Nachwuchsfƶrderung in der Onkologie: Kongress-Highlights der YOA-Teilnehmenden ā Teil 2
Das Swiss Cancer Institute lanciert 2026 bereits zum elften Mal die Young Oncology Academy (YOA), ein Fƶrderprogramm fĆ¼r den forschenden Nachwuchs. Es richtet sich an engagierte junge Ćrzte aus den Bereichen Onkologie, HƤmatologie, Radioonkologie, Urologie, GynƤkologie, Pathologie oder Dermatologie, die sich vertieft mit onkologischen und hƤmatologischen Fragestellungen auseinandersetzen mƶchten.
Das vielseitige einjƤhrige Curriculum umfasst unter anderem Kongressbesuche im In- und Ausland (ESMO, EHA, ESTRO, ESP etc.), PrƤsentations- und Schreibtrainings, Networking, Grant-Submission-Workshops, Einblicke in Phase-I-Studien sowie in die klinische und translationale Forschung und EinfĆ¼hrungen in statistische Grundlagen. Die Teilnehmer werden von erfahrenen onkologischen Fachpersonen als Mentoren begleitet und erhalten zudem die Mƶglichkeit, eigene Studienprojekte zu entwickeln und vorzustellen.
Zum Jahresende publizieren die YOA-Teilnehmer jeweils ein Paper zu ihren persƶnlichen Highlights eines internationalen Kongresses. Wir freuen uns, die Arbeiten aus dem Jahr 2025 in einer dreiteiligen Serie prƤsentieren zu dĆ¼rfen. Nachdem in der letzten Ausgabe der Auftakt dieser Reihe erschienen ist, folgt in der vorliegenden Ausgabe der zweite Teil mit weiteren BeitrƤgen der Mentees.
Wir beide haben diese YOA besucht und kƶnnen das Programm sehr empfehlen. Weitere Informationen finden sich auf der Website des Swiss Cancer Institute:
https://www.swisscancerinstitute.ch/de/forschende/young-oncology-academy/
Dr. med. TƤmer El SaadanyĀ Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Ā Dr. med. Eveline Daetwyler
My highlights on myeloproliferative neoplasms from the 2025 EHA Congress
Review YOA 2025: HƤfliger Emmanuel
Mentee: HƤfliger Emmanuel, UniversitƤtsklinik fĆ¼r HƤmatologie, Inselspital
Mentor: Prof. Dr. med. Gabriela Baerlocher, Klinik fĆ¼r HƤmatologie und Onkologie, Hirslanden ZĆ¼rich und Medica Medizinische Laboratorien und Pathologie, ZĆ¼rich
Speciality: Hematology
Year: Young Oncology Academy 2025
Abstract S166 EHA 2025 by Andreas Hochhaus et al. (1)
Chronic myeloid leukemia (CML) has entered a new era of treatment with the introduction of tyrosine kinase inhibitors (TKIs), which have led to a near-normalization of life expectancy for most patients (2). Despite their remarkable efficacy, currently available TKIs all target the ATP-binding site of BCR::ABL1 and are associated with off-target toxicity. Asciminib represents a novel agent that targets the myristoyl pocket of BCR::ABL1, providing a new mechanism of action and the potential for an improved safety profile (3). In the ASC4FIRST trial, investigators evaluated whether asciminib achieved superior 48-week major molecular response compared with investigator-selected standard TKIs in newly diagnosed chronic-phase CML and found that asciminib demonstrated comparable ā but not superior ā efficacy relative to second-generation TKIs. Although a statistically significant advantage in efficacy over second-generation TKIs was not shown, asciminib appeared to offer a more favorable safety profile ā an essential consideration in a chronic disease requiring lifelong therapy ā thereby paving the way for a dedicated tolerability-focused trial.
The phase IIIb ASC4START trial evaluated the safety and efficacy of asciminib versus nilotinib as first-line therapy in adults with newly diagnosed chronic-phase CML. Patients were randomized to receive either asciminib 80 mg once daily or nilotinib 300 mg twice daily. The primary endpoint of the study was the time to treatment discontinuation due to adverse events ā both hematologic and non-hematologic (including gastrointestinal, cardiovascular, and general symptoms such as fatigue) ā or death. Key secondary endpoints included type of adverse events and molecular response rates. This abstract presents data from an interim analysis conducted after 50 treatment discontinuations due to adverse events and/or death. At a median follow-up of 9.7 months, asciminib was associated with a significantly lower risk of treatment discontinuation due to adverse events compared with nilotinib (HR 0.45; 95ā% CI 0.25ā0.81; p = 0.004). Overall, asciminib seemed to demonstrate superior tolerability compared with nilotinib, leading the authors to advocate for its use as a frontline therapy for newly diagnosed chronic-phase CML. A limitation of this analysis is that asciminib was only compared to nilotinib, rather than to all second-generation tyrosine kinase inhibitors, limiting the generalizability of the findings. As the study primarily focused on tolerability, it does not yet demonstrate an improvement in overall survival, underscoring the need for further long-term investigations to establish the full clinical benefit of asciminib in the first-line setting.
Abstract LB4002 EHA 2025 by John ĀMascarenhas et al. (4)
Essential thrombocythemia (ET) is the second most common myeloproliferative neoplasm, yet its treatment remains largely non-specific and is currently limited to hydroxyurea, anagrelide, and off-label interferon (5). In recent years, JAK inhibitors have introduced the possibility of targeting driver pathways. Unfortunately, JAK inhibitors failed to demonstrate clinical efficacy in ET in the MAJIC-ET trial (6). These findings paved the way toward the search of novel therapeutic agents, including targeting alternative pathways.
In their work, J. Mascarenhas et al., evaluated INCA33989, a monoclonal antibody targeting mutant CALR. This first-in-human, open-label, dose-escalation study enrolled patients with high-risk CALR-mutated ET and therapy refractoriness and/or intolerance. 49 patients were included and received monoclonal antibody doses ranging from 24 mg up to 2,500 mg intravenously every two weeks. Median treatment exposure was 22.6 weeks. No dose-limiting toxicities were identified and serious treatment emergent adverse events were only reported in 6.1ā% of the patients (n=3). Those events were asymptomatic lipase increase (n=1), visceral venous thrombosis (n=1) and diverticulitis (n=1). Thrombocytopenia was not observed amongst the studied population. Higher haematologic response was observed in patients receiving higher doses of treatment (doses ranging from 400 mg to 2500 mg). A reduction in the variant allele frequency (VAF) of mutated CALR was observed in 89ā% of evaluable patients with 47ā% of patients reaching a VAF reduction of over 20ā% and 21ā% of the patients reaching a VAF reduction of over 50ā% . These early-phase data suggest a good tolerability and efficacy of this new monoclonal antibody against mutated CALR, introducing a novel mutation-targeted approach for patients with ET. Further data and longer follow-up will have to assess durability of responses, impact regarding thrombosis and cardiovascular risk, risk of transformation and overall survival.
Literatur
1. Andreas Hochhaus THB, Francois-Xavier Mahon, Delphine Rea, David J. Andorsky, Susanne Saussele, Stephen Strickland, Thomas Cluzeau, Francoise Huguet, JirĆ Mayer, Viviane Dubruille, DW Kim, Ilina Micheva, Gabrielle Roth Guepin, Virginia Pilipovic, Jacqueline Ryan, Aoife Smyth, Nabil Amirouchene Angelozzi, Ennan Gu, Himanshu Pokhriyal, Philipp Le Coutre. Asciminib (Asc) shows superior tolerability vs Nilotinib (Nil) in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): primary endpoint results of the phase (ph) 3b ASC4START Trial. EHA2025.
2. Bower H, Bjorkholm M, Dickman PW, Hoglund M, Lambert PC, Andersson TM. Life Expectancy of Patients With Chronic Myeloid Leukemia Approaches the Life Expectancy of the General Population. J Clin Oncol. Aug 20 2016;34(24):2851-7. doi:10.1200/JCO.2015.66.2866
3. Yeung DT, Shanmuganathan N, Hughes TP. Asciminib: a new therapeutic option in chronic-phase CML with treatment failure. Blood. Jun 16 2022;139(24):3474-3479. doi:10.1182/blood.2021014689
4. John Mascarenhas HA, Abdulraheem Yacoub, Tania Jain, Lynette Chee, Vikas Gupta, Claire Harrison, Jean-Jacques Kiladjian, Ruben Mesa, William Shomali, Makoto Yoshimitsu, Rosa MarĆa Ayala DĆaz, Aaron T. Gerds, Joan How, Steffen Koschmieder, Lucia Masarova, Caroline McNamara, Francesca Palandri, Francesco Passamonti, Andrew Perkins, Beth Psaila, Kazuki Sakatoku, Frank Stegelmann, Natasha Szuber, Alessandro Vannucchi, Hiroki Yamaguchi, Erin Crowgey, Betty Lamothe, Chenwei Tian, Tatiana Zinger, Evan Braunstein, David Ross. INCA33989 is a novel first in class, mutant calreticulin-specific monoclonal antibody that demonstrates safety and efficacy in patients with essential thrombocythemia (ET) EHA2025.
5. Tefferi A, Vannucchi AM, Barbui T. Essential thrombocythemia: 2024 update on diagnosis, risk stratification, and management. Am J Hematol. Apr 2024;99(4):697-718. doi:10.1002/ajh.27216
6. Harrison CN, Mead AJ, Panchal A, et al. Ruxolitinib vs best available therapy for ET intolerant or resistant to hydroxycarbamide. Blood. Oct 26 2017;130(17):1889-1897. doi:10.1182/blood-2017-05-785790
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Aerzteverlag medinfo AG
Filling the gap for Car T cell therapy
Review YOA 2025: Francesco Manfredi
Mentee: Dr. med. Dr. sc. nat. Francesco Manfredi, Klinik fĆ¼r medizinische Onkologie und HƤmatologie, USZ
Mentor: Prof. Dr. med. Gabriela Baerlocher, Klinik fĆ¼r HƤmatologie und Onkologie, Hirslanden ZĆ¼rich und Medica Medizinische Laboratorien und Pathologie, ZĆ¼rich
Speciality: Hematology ā Cellular Therapies
Year: Young Oncology Academy 2025
Chimeric antigen receptor (CAR) T-cell therapy for hematological malignancies continues to expand rapidly, both in terms of approved products and new clinical indications. However, as applications broaden, the field increasingly faces delays in production and limited accessibility due to the constraints of current manufacturing processes.
Most approved CAR T-cell therapies are autologous ā generated from a patientās own T lymphocytes. This approach presents several challenges. In heavily pretreated patients or those with a high circulating tumor burden, it can be difficult to obtain enough viable T cells to expand and meet manufacturing requirements. In addition, CAR T-cell production usually takes several weeks, exposing patients to the risk of disease progression before infusion. The process is also costly, labor-intensive, and centralized in a few specialized facilities, leading to long waiting times, logistical bottlenecks, and limited treatment availability as demand increases.
At the 2025 Annual Meeting of the European Hematology Association (EHA), part of the cell therapy session focused on these manufacturing challenges, with a focus on the need to treat high-risk patients (i.e. those heavily pretreated, with high tumor burdens, or rapidly progressing) and to make therapy accessible to more centers. Two presentations were particularly noteworthy in proposing innovative solutions to these problems.
The first, presented by Dr. Long and colleagues from Beijing (Abstract S283) (1, 2), reported the phase I/II clinical trial results on allogeneic universal anti-CD7 CAR T-cell for T-cell acute lymphoblastic leukemia (T-ALL). Unlike autologous products, a total of eight healthy donors provided all the batches for this Ā«off-the-shelfĀ» CAR T-cells. To prevent CAR T rejection, graft-versus-host disease (GvHD), and fratricide among CAR T-cells, the team used genome editing to eliminate surface expression of HLA molecules, the T-cell receptor, and CD7. This allogeneic approach dramatically shortened production timelines: the median time from screening to infusion was approximately three weeks, eliminating the need for bridging therapy. Because the therapy did not depend on harvesting viable T-cells from each patient, no manufacturing failures occurred, and even patients with high circulating blast counts could be treated successfully. Safety remains a key concern for allogeneic CAR T products, given potential risks of immune rejection and off-target effects. Dr. Longās team reported a safety profile comparable to approved autologous CAR T-cell therapies, including manageable rates of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and immune effector cell-associated hematotoxicity (ICAHT). Long-term safety assessment was limited, as all patients underwent consolidative allogeneic stem cell transplantation about 60 days postinfusion, but no unexpected toxicities were observed. The combined CAR T-cell plus transplant approach achieved complete remission (CR) in approximately 60ā% of patients with a median follow-up of two years. Importantly, efficacy was maintained in patients with extramedullary disease ā a subgroup typically associated with poor prognosis ā with a 57ā% CR rate at the full therapeutic dose. These encouraging results represent a major milestone for allogeneic CAR T-cell therapy, supporting its feasibility, safety, and potential scalability.
The second notable presentation (Abstract S281) (3), delivered by Dr. Mutsaers, focused on accelerating and decentralizing autologous CAR T-cell production. The team introduced a novel manufacturing platform capable of generating a CAR T-cell product within seven days of leukapheresis, significantly faster than the traditional multiweek process. This was achieved by shortening the culture period and decentralizing production, thereby eliminating the need for shipping of patient material to the production centre. The resulting CAR T-cells maintained an early T-cell memory phenotype, which may contribute to improved persistence and long-term disease control. Early clinical results showed a favorable safety profile, with low rates of severe CRS and ICANS, possibly reflecting the slower, more sustained cytotoxic activity of memory T-cells. Efficacy was evaluated in patients with both aggressive (DLBCL, MCL) and indolent (FL, MZL) B-cell non-Hodgkin lymphomas. At dose level 2, responses in DLBCL were comparable to those seen with approved CAR T-cell products, while outcomes in indolent lymphomas were particularly favourable. Whether these superior responses are due to enhanced CAR T-cell persistence remains under investigation, as longer-term follow-up is needed, especially in indolent lymphomas where relapses can occur months or years after treatment.
Together, these two studies exemplify the innovation currently shaping the CAR T-cell field. The allogeneic Ā«off-the-shelfĀ» approach offers a scalable solution to production bottlenecks, while accelerated, decentralized manufacturing could make autologous therapies faster and more widely accessible. The findings presented at EHA 2025 underscore the fieldās ongoing evolution toward making CAR T-cell therapy not only more efficient but also more clinically impactful. Continued research will determine how these advances translate into broader real-world adoption and improved patient outcomes.
Literatur
1. Xie L, Gu R, Yang X, Qiu S, Xu Y, Mou J, Wang Y, Xing H, Tang K, Tian Z, Rao Q, Wang M, Wang J. Universal Anti-CD7 CAR-T Cells Targeting T-ALL and Functional Analysis of CD7 Antigen on T/CAR-T Cells. Hum Gene Ther. 2023 Dec;34(23-24):1257-1272. doi: 10.1089/hum.2023.029. Epub 2023 Nov 24. PMID: 37861302.
2. Peihua Lu, Ying Wang, Jiang Cao, Keshu Zhou, Xiaoyu Zhu, Sanbin Wang, Kai Hu, Heng Mei, Yali Zhou, Jan K
Davidson-Moncada, Jiangtao Ren. (S283) CTD402: A UNIVERSAL ANTI-CD7 CHIMERIC ANTIGEN RE-CEPTOR T-CELL THERAPY FOR PATIENTS WITH RELAPSED OR REFRACTORY (R/R) T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA/LYMPHOBLASTIC LYMPHOMA (T-ALL/LBL). Plenary Abstracts Session & Oral Presentations. HemaSphere 2025, 9: e70151. https://doi.org/10.1002/hem3.70151
3. Joost Vermaat, SƩbastien Anguille, Maria Kuipers, Pim Mutsaers, Evelyne Willems, Michael Bishop, Tim Dekker, Martin Dreyling, Caron Jacobson, Sandra Blum, Omotayo Fasan, Harini Kothari, Eva Santermans, Jeevan Shetty, Kirsten Van Hoorde, Marie JosƩ Kersten. (S281) LOW RATES OF HIGH-GRADE TOXICI-TIES WITH GLPG5101, A FRESH, STEM-LIKE, EARLY MEMORY PHENOTYPE ANTI-CD19 CAR T-CELL THERAPY IN PATIENTS WITH NON-HODGKIN LYMPHOMA IN THE ATALANTA-1 STUDY. Plenary Ab-stracts Session & Oral Presentations. HemaSphere 2025, 9: e70151. https://doi.org/10.1002/hem3.70151
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Kantonsspital GraubĆ¼nden
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