Preface – EHA 2022 Matthew S. Davids, MD, MMSc – Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA Dear Colleagues, After 2 years of the COVID-19 pandemic, the Annual Meeting of the American Society of Clinical Oncology, held in Chicago, USA, and virtually from 3rd–7th June 2022, featured nearly 250 oral as well as over 2,200 poster presentations.

Updates and ancillary analyses in the setting of chronic lymphocytic leukemia Progression-free survival in GAIA/CLL13 In fit patients with advanced CLL of favorable genetic risk, chemoimmunotherapy (CIT) consisting of fludarabine/cyclophosphamide/rituximab (FCR) or bendamustine/rituximab (BR) still represents the treatment standard. Another potential strategy, however, is time-limited therapy consisting of obinutuzumab plus venetoclax (GV) with or without a BTK inhibitor. The four-arm, randomized, phase III GAIA/CLL13 trial compared GV and GV plus ibrutinib (GIV) to 6 cycles of FCR (patient age ≤ 65 years) or BR (> 65 years) in fit patients (i.e., CIRS scores ≤ 6 and normal creatinine clearance) in whom TP53 mutation and deletion 17p had been excluded. In the fourth study arm, rituximab plus venetoclax (RV) was administered. Overall, the trial contained 926 patients. The regimens were administered for a maximum of 12 cycles; only ibrutinib was allowed to be continued for up to 3

Marginal zone lymphoma: benefits of BTK inhibition in later lines Zanubrutinib in patients ≥ 65 years Patients with marginal zone lymphoma (MZL) usually show an indolent course of disease, although MZL remains largely incurable, particularly in the relapsed/refractory setting [1, 2].

Early-phase trials investigating novel agents in miscellaneous B-cell malignancies Large B-cell lymphoma: subcutaneous epcoritamab The prognosis is still poor for most patients with relapsed or refractory large B-cell lymphoma (LBCL) irrespective of therapeutic advances that have recently been achieved.

BTK inhibition in Waldenström’s macroglobulinemia: trial updates and real-world insights The open-label, multicenter, ran­domized phase III ASPEN trial was set up to assess the efficacy and safety of the potent, selective, irreversible next-generation BTK inhibitor zanubrutinib in Waldenström’s macroglobulinemia (WM).

Prolonging remission in relapsed and refractory follicular lymphoma Follicular lymphoma (FL) is a common indolent form of non-Hodgkin lymphoma that accounts for 20-25 % of all new NHL cases in Western countries [1].

New options in untreated and pretreated mantle cell lymphoma SHINE trial: first-line regimen for older patients Patients of an advanced age with previously untreated mantle cell lymphoma (MCL) usually receive chemoimmunotherapy regimens such as bendamustine/rituximab (BR), R-CHOP or bortezomib/rituximab/cyclophosphamide/doxorubicin/prednisone (VR-CAP), with BR having become the most commonly used first-line strategy [1].

Tackling acute myeloid leukemia via diverse pathways Mutations of FLT3 are found in approximately 30 % of patients with newly diagnosed acute myeloid leukemia (AML), with the internal tandem duplication (ITD) representing the most common type [1-4].

Preface – ASCO/EHA/ICML 2021 Véronique Leblond, MD Department of Hematology, Pitié Salpêtrière Hospital Paris, France Dear Colleagues, As virtual scientific conferences are becoming part of our daily routine as clinicians and researchers, information in individual areas of interest is easily accessible across different congresses.

CLL/SLL: current perspectives across a range of potent agents ALPINE: zanubrutinib vs. ibrutinib The introduction of effective inhibitors of B-cell receptor signaling such as the BTK inhibitor ibrutinib has transformed the treatment of patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

Waldenström’s macroglobulinemia: outcome optimization via combinations Final analysis of iNNOVATE Ibrutinib is the only once-daily BTK inhibitor approved as a single agent or in combination with rituximab for patients with Waldenström’s macroglobulinemia (WM) across all lines of therapy.

Successful inhibition of PI3K, BTK, BCL2 and other targets in various B-cell malignancies CHRONOS-3: copanlisib plus rituximab Rituximab monotherapy is a recognized standard of care in patients with relapsed indolent non-Hodgkin lymphoma (iNHL) who have had long remissions after rituximab-based therapy or who are unwilling or unfit to be treated with chemotherapy.

Extending anti-PD-1–based options in the setting of Hodgkin lymphoma Patients with relapsed or refractory classical Hodgkin lymphoma (cHL) who have failed high-dose chemotherapy and autologous stem cell transplantation (HDT/ASCT) have poor prognosis, which also applies to those with chemotherapy-resistant disease who are ineligible for HDT/ASCT [1-4].

Mantle cell lymphoma: improving outcomes in difficult-to-treat patient populations Updated results from MAGNIFY Mantle cell lymphoma (MCL) accounts for approximately 3–10 % of non-Hodgkin lymphomas and shows one of the poorest survival rates among the lymphomas [1, 2].

Zanubrutinib in relapsed/refractory marginal zone lymphoma: MAGNOLIA B-cell receptor-mediated signaling has been identified as a critical step in marginal zone lymphoma (MZL) pathogenesis [1].

Novel bispecific antibodies in CD20-positive B-cell non-Hodgkin lymphomas Glofitamab step-up dosing The T-cell–engaging bispecific antibody glofitamab has been designed with a 2:1 configuration that enables bivalent binding to CD20 on B cells and monovalent binding to CD3 on T cells [1]. Compared to alternative bispecific formats, this offers greater avidity, potency and combinability with other anti-CD20 IgG antibodies.

Preface – EHA 2020 Constantine Tam, MB, BS (Hons), MD, FRACP, FRCPA, Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne Melbourne, Australia Dear Colleagues, Due to the circumstances brought about by the COVID-19 pandemic, the 25th European Hematology Association (EHA) Annual Congress had to take place as a virtual edition, although this raised new possibilities such as a 10-day program.

Waldenström’s macroglobulinemia: BTK inhibition and other treatments Within the group of non-Hodgkin lymphoma, Waldenström’s macroglobulinemia (WM), an indolent B-cell lymphoplasmacytic lymphoma, accounts for approximately 2 % of cases [1]. This disease is deemed incurable and typically involves infiltration of tissues such as bone marrow, lymph nodes and/or spleen with clonal lymphoplasmacytic cells, as well as serum monoclonal paraprotein production.

Optimizing timing, efficacy and tolerability in chronic lymphocytic leukemia Acalabrutinib vs. ibrutinib In both treatment-naïve and relapsed/refractory patients with chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL), inhibition of Bruton’s tyrosine kinase (BTK) represents a treatment standard as it has improved clinical outcomes [1]. Compared to the first-generation agent ibrutinib, the second-generation, highly selective BTK inhibitor acalabrutinib shows minimal off-target kinase inhibition [2], thus potentially offering an optimized safety profile.

Changing paradigms in the management of mantle cell lymphoma Mantle cell lymphoma (MCL) is a rare, heterogenous and generally aggressive subtype of B-cell non-Hodgkin lymphoma that remains incurable in the majority of cases. Median survival in non-trial patients has been estimated at 3 to 5 years [1]. First-line therapy usually consists of chemoimmunotherapy, while both immunochemotherapy and targeted agents are recommended in relapsed disease [2]. However, trials increasingly challenge the role of chemotherapy against the novel agents, especially in the front-line setting.

Targeted approaches in various B-cell malignancies Zanubrutinib plus rituximab BTK inhibitors are active in many B-cell malignancies such as mantle cell lymphoma, CLL and Waldenström’s macro­globulinemia, but also in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and marginal zone lymphoma (MZL). Zanubrutinib is currently being assessed in pivotal phase II and III studies in all of these indications. An ongoing, single-arm, multicenter, phase II study is evaluating zanubrutinib plus rituximab in patients with relapsed/refractory non-germinal center B-cell-like (non-GCB) DLBCL (n = 20), FL (n = 16) and MZL (n = 5).

Cold agglutinin disease: on the road to new insights and potential treatment options Cold agglutinin disease (CAD) is a rare type of autoimmune hemolytic anemia (AIHA) elicited by cold-sensitive antibodies including cold agglutinins. Ninety percent of cold agglutinins belong to the IgM kappa category and bind to red blood cell surface antigens at temperatures of ≤ 37 °C, thus inducing hemolysis [1-3]. CAD accounts for approximately 25 % of AIHA cases, with an incidence and prevalence of 1 case per million persons per year and 16 cases per million persons, respectively [4, 5].

Patient and disease characteristics in a small CAD cohort A retrospective analysis hints at the wide range of cold agglutinin disease (CAD) clinical behavior. Koudouna et al. investigated the characteristics of 8 patients with CAD at the time of diagnosis [1]. Median age was 62 years, and 5 patients were women. Hematologic malignancies constituted 50 % of underlying medical conditions; in 37 %, hepatitis B/C was the associated disease, and in 13 %, autoimmune disorders. The median hemoglobin level at presentation was 8.9 g/dL. Slightly elevated serum CRP and ferritin levels represented common findings.

Paroxysmal nocturnal hemoglobinuria: improving outcomes with novel strategies Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, potentially life-threatening clonal hematopoietic stem cell disorder characterized by hemolytic anemia, bone marrow failure, thrombosis, and peripheral blood cytopenia.