IELSG38: phase II trial of front-line chlorambucil plus subcutaneous rituximab induction and maintenance in mucosa-associated lymphoid tissue lymphoma.

The IELSG38 trial was conducted to investigate the effects of subcutaneous (SC) rituximab on the complete remission (CR) rate and the benefits of SC maintenance in patients with extranodal marginal zone lymphoma (MZL) who received frontline treatment with chlorambucil plus rituximab. Study treatment comprised an induction phase with chlorambucil 6 mg/m2/day orally on weeks 1-6, 9-10, 13-14, 17-18, and 21-22, and rituximab 375 mg/m2 intravenously on day 1 of weeks 1-4, and 1400 mg SC on weeks 9, 13, 17, and 21. Then, a maintenance phase followed with rituximab administered at 1400 mg SC every two months for two years. Of the 112 patients enrolled, 109 were evaluated for efficacy. The CR rates increased from 52% at the end of the induction phase to 70% upon completion of the maintenance phase. With a median follow-up of 5.8 years, the 5-year event-free, progression-free, and overall survival rates were 87% (95% CI, 78-92), 84% (95% CI, 75-89), and 93% (95% CI, 86-96), respectively. The most common grade ≥3 toxicities were neutropenia (33%) and lymphocytopenia (16%). Six patients experienced treatment-related serious adverse events, including fever of unknown origin, sepsis, pneumonia, respiratory failure, severe cerebellar ataxia, and fatal acute myeloid leukemia. The trial showed that subcutaneous rituximab did not improve the complete remission rate at the conclusion of the induction phase, which was the main endpoint. Nevertheless, SC maintenance might have facilitated long-term disease control, potentially contributing to enhanced event-free and progression-free survival.

The educational contribution of the college of the European school of oncology (ESCO): A survey analysis of the first three years.

In July 2020, the European School of Oncology (ESO) launched ESCO www.esco.org - the College of the European School of Oncology. ESCO provides young oncologists with a structured educational pathway and access to dedicated career development benefits. The College is organized into three progressive levels which members reach by earning credits that are awarded to them as they follow the pathway and actively improve their oncology careers. In this article, we present and evaluate the success of ESCO and highlight how its stimulating structure and personalized career development opportunities satisfy and encourage oncologists (medical, surgical and radiation) to continue to develop and improve their knowledge and skills.

Changing the landscape of European School of Oncology-European Society for Medical Oncology masterclasses in clinical oncology during the COVID-19 pandemic.

Aims: This study aimed to assess the participants' evaluation of the European School of Oncology-European Society for Medical Oncology virtual masterclasses in clinical oncology (MCOs) organized during the pandemic in 2021. Materials & methods: The participants answered an online evaluation questionnaire at the end of each MCO to evaluate the content and organization of the MCO. Results: The clinical session and case presentation scores ranged between 4.6 and 4.8 over 5. The participants strongly agreed that the MCOs offered updates to improve their knowledge and practice in 68-83% and 52-76%, respectively; 74-90% of the participants considered the quality of the meetings to be excellent. Conclusion: The participants were satisfied with the virtual MCOs during the COVID-19 pandemic. Virtual MCO may be an acceptable alternative educational modality in specific circumstances.

In 2002, the European School of Oncology (ESO) established masterclasses in clinical oncology (MCOs) and provided 41 in-person courses over the past two decades. As the COVID-19 pandemic forced travel restrictions and social distancing, the ESO and the European Society for Medical Oncology (ESMO) adapted the traditional MCOs to create virtual MCOs presented on e-ESO, an ESO e-learning platform. To date, five virtual MCOs have been organized for oncologists from western Europe, Latin America, Arab countries and southern Europe, the Baltic and Eurasia, eastern Europe and the Balkans. This study aimed to assess the participants' evaluation of the ESO-ESMO virtual MCOs organized during the pandemic in 2021 and to compare the participants' evaluation with that of previous in-person MCOs conducted between 2002 and 2019.

Long-term efficacy, safety and neurotolerability of MATRix regimen followed by autologous transplant in primary CNS lymphoma: 7-year results of the IELSG32 randomized trial.

