The 29th Annual Meeting of the European Hematology Association (EHA) was grandly held from June 13-16, 2024, in Madrid, Spain. As the largest international conference in the field of hematology in Europe, it attracts experts and scholars from around the world each year to share and discuss innovative concepts and the latest scientific and clinical research results in hematology. At this year's conference, Professor Xiaohui Zhang's team from Peking University People's Hospital performed outstandingly, with four studies selected for oral presentation, and one study awarded the YoungEHA Best Abstract Award, making it one of the four global award-winning studies of the year and the only one from China to receive this honor. This achievement not only highlights the team's exceptional strength but also showcases the potential and capabilities of Chinese researchers. "Oncology Frontier - Hematology Frontier" specially invited Professor Xiaohui Zhang and his team members for a roundtable discussion to share their research findings, covering non-invasive diagnostic techniques, mechanisms of CAR-T cell therapy toxicity in relapsed/refractory T-cell leukemia, prognosis models for mixed phenotype acute leukemia (MPAL), and innovative clinical research in immune thrombocytopenia (ITP).
Invited Oral Presentation 3
S266 – Prognostic Model Development and Validation for MPAL Patients Treated with Allo-HSCT
Professor Xiaohui Zhang presented the oral lecture.
Background: Mixed phenotype acute leukemia (MPAL) is a rare but dangerous type of acute leukemia. Currently, no optimal treatment regimen is fully established, but allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a promising treatment option with encouraging long-term survival rates. However, there are no definitive indicators for which MPAL patients can undergo allo-HSCT. This study investigates the clinical characteristics and prognosis of MPAL patients receiving allo-HSCT in a national multicenter cohort.
Objective: To develop and validate a prognostic model based on patient characteristics, clinical biomarkers, and transplant information that can predict survival and prognosis outcomes for MPAL patients treated with allo-HSCT.
Methods: The retrospective study analyzed 201 newly diagnosed MPAL patients who received allo-HSCT as consolidation therapy from 27 hospitals nationwide between 2008 and 2022. Immunophenotype reports were reviewed to ensure compliance with WHO MPAL standards. Researchers divided 114 patients into the derivation cohort and 87 patients into the external validation cohort. The study included patient characteristics, clinical biomarkers, and transplant information as potential risk predictors. First, univariate associations between each variable and mortality were calculated in the derivation cohort. Variables with P values less than 0.1 in the univariate analysis were further included in multivariate analysis using forward stepwise Cox regression modeling. Independent prognostic factors were identified based on the final multivariate analysis results in the derivation cohort. The prognostic model was generated using coefficients associated with each potential predictor estimated by multivariate Cox regression. Model performance was evaluated by assessing discrimination (area under the curve [AUC]), calibration (calibration plots), and net benefit (decision curve analysis [DCA]).
Results: During the study period, 201 MPAL patients received allo-HSCT, with a 3-year overall survival (OS) rate of 75.1% (95%CI: 68.6-80.9). Using stepwise variable selection in multivariate Cox regression, four highly significant independent prognostic factors for allo-HSCT mortality were identified: platelet count at diagnosis (PLT) (P<0.001; OR 0.99; 95%CI: 0.99-1.00), fibrinogen (P=0.611; OR 0.91; 95%CI: 0.63-1.31), cytogenetics (P=0.005; OR 2.28; 95%CI: 1.28-4.06), and conditioning regimen (P=0.060; OR 0.55; 95%CI: 0.3-1.03). Based on the regression coefficients, a risk stratification model was constructed. PLT<100×10^9/L and fibrinogen<2 g/L were each assigned 1 point, high-risk cytogenetics and myeloablative conditioning were assigned 2 points. The overall risk score was obtained by summing the points, dividing patients into low-risk (0-3 points) and high-risk groups (4-6 points). The model demonstrated satisfactory discrimination and calibration. Decision curve analysis indicated clinical implementation of the prognostic model could benefit MPAL patients. Kaplan-Meier survival estimates showed good separation between risk groups.
Conclusion: This study developed and externally validated a comprehensive prognostic model, the first to combine clinical and laboratory risk factors for evaluating mortality in MPAL patients treated with allo-HSCT. The model can effectively aid pre-transplant risk assessment and stratification and assist in decision-making regarding allo-HSCT.
Dr. Zhuoyu An: Our team recently compiled data from 27 national multicenter sites to conduct an in-depth investigation into acute mixed phenotype leukemia, a rare but poor-prognosis disease subtype. In this study, we proposed a scoring system to predict the prognosis of hematopoietic stem cell transplantation for acute mixed phenotype leukemia. This research achievement was honored to receive the YoungEHA Best Abstract Award this year, making it one of the four international award-winning studies and the only one selected from China. We look forward to future research further guiding the diagnosis and treatment of acute mixed phenotype leukemia, bringing more hope to patients.
