Preface – iwCLL 2023

© author’s own – Kiyomi Mashima MD, PhD, Medical Oncology, CLL Center, Dana-Farber Cancer Institute, Boston, MA, USA, Department of Medicine, Harvard Medical School, Boston, MA, USA

Dear Colleagues,

The 20^th International Workshop on chronic lymphocytic leukemia (iwCLL) was held in Boston, USA, and virtually from 6^th–9^th October 2023. This conference featured 11 sessions committed to discussing the management of patients with CLL world-wide and to creating progress regarding patient outcomes.

In the treatment of CLL, targeted drugs are continuously gaining ground. Continuous use of Bruton tyrosine kinase inhibitors (BTKi) including ibrutinib, acalabrutinib, and zanubrutinib has significantly improved treatment standards. While these drugs are highly effective, especially in high-risk CLL, they usually do not eliminate leukemia entirely.

Thus, in the first chapter of this memo inHaematology special issue, the pros and cons of various first-line treatment options are outlined. Differences in toxicity profiles among BTK inhibitors allow for the tailoring of treatment and switching in case of intolerance. Recent studies have also been investigating the combination of BTK and BCL-2 inhibitors; this approach offers potential benefits regarding the emergence of resistance and tolerability. Additionally, the merits of time-limited doublet and triplet therapies in CLL are elaborated. Promising results from studies have been obtained on combinations involving ibrutinib, acalabrutinib or zanubrutinib with venetoclax and obinutuzumab, with second-generation BTK inhibitors giving rise to numerically higher uMRD rates compared to ibrutinib.

In chapter 2, long-term follow-up data on fixed-duration venetoclax plus rituximab (MURANO trial) and obinutuzumab plus acalabrutinib and venetoclax (CLL2-BAAG trial) in the relapsed/refractory setting are summarized, as well as study results on zanubrutinib plus obinutuzumab and venetoclax in previously untreated CLL patients (BOVen trial) and first-line zanubrutinib monotherapy in CLL patients unsuitable for chemoimmunotherapy (SEQUOIA trial). Health-related quality-of-life data from the ALPINE study and pooled safety data on zanubrutinib vs. ibrutinib are discussed.

Furthermore, this report delves into the complex world of resistance mechanisms to targeted inhibitors in the treatment of CLL, shedding light on subclonal mutations, primary resistance, and the role of critical signaling pathways. The emerging strategies of non-covalent BTK inhibition, BTK degradation, and alternative treatments like zanubrutinib for patients intolerant to other BTK inhibitors are outlined, providing valuable insights for clinicians and researchers.

Next, this report focuses on real-world CLL treatment insights from around the globe, such as evolving treatment trends in the USA, the efficacy of BTK inhibitors in China and the impact of hypertension on patient outcomes in Denmark.

Last but not least, survey findings identifying gaps regarding unmet needs between low-/middle-income countries and high-income countries are discussed. As a remarkable example, the achievements of the iwCLL capacity-building program in Tanzania are highlighted.

The iwCLL 2023 once again provided an outstanding platform to display the dynamic advancements in global CLL care. In accordance with the iwCLL vision of a world where every CLL patient can be cured, I hope you enjoy reading this special issue!

© 2023 Springer-Verlag GmbH, Impressum

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