219 HIV-negative adults ≤70 years with primary CNS lymphoma (PCNSL) were enrolled in the randomized IELSG32 trial. Enrolled patients were randomly assigned to receive methotrexate-cytarabine (arm A), or methotrexate-cytarabine-rituximab (B), or methotrexate-cytarabine-thiotepa-rituximab (MATRix; arm C). A second randomization allocated patients with responsive/stable disease to whole-brain irradiation (WBRT) or carmustine-thiotepa-conditioned autologous transplantation (ASCT). First results, after a median follow-up of 30 months, showed that MATRix significantly improves outcome, with both WBRT and ASCT being similarly effective. However, sound assessment of overall survival (OS), efficacy of salvage therapy, late complications, secondary tumors, and cognitive impairment requires longer follow-up. Herein, we report the results of this trial at a median follow-up of 88 months. As main findings, MATRix was associated with excellent long-lasting outcome, with a 7-year OS of 21%, 37%, and 56% respectively for arms A, B, and C. Notably, patients treated with MATRix and consolidation had a 7-year OS of 70%. The superiority of arm B on arm A suggests a benefit from the addition of rituximab. Comparable efficacy of WBRT and ASCT was confirmed. Salvage therapy was ineffective; benefit was recorded only in patients with late relapse re-treated with methotrexate. Eight (4%) patients developed a second cancer. Importantly, MATRix and ASCT did not result in higher non-relapse mortality or second tumors incidence. Patients who received WBRT experienced impairment in attentiveness and executive functions, whereas patients undergoing ASCT experienced improvement in these functions as well as in memory and quality of life.

Reaching beyond maximum grade: progress and future directions for modernising the assessment and reporting of adverse events in haematological malignancies.

Remarkable improvements in outcomes for many haematological malignancies have been driven primarily by a proliferation of novel therapeutics over the past two decades. Targeted agents, immune and cellular therapies, and combination regimens have adverse event profiles distinct from conventional finite cytotoxic chemotherapies. In 2018, a Commission comprising patient advocates, clinicians, clinical investigators, regulators, biostatisticians, and pharmacists representing a broad range of academic and clinical cancer expertise examined issues of adverse event evaluation in the context of both newer and existing therapies for haematological cancers. The Commission proposed immediate actions and long-term solutions in the current processes in adverse event assessment, patient-reported outcomes in haematological malignancies, toxicities in cellular therapies, long-term toxicity and survivorship in haematological malignancies, issues in regulatory approval from an international perspective, and toxicity reporting in haematological malignancies and the real-world setting. In this follow-up report, the Commission describes progress that has been made in these areas since the initial report.

ESO's career development program (2002-2021): Presentation and evaluation.

Over the last two decades, the European School of Oncology (ESO) provided a career development program to young oncologists by offering extensive learning programs. In 2020, the College of ESO was established to provide a fully comprehensive educational pathway that covers the different needs of medical students, oncology fellows and specialists. The following educational activities were organized worldwide: i) the masterclass in clinical oncology, ii) fellowships in clinical training centers, iii) the certificate of competence and advanced studies, iv) the medical student courses in oncology, v) the live e-sessions, vi) the refresher courses and vii) the Visiting Professor Program; and have reached areas where education is most needed and offered a variety of educational events in Europe, Eurasia, Middle East and Latin America. In this article, we present and evaluate the ESO educational programs devoted to young oncologists over the last 20 years.

Eight-Year Experience of the Certificate of Competence and Advanced Studies Program Organized by the European School of Oncology.

The Certificate of Competence and Advanced Studies Program is an academically recognized postgraduate program that is organized by the European School of Oncology in collaboration with the University of Ulm and the University of Zurich. It is a part-time educational activity that aims to provide physicians and scientists with advanced knowledge in the management of patients with breast cancer, lymphoma, and lung cancer. The program encloses three attendance seminars and four to five e-learning modules that extend over 12 to 14 months. To be certified, participants have to pass an online test after each module followed by a final certification exam at the end of the program. This article reports on the 8-year experience of the 166 graduated fellows who have attended the program.

A phase I trial of inotuzumab ozogamicin in combination with temsirolimus in patients with relapsed or refractory CD22-positive B-cell non-Hodgkin lymphomas.

