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PurposeZanubrutinib is a potent, irreversible next-generation Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target kinase inhibition. We hypothesized that complete/sustained BTK occupancy may improve efficacy outcomes and increased BTK specificity may minimize off-target inhibition-related toxicities.Patients and methodsALPINE (ClinicalTrials.gov identifier: NCT03734016) is a global, randomized, open-label phase III study of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia. The primary end point was investigator-assessed overall response rate (ORR). The preplanned interim analysis was scheduled approximately 12 months after the first 415 patients were enrolled.ResultsBetween November 1, 2018, and December 14, 2020, 652 patients were enrolled. We present the interim analysis of the first 415 enrolled patients randomly assigned to receive zanubrutinib (n = 207) or ibrutinib (n = 208). At 15 months of median follow-up, ORR (partial or complete response) was significantly higher with zanubrutinib (78.3%; 95% CI, 72.0 to 83.7) versus ibrutinib (62.5%; 95% CI, 55.5 to 69.1; two-sided P < .001). ORR was higher with zanubrutinib versus ibrutinib in subgroups with del(17p)/TP53 mutations (80.5% v 50.0%) and del(11q) (83.6% v 69.1%); 12-month progression-free survival in all patients was higher with zanubrutinib (94.9%) versus ibrutinib (84.0%; hazard ratio, 0.40; 95% CI, 0.23 to 0.69). Atrial fibrillation rate was significantly lower with zanubrutinib versus ibrutinib (2.5% v 10.1%; two-sided P = .001). Rates of cardiac events, major hemorrhages, and adverse events leading to treatment discontinuation/death were lower with zanubrutinib.ConclusionZanubrutinib had a significantly higher ORR, lower atrial fibrillation rate, and improved progression-free survival and overall cardiac safety profile versus ibrutinib. These data support improved efficacy/safety outcomes with selective BTK inhibition.

Background Neutropenic sepsis frequently requires admission to an intensive care unit (ICU). Differences between subgroups of patients with neutropenic sepsis are not well characterized. Aims To investigate clinical outcomes among patients with neutropenic sepsis and hematological malignancy, metastatic solid cancer, or no cancer diagnosis. Methods Retrospective cohort study of all patients admitted to ICU in Australia or New Zealand between January 2000 and December 2022 with a primary admission diagnosis of sepsis and total white cell count <1.0 × 109 cells/L. Results We identified 8617 ICU admissions with neutropenic sepsis (hematological malignancy n = 4660; metastatic solid cancer n = 1034; no cancer n = 2800). Patients with hematological malignancy were younger (median, 61.5 years) with low rates of chronic comorbidities (4.7%) and were usually admitted to ICU from the ward (67.4%). Mechanical ventilation rates were 20.2% and in-hospital mortality was 30.6%. Patients with metastatic solid cancers were older (median, 66.3 years), with higher rates of chronic comorbidities (9.9%), and were usually admitted to the ICU from the emergency department (50.8%). Mechanical ventilation rates were 16.9% and in-hospital mortality was 42.4%. Patients with no documented cancer had highest rates of mechanical ventilation (41.7%) and mortality (46.3%). Neutropenia was independently associated with mortality among patients with solid cancers or no cancer but did not confer increased risk among patients with hematological malignancy (odds ratio, 0.98; 95% confidence interval,.90–1.06; P =.60). Conclusions Patients with neutropenic sepsis and hematological malignancy, metastatic solid cancer, or no cancer diagnosis constitute 3 distinct clinical groups. Management approaches should be tailored accordingly. [ABSTRACT FROM AUTHOR]

Marginal zone lymphomas (MZLs) are a rare, indolent group of non‐Hodgkin lymphomas with different diagnostic, genetic and clinical features and therapeutic implications. The most common is extranodal MZL of mucosa‐associated lymphoid tissue, followed by splenic MZL and nodal MZL. Patients with MZL generally have good outcomes with long survival rates but frequently have a relapsing/remitting course requiring several lines of therapy. The heterogeneous presentation and relapsing course present the clinician with several diagnostic and therapeutic challenges. This position statement presents evidence‐based recommendations in the setting of Australia and New Zealand. [ABSTRACT FROM AUTHOR]

Aim: Thrombocytopenia and bleeding are common in myelodysplastic syndromes (MDS), but optimal management is unknown. We conducted a survey to identify current clinical practice regarding platelet transfusion (PLT‐T) and tranexamic acid (TXA) to inform future trial design. Method: A 25‐question survey was distributed to members of the ALLG from December 2020 to July 2021. Results: Sixty‐four clinicians across Australia, New Zealand and Singapore responded. Clinicians treated a median of 15 MDS patients annually. Twenty‐nine (45%) reported having institutional guidelines regarding prophylactic PLT‐T. Although 60 (94%) said they would consider using TXA, most (58/64; 91%) did not have institutional guidelines. Clinical scenarios showed prophylactic PLT‐T was more likely administered for patients on disease‐modifying therapy (49/64; 76%, commonest threshold <10 × 109/L) or with minor bleeding (32/64 [50%] transfusing at threshold <20 × 109/L, 23/64 [35%] at <10 × 109/L). For stable untreated patients, 29/64 (45%) would not give PLT‐T and 32/64 (50%) would. Most respondents (46/64; 72%) were interested in participating in trials in this area. Potential barriers included resource limitations, funding and patient/clinician acceptance. Conclusion: Real‐world management of MDS‐related thrombocytopenia varies and there is a need for clinical trials to inform practice. [ABSTRACT FROM AUTHOR]

In the unique landscape of immunology research in New Zealand, this article explores the collaborative networks spanning the two main islands, through a conversation with Associate Professor Joanna Kirman and Dr Robert Weinkove. The discussions delve into their dynamic collaborations with countries such as Asia, Australia and the United States, from their laboratories at the University of Otago and the Malaghan Institute of Medical Research, respectively, provides insight into the translational research landscape of New Zealand, and the integration of Māori culture into all aspects of scientific research and clinical practise. Kirman's work in understanding immunological memory in tuberculosis and Weinkove's research in cancer immunotherapies, particularly CAR‐T cells, are highlighted. The natural beauty and accessibility of New Zealand supports its research diversity. [ABSTRACT FROM AUTHOR]

Despite widespread vaccination rates, we are living with high transmission rates of SARS‐CoV‐2. Although overall hospitalisation rates are falling, the risk of serious infection remains high for patients who are immunocompromised because of haematological malignancies. In light of the ongoing pandemic and the development of multiple agents for treatment, representatives from the Haematology Society of Australia and New Zealand and infectious diseases specialists have collaborated on this consensus position statement regarding COVID‐19 management in patients with haematological disorders. It is our recommendation that both patients with haematological malignancies and treating specialists be educated regarding the preventive and treatment options available and that patients continue to receive adequate vaccinations, keeping in mind the suboptimal vaccine responses that occur in haematology patients, in particular, those with B‐cell malignancies and on B‐cell‐targeting or depleting therapy. Patients with haematological malignancies should receive treatment for COVID‐19 in accordance with the severity of their symptoms, but even mild infections should prompt early treatment with antiviral agents. The issue of de‐isolation following COVID‐19 infection and optimal time to treatment for haematological malignancies is discussed but remains an area with evolving data. This position statement is to be used in conjunction with advice from infectious disease, respiratory and intensive care specialists, and current guidelines from the National COVID‐19 Clinical Evidence Taskforce and the New Zealand Ministry of Health and Cancer Agency Te Aho o Te Kahu COVID‐19 Guidelines. [ABSTRACT FROM AUTHOR]

Abstract Background Anti-CD19 chimeric antigen receptor (CAR) T cells have shown promise in the treatment of B cell acute lymphocytic leukemia (B-ALL). However, its efficacy in B-ALL patients with extramedullary involvement is limited due to poor responses and neurotoxicity. Here, we utilized a third generation of CAR T cell vector, which contains the Toll/interleukin-1 receptor (ITR) domain of Toll-like receptor 2 (TLR2), to generate 1928zT2 T cells targeting CD19, and evaluated the efficacy of 1928zT2 T cells in relapse or refractory B-ALL patients with extramedullary involvement. Methods 1928zT2 T cells were generated by 19-28z-TLR2 lentiviral vector transfection into primary human T lymphocytes. The anti-leukemia effect of 1928zT2 T cells were determined by killing assays and in xenografts. Three patients diagnosed as relapse or refractory ALL with extramedullary involvement were infused with 1928zT2 T cells, and the clinical responses were evaluated by BM smear, B-ultrasonography, PET/CT, histology, flow cytometry, qPCR, ELISA, and luminex assay. Results 1928zT2 T cells exhibited enhanced effector function against CD19+ leukemic cells in vitro and in a xenograft model of human extramedullary leukemia. Notably, the 1928zT2 T cells eradicated extramedullary leukemia and induced complete remission in the three relapse and refractory ALL patients without serious adverse effects. 1928zT2 T cells expanded robustly in the circulation of these three patients and were detected in the cerebrospinal fluid of patient 3. These three patients experienced cytokine release syndrome (CRS) with grade 2 or 3, which remitted spontaneously or after tocilizumab treatment. None of the three patients suffered neurotoxicity or needed further intensive care. Conclusions Our results demonstrate that 1928zT2 T cells with TLR2 incorporation augment anti-leukemic effects, particularly for eradicating extramedullary leukemia cells, and suggest that the infusion of 1928zT2 T cells is an encouraging treatment for relapsed/refractory ALL patients with extramedullary involvement. Trial registration ClinicalTrials.gov identifier NCT02822326. Date of registration: July 4, 2016.

Ibrutinib is a small molecule inhibitor of Bruton's tyrosine kinase indicated for the treatment of relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL). The Named Patient Program in Australia and New Zealand (ANZ NPP) provided access to ibrutinib treatment to 1126 R/R CLL/SLL and 330 R/R MCL patients, prior to Pharmaceutical Benefits Scheme listing. This study aimed to assess the duration of treatment for the ANZ NPP patients, as an indicator of efficacy and tolerability of ibrutinib in the real world. Based on the NPP data, ibrutinib provided a median of 47 months clinical benefit for participants with CLL/SLL and 14 months clinical benefit for those with MCL; outcomes that are consistent with the clinical trial results and further support the well-established efficacy and safety profile of ibrutinib in the real world. [ABSTRACT FROM AUTHOR]