Preface – ASCO/EHA/ICML 2023

© Dirk Gillissen – Arnon P. Kater, MD, PhD, Department of Hematology, Cancer Center Amsterdam, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

© Dirk Gillissen – Arnon P. Kater, MD, PhD, Department of Hematology, Cancer Center Amsterdam, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands

Dear Colleagues,

Cutting-edge updates in the diagnosis and treatment of hematological malignancies were discussed by world-leading experts at the Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, USA, 2nd–6th June 2023, the European Hematology Association (EHA) congress in Frankfurt, Germany, 8th–11th June 2023, and the 17th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland, 13th–17th June 2023.

Over the last decade, the treatment of chronic lymphocytic leukemia has dramatically evolved due to the introduction of targeted therapies, but questions remain. In treatment-naïve asymptomatic disease, the watch & wait concept was challenged but appears to be superior to early BTK inhibitor treatment. Chemotherapy-free fixed-duration regimens have shown clinically meaningful benefits and deep, durable responses and are an attractive alternative to continuous treatment, avoiding long-term toxicity, high-costs and potentially inevitable development of ­resistant clones. At the same time, the results provide the rationale for the implementation of MRD-guided strategies to further improve patient prognosis. The next-generation BTK inhibitor zanubrutinib has become a new first-line treatment in the elderly, in patients with comorbidi­ties, and in those with adverse genetic setup. In relapsed/refractory CLL, the feasibility of venetoclax/rituximab retreatment in the context of fixed-duration strategies has been demonstrated. Also, data show that some BTK inhibitors offer advantages over others in the presence of intolerability and BTK mutations.

Bispecific antibodies are on the rise in hematological malignancies, which is highlighted in this report by findings obtained in the setting of follicular lymphoma and diffuse large B-cell lymphoma. Nevertheless, BTK inhibition remains a mainstay of treatment in hematological diseases such as marginal zone lymphoma and Waldenström macroglobulinemia. In elderly patients with diffuse large B-cell lymphoma, the antibody-drug conjugate polatuzumab vedotin has yielded encouraging efficacy combined with chemotherapy. Moreover, promising findings have been observed with novel agents targeting BTK and Bcl-2 in various B-cell malignancies.

Once again, experts shared groundbreaking results in the field of hematological oncology by presenting impressive long-term follow-up data as well as innovative treatment strategies at this year’s ASCO, EHA and ICML meeting. Leaving Chicago, Frankfurt and/or ­Lugano, we all feel excited and inspired to share our newly acquired knowledge not only with you, as a reader of this special issue, but also with our patients since science creates knowledge and saves lives.

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DLBCL: treatment of elderly patients and relapsed disease

Overall survival has improved considerably in the setting of diffuse large B-cell lymphoma (DLBCL). However, patients above the age of 80 years are an exception in terms of survival prolongation and therefore face an unmet clinical need [1]. At the same time, this is a group that constitutes an increasing proportion of DLBCL patients.

Waldenström macroglobulinemia: findings from ASPEN and BRUIN

In the management of patients with Waldenström macroglobulinemia (WM), BTK inhibitors have changed the therapeutic landscape and are considered preferred treatment options for the first and later lines. Compared to the first-in-class agent ibrutinib, the potent and irreversible BTK inhibitor zanubrutinib offers improved BTK selectivity that minimizes off-target effects and toxicities.

Outcome improvements in relapsed and untreated marginal zone lymphoma

Systemic treatment for patients with advanced marginal zone lymphoma (MZL) is often based on regimens used in follicular lymphoma, although new agents and combinations are called for. As MZL ­depends on B-cell receptor signaling, treatment with BTK inhibitors is being investigated in clinical trials.

Follicular lymphoma: study results with bispecific antibodies and BTK inhibitors

Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma (NHL) subtype [1]. In general, it remains incurable with standard therapies, and most patients experience multiple relapses over time. Therefore, there remains a great need for innovative new regimens such as the first-in-class CD20xCD3 T-cell–engaging bispecific antibody mosunetuzumab that is being tested in a pivotal phase II trial in patients with relapsed/refractory grade 1-3a FL after ≥ 2 lines of therapy (including an anti-CD20 antibody and an alkylating agent).

Current insights into BTK inhibition and other targeted approaches in CLL

In the setting of early-stage, asymptomatic chronic lymphocytic leukemia (CLL), the concept of watch & wait in the era of targeted agents was challenged by the placebo-controlled, double-blind, phase III CLL12 study. This trial assessed the use of ibrutinib 420 mg OD (n = 182) vs. placebo (n = 181) until symptomatic disease progression in treatment-naïve patients with asymptomatic CLL Binet stage A who had an increased risk due to factors such as del(17p), IGHV mutation status, or age.