This phase I trial evaluated the safety, tolerability, and preliminary activity of inotuzumab ozogamicin in combination with temsirolimus in patients with relapsed/refractory CD22 positive B-cell non-Hodgkin lymphomas. Nineteen patients received at least one dose of both study drugs. Dose-limiting toxicities consisted of thrombocytopenia, hypertriglyceridemia, oral mucositis, clinical deterioration, and the inability to receive at least three doses of temsirolimus during cycle 1. The most common grade ≥3 treatment-related adverse events were thrombocytopenia (n = 8), neutropenia (n = 5), and two patients each hyperphosphatemia, lymphopenia, and hypertriglyceridemia. The recommended phase II dose was inotuzumab ozogamicin 0.8 mg/m2 on day 1 in combination with temsirolimus 10 mg on days 8, 15, and 22 every 28 days. Among 18 patients evaluable, seven (39%) with follicular lymphoma had a partial remission. This drug combination is not possible within a therapeutically useful range of doses due to toxicities. Antitumor activity was observed in heavily pretreated patients (ClinicalTrials.gov, Identifier NCT01535989).

The Contribution of the European School Of Oncology Education to the Central Asian and Caucasian Regions.

The European School of Oncology (ESO) organizes educational activities within Europe, the Mediterranean region, Central Asia, and the Caucasus. In this paper, we report on the participation of oncologists from Uzbekistan, Kazakhstan, Kirgizstan, Tajikistan, Azerbaijan, Georgia, and Armenia in various ESO activities including the masterclass, courses, refresher courses, conventions, conferences, consensus conferences, clinical training centers fellowship program, and the medical students' courses in oncology. Over the last 15 years, 428 oncologists and medical students have successfully attended one or more of the above activities organized in various European countries. This article details the implementation and coordination of the ESO educational events in the Central Asian and the Caucasian regions.

Understanding Immune Thrombocytopenia: Looking Out of the Box.

The pathogenesis of immune thrombocytopenia (ITP) is increasingly being elucidated, and its etiology is becoming more frequently identified, leading to a diagnostic shift from primary to secondary ITP. The overlap between autoimmunity, immunodeficiency, and cancer is evident, implying more interdisciplinarity in daily care. This mini-review is based on an expert meeting on ITP organized by the Intercontinental Cooperative ITP Study Group and presents the challenges of hematologists in understanding and investigating "out of the box" concepts associated with ITP.

Educational contribution of the College of the European School of Oncology to the Latin American Oncologists.

The European School of Oncology (ESO) offers a wide range of educational activities in Europe, the Middle East and Latin America. International experts are invited to provide proper education in the diagnosis and treatment of patients with cancer according to a holistic model of care. This activity is currently structured in the ESO College (ESCO) through masterclasses in clinical oncology, international conferences, clinical training centers fellowship programs, certificate of competence and advanced studies, patients' advocacy events, e-learning sessions and medical students' courses in oncology. This institutional profile highlights the ESO-ESCO educational activities dedicated to Latin American oncologists and reports on the experience of the 869 participants that have attended these programs.

Live European School of Oncology e-Sessions (e-ESO).

The European School of Oncology (ESO) embarked on an online educational project, starting with live sessions in 2008 (e-ESO). Our scholars and young oncologists identified the need to be offered independent high-level online education with contributions from experts around the world, free of charge and available at any moment. We report on various types of e-sessions, such as grand-rounds, highlights, debates, clinical cases and other sessions. Our audience has grown over the last decade, reaching 11,123 users who have viewed a total of 77,041 sessions since the beginning of 2008. Moreover, our activities on social media platforms have enhanced our visibility, reaching more physicians around the globe. Due to the recent events surrounding the COVID-19 pandemic, online education has proven to be of great value in offering long-distance teaching. We have analyzed the growth of our audience and its attendance over the last 12 years.

ESO-ESMO Masterclass in Clinical Oncology: Analysis and Evaluation of the Learning Self-Assessment Test.

Masterclass in Clinical Oncology (MCO) represents the "key educational event" of European School of Oncology's (ESO) teaching program. MCO in collaboration with European Society for Medical Oncology (ESMO) is a multidisciplinary and clinical oriented educational event offered mainly to young oncologists worldwide. It provides full immersion in oncology with clinical case presentations and a Learning Self-Assessment Test (LSAT).LSAT is consisting of 45 multiple choice questions on an electronic platform referring to the material taught during the MCO. Three questions related to their topics are requested in advance from each faculty member. The major intentions of LSAT are the following: (a) the learning reflection of the massive information given during 4-5 days of intensive teaching and (b) to offer the opportunity to the participants to prepare themselves for their National Boards or for ESMO examination.In this article, we are analyzing and evaluating the results of LSAT from the ESO-ESMO Central European MCOs. We used the information of Central European MCOs for analysis due to the homogeneity of the available data. We assessed the level of participants' knowledge in relation to their oncology specialty or to their country of origin and the level of the quality of faculty teaching.

