large B-cell lymphoma (DLBCL) models (AACR 2025) - P1 | "For example, CREBBP/EP300 and BCL6 have opposing transcriptional activities and BCL6 degradation may prevent CD20 downregulation by restoring CREBBP/EP300 chromatin access, supporting combination with anti-CD20 biologics; cooperation of EZH2 with the BCL6 repressor complex supports combining with tazemetostat (taz). Thus, we assessed the activity of ARV-393 in combination with biologics or SMIs based on potential complementary mechanistic roles.ARV-393 was administered in combination with clinically relevant doses of the standard of care (SOC) biologics rituximab, tafasitamab (tafa) and polatuzumab to mice bearing SU-DHL-4 CDX, representing a high-grade B-cell lymphoma (HGBCL, with MYC, BCL2 and BCL6 rearrangements). ARV-393 was also combined with investigational SMIs of EZH2 (taz), BCL2 (venetoclax) and BTK (acalabrutinib), in HGBCL or aggressive CDX models SU-DHL-6 (EZH2mut), OCI-Ly1 (BCL2+) and activated B-cell (ABC)-like OCI-Ly10 (MYD88 mut),..."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Oncology • BCL2 • BCL6 • CREBBP • EP300 • MYC • MYD88

CFON-026 is a macrocycle that disrupts the BTK protein scaffold thereby inhibiting all clinically relevant BTK resistance mutations (AACR 2025) - "The first generation BTK inhibitors bind covalently to Cys481 and include ibrutinib, acalabrutinib and zanubrutinib...Pirtobrutinib was developed as a second generation non-covalent BTK inhibitor, though resistance has emerged via the acquisition of BTK mutant variants BTKT474I and BTKL528W...CFON-026 disrupts the BTK kinase structure, abrogating both kinase activity and scaffold functions. CFON-026 can overcome resistance mutations emerging from all existing covalent and non-covalent BTK inhibitor therapies."

Clinical • Oncology

Acalabrutinib as premedication in platinum agents desensitization protocols: a case series supporting its role in enhancing tolerance with a repeatible efficacity (EAACI 2025) - No abstract available

Clinical • Immunology

Comparative efficacy of Bruton tyrosine kinase inhibitors in high-risk relapsed/refractory CLL: a network meta-analysis. (PubMed, Blood Adv) - "Bayesian NMAs found zanubrutinib to be the most efficacious treatment for high-risk patients, with significantly reduced risk of progression or death compared with ibrutinib (hazard ratio [95% credible interval (CrI)]: 0.49 [0.31, 0.78]), acalabrutinib (0.55 [0.32, 0.94]), and bendamustine + rituximab or idelalisib + rituximab (BR/IR) (0.12 [0.05, 0.26]). Rates of response also demonstrated trends favoring zanubrutinib compared to acalabrutinib, with significant results compared to ibrutinib. The NMA suggests that the most efficacious BTKi for patients with high-risk R/R CLL is zanubrutinib."

Journal • Retrospective data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • TP53

MAINTENANCE THERAPY POST ANTI CD19 CHIMERIC ANTIGEN RECEPTOR(CAR) T CELL THERAPY – A SINGLE CENTRE PILOT STUDY (EBMT 2025) - "Few studies have explored the options of using maintenance with 6 Mercaptopurine (6 MP) for B ALL and Acalabrutinib for B NHL after CAR T as a consolidation strategy to reduce relapse risk.We report our single center experience on the use of maintenance therapy post CAR T and the feasibility and safety of this approach...For B cell ALL, 6 MP was given in a dose targeting myelosuppression with white cell count of 1500 to 3000/microliter except 1 patient with Philadelphia positive with T315I mutation who was given Ponatinib and for B cell NHL, Acalabrutinib was started at dose of 100mg once daily and increased as per tolerance... We found in our study that maintenance therapy after CAR T cell is low cost with acceptable safety profile. Longer follow up is required before its wider applicability and consideration as a feasible choice for consolidation in these high risk individuals."

Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Non-Hodgkin Lymphoma • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology

AMPLIFY: A second-generation BTK inhibitor for fixed-duration therapy in chronic lymphocytic leukemia. (PubMed, Med) - "Recent advancements in chronic lymphocytic leukemia (CLL) treatment emphasize fixed-duration (FD) strategies, notably venetoclax with obinutuzumab or ibrutinib, now endorsed by ESMO guidelines. The AMPLIFY phase 3 trial highlights acalabrutinib-venetoclax combinations, demonstrating superior progression-free survival and manageable safety.1 These findings support FD regimens as a paradigm shift, optimizing efficacy, safety, and patient convenience in frontline CLL therapy."

Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

High lymphocyte count and bleeding risk in patients with chronic lymphocytic leukemia treated with Bruton's tyrosine kinase inhibitors. (PubMed, Wien Klin Wochenschr) - "A total of 108 CLL patients treated with BTKi (ibrutinib, n = 86, acalabrutinib, n = 22) were included. This study provides an important signal regarding the higher risk of bleeding in CLL patients treated with BTKi who present with higher ALC and higher CIRS. Further studies are needed to validate our findings and to unravel the exact pathophysiological mechanisms behind this interesting observation."

Clinical • Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

“Extension of indication to include CALQUENCE as monotherapy for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy based on final results from study ACE-LY-004 (D8225C00002)…as a consequence, sections 4.1 and 5.1 of the SmPC are updated. The Package Leaflet is updated in accordance. Version 7 of the RMP has also been submitted.” (European Medicines Agency) - Pharmacovigilance Risk Assessment Committee (PRAC) Minutes of meeting on 10 – 13 Feb 2025

PRAC • Hematological Malignancies • Mantle Cell Lymphoma • Oncology

AZD4573 in Novel Combinations With Anti-cancer Agents in Patients With Advanced Blood Cancer (clinicaltrials.gov) - P1/2 | N=40 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Oncology

Acalabrutinib-Obinutuzumab Improves Survival vs Chemoimmunotherapy in treatment-naive CLL in the 6-year Follow-up of ELEVATE-TN. (PubMed, Blood) - P3 | "Rates of AEs, serious AEs, and events of clinical interest were similar between acalabrutinib-containing arms and consistent with the known safety profiles of acalabrutinib and obinutuzumab. Efficacy and safety of acalabrutinib-containing arms were maintained, with longer PFS in both acalabrutinib arms vs chlorambucil-obinutuzumab including in patients with high-risk features."

IO biomarker • Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • IGH • TP53

CARAMEL: Acalabrutinib and Rituximab in Previously Untreated Mantle Cell Lymphoma (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: University College, London | Not yet recruiting ➔ Recruiting | N=26 ➔ 48 | Trial completion date: May 2026 ➔ Dec 2028 | Trial primary completion date: May 2026 ➔ Nov 2026

Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • Geriatric Disorders • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • CCND1

BRUIN-MCL-321: Study of BTK Inhibitor LOXO-305 Versus Approved BTK Inhibitor Drugs in Patients With Mantle Cell Lymphoma (MCL) (clinicaltrials.gov) - P3 | N=500 | Active, not recruiting | Sponsor: Loxo Oncology, Inc. | Trial completion date: Jul 2026 ➔ Apr 2028 | Trial primary completion date: Dec 2025 ➔ Jan 2027

Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology

“Extension of indication to include…in combination with venetoclax with or without obinutuzumab for the treatment of adult patients with previously untreated chronic lymphocytic leukemia (CLL), based on interim results from study AMPLIFY (D8221C00001)…as a consequence, sections 4.1, 4.2, 4.4, 4.8, and 5.1 of the SmPC are updated.” (European Medicines Agency) - Pharmacovigilance Risk Assessment Committee (PRAC)-Draft agenda for the meeting on 7 - 10 Apr 2025: “For adoption of PRAC RMP AR, PRAC RMP assessment overview and advice to CHMP”

PRAC • Chronic Lymphocytic Leukemia • Hematological Malignancies • Oncology

Acalabrutinib and Obinutuzumab for the Treatment of Previously Untreated Follicular Lymphoma or Other Indolent Non-Hodgkin Lymphomas (clinicaltrials.gov) - P2 | N=49 | Recruiting | Sponsor: Emory University | Trial primary completion date: Jan 2025 ➔ Sep 2025

Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia