Editor’s Note: The 28th European Hematology Association (EHA) Congress, held from June 8th to June 11th, 2023, in Frankfurt, Germany, presented a combination of online and offline formats. As the largest international congress in the European hematology field, EHA featured various scientific topics, covering benign and malignant hematology and discussing the latest advancements in the field. With a focus on the treatment of Acute Lymphoblastic Leukemia (ALL), particularly in the realm of immunotherapy, Oncology Frontier had an exclusive interview with Dr. Ma Jun from the Harbin Institute of Hematology and Oncology, China, who provided insightful commentary.
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Oncology Frontier: Would you please briefly summarize the international status of Acute Lymphoblastic Leukemia (ALL) treatment?
Dr. Ma Jun: According to current international data, the clinical cure rate for children with high-risk Acute Lymphoblastic Leukemia (ALL) is around 92%. Even for high-risk cases, the cure rate reaches 78%-80%. Consequently, childhood ALL has become a curable malignant tumor. In contrast, treating adult ALL, especially in elderly patients, remains challenging. While inducing a remission rate of over 90%, the long-term survival is extremely grim. Data shows that after the first relapse in adult ALL patients, the survival period is merely 3-5 months, further declining after subsequent relapses.
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Oncology Frontier: What are the key research directions in Acute Lymphoblastic Leukemia (ALL) treatment at this EHA Congress?
Dr. Ma Jun: Adult Acute Lymphoblastic Leukemia (ALL) treatment has emerged as a vital research focus in recent years. At this EHA Congress, the primary research focus in ALL treatment was immunotherapy, including monoclonal antibodies, antibody-drug conjugates (ADCs), bispecific antibodies, and cell immunotherapy like CAR-T treatment. Particularly notable was the use of CD19/CD3 bispecific antibodies (Blinatumomab) as bridging therapy for MRD-positive Ph+ ALL patients before Allo-HSCT, showing remarkable efficacy. In cell immunotherapy, CAR-T is increasingly employed for treating relapsed/refractory B-cell Acute Lymphoblastic Leukemia (r/r B-ALL), achieving significant success. To emphasize, the exploration of Acute Lymphoblastic Leukemia (ALL) treatment became a crucial focal point at this conference, stressing standardization, precision, and individualized treatment. For MRD-positive ALL patients, frontline application of CD22 monoclonal antibodies aims to eradicate MRD for longer survival. Moreover, post-CD22 monoclonal antibody treatment, bridging to Allo-HSCT shows a success rate of over 60% in relapsed/refractory ALL patients, leading to higher disease-free