Invited Oral Presentation 4
S317 – Zanubrutinib Combined with Eltrombopag as Second-Line Therapy for Immune Thrombocytopenia: An Open-Label, Randomized, Phase II Clinical Trial
Professor Xiaohui Zhang presented the oral lecture.
Background: Immune thrombocytopenia (ITP) is an acquired immune-mediated disease characterized by isolated thrombocytopenia, where loss of immune tolerance leads to increased platelet destruction and reduced platelet production. First-line treatments, such as corticosteroids and intravenous immunoglobulin (IVIg), have relatively low long-term remission rates. Although various subsequent treatments, including thrombopoietin receptor agonists, rituximab, recombinant human thrombopoietin, and splenectomy, are available, none guarantee durable responses or long-term remission. Managing refractory/relapsed patients remains a challenge. Bruton’s tyrosine kinase (BTK), a member of the Tec tyrosine kinase family, is widely expressed in many cell types. BTK plays a major role in immune responses, acting as a key mediator of B-cell receptor (BCR) and Fcγ receptor signaling. Recently, Kuter et al. reported that the oral BTK inhibitor rilzabrutinib achieved an overall response rate of 40% as a second-line treatment for refractory ITP. Researchers’ previous studies showed that another oral BTK inhibitor, zanubrutinib, at 80 mg daily for six weeks, achieved a 35% sustained response with minimal adverse events. Based on these findings, researchers hypothesized that zanubrutinib might be a better second-line treatment for refractory ITP.
Objective: To evaluate the efficacy and safety of zanubrutinib in treating refractory ITP.
Methods: The study recruited patients aged 18-70 years with two platelet counts below 30×10^9/L within 15 days before enrollment (at least seven days apart) and who did not achieve sustained remission after receiving full-dose corticosteroid treatment for at least four weeks or relapsed after dose reduction or discontinuation. Patients were randomly assigned to the intervention group and control group. The intervention group received zanubrutinib 80 mg daily for six weeks and eltrombopag 50 mg daily for up to six weeks. The control group received eltrombopag at the same dose. During treatment, eltrombopag doses in both groups were adjusted based on platelet counts. Study visits were scheduled weekly for the first six weeks, then biweekly until six months, and monthly until 12 months. The primary endpoint was overall response (OR), defined as at least two consecutive platelet counts of at least 50×10^9/L, at least double the baseline count, without bleeding, and without requiring rescue treatment at six weeks. The trial is registered at ClinicalTrials.gov (NCT05369377).
Results: From October 30, 2022, to December 31, 2023, 75 patients were screened for eligibility; four were excluded, and 71 were randomly assigned: 35 in the intervention group and 36 in the control group. During the 12-month follow-up, patients receiving zanubrutinib plus eltrombopag achieved a higher overall response rate [27 of 35 (77.1%) vs. 20 of 36 (55%), odds ratio 2.12, 95% CI: 1.5-6.02; P<0.05] compared to those receiving eltrombopag alone. All patients tolerated the treatment well, with no need for treatment interruption or dose reduction.
Conclusion: Zanubrutinib combined with eltrombopag showed encouraging response rates and tolerability in patients with refractory ITP. This finding suggests that BTK inhibitors like zanubrutinib could be promising candidates for patients with corticosteroid-resistant or refractory primary immune thrombocytopenia.
Dr. Chencong Wang: Our team’s report focuses on the efficacy of zanubrutinib combined with eltrombopag as a second-line treatment for corticosteroid-resistant and relapsed ITP patients. We have conducted a randomized, phase II clinical trial, showing that zanubrutinib might have better second-line treatment efficacy for corticosteroid-resistant ITP patients, providing valuable guidance for future medication use in such patients.
Expert Commentary
Professor Xiaohui Zhang: The 29th Annual Meeting of the European Hematology Association (EHA) opened grandly in Madrid, Spain, in 2024. This year, our team was honored to have four oral presentation opportunities, covering academic achievements in several fields, including malignant hematological tumors. These mainly include hematopoietic stem cell transplantation, cell therapy (especially CAR-T therapy), and processes of humoral immunity and precision diagnostics. We also reported on clinical research in immune thrombocytopenia and coagulation disorders.
The results we presented to the conference initially showcased the work of Peking University People’s Hospital under the leadership of Academician Xiaojun Huang. These studies have emerged in the integration of technology and clinical research, not only stepping onto the international stage, demonstrating the innovative design and originality of Chinese researchers but also receiving positive evaluations from international peers and experts in the hematology field. We feel very honored by this recognition.
2024 CSH and EHA Online and Offline Work Exchange Meetings