Clinical Case Presentation and Discussion During ESO-ESMO Masterclass: a 10-Year Interactive Educational Experience.

In this article, we report on the clinical case presentations that have been delivered during the ESO or ESO-ESMO Masterclasses in Clinical Oncology in the last 10 years. Masterclasses have been held in three different geographical continents including Europe, Middle East, and Latin America, in which participants had to submit a clinical case and present it either in front of a tumor board (multidisciplinary-like sessions) or in small groups. Clinical case presentation is a unique part of the educational program preparing young oncologists to present and discuss their own patients with distinguished experts. In each Masterclass, between 40 and 55 clinical cases-depending on the number of participants-are presented. All presentations are assessed and evaluated by faculty members as well as by the rest of the participants.

A phase II trial of bendamustine in combination with ofatumumab in patients with relapsed or refractory marginal zone B-cell lymphomas.

Marginal zone lymphomas (MZLs) are indolent yet incurable lymphomas with frequent relapses following therapy. For patients with relapsed/refractory disease, no standard therapies exist. Here we report results of an exploratory phase II study aimed at assessing the efficacy and safety of the alkylator agent bendamustine in combination with the second-generation anti-CD20 monoclonal antibody, ofatumumab, in patients with relapsed or refractory MZL. Patients with MZL and previously treated with at least one line of systemic therapy were eligible. Treatment consisted in bendamustine (90 mg/m2 on days 1 and 2) and ofatumumab (1000 mg on day 1) in 28-day cycles for up to six cycles. Sixteen patients were included in the trial. In one patient, the diagnosis was revised after two cycles of treatment and was excluded from the efficacy analysis. Among 15 patients with MZL, 14 were evaluable for response: the overall and complete response rates were 92.9% and 57.1%, respectively. The median duration of response was 30.4 months (95% confidence interval [CI], 15.5 -not estimable) and 2-years progression-free survival 77% (95% CI, 43%-92%). Fifteen patients (94%) experienced grade 3-4 adverse events. Toxicity was mostly hematological. Neutropenia grade ≥3 was recorded in 27% of patients, lymphocytopenia in 93%, and infections and febrile neutropenia each in 13%. One patient discontinued treatment due to myocardial infarction; no treatment-related deaths occurred. The combination of bendamustine with ofatumumab was active with an acceptable toxicity profile in this small phase II trial and can be considered for further investigation in relapsed/refractory MZL patients.

Early progression of disease predicts shorter survival in MALT lymphoma patients receiving systemic treatment.

Early progression of disease (POD) within two years from diagnosis is linked with poor overall survival (OS) in follicular lymphoma but its prognostic role is less clear in extranodal marginal zone B-cell lymphoma (EMZL). We sought to identify prognostic factors associated with early POD and to determine whether is associated with inferior OS. We analyzed the impact of early POD in the IELSG19 clinical trial dataset (training set of 401 patients randomly assigned to chlorambucil or rituximab or chlorambucil plus rituximab). Reproducibility was examined in a validation set of 287 patients who received systemic treatment. In both sets, we excluded from the analysis the patients who, within 24 months from treatment start, died without progression or were lost to follow-up without prior progression. OS was calculated from progression in patients with early POD and from 24 months after start of treatment in those without (reference group). Early POD was observed in 69 of the 384 (18%) evaluable patients of the IELSG19 study. Patients with high-risk MALT-IPI were more likely to have early POD (p=0.006). The 10-year OS rate was 64% in the early POD group and 85% in the reference group (HR= 2.42, 95%CI, 1.35-4.34; log-rank P=0.002). This prognostic impact was confirmed in the validation set, in which early POD was observed in 64 out of 224 (29%) evaluable patients with 10-year OS rate of 48% in the early POD group and 71% in the reference group (HR= 2.15, 95%CI, 1.19-3.90; log-rank P=0.009). In patients with EMZL who received front-line systemic treatment, early POD is associated with poorer survival and may represent a useful endpoint in future prospective clinical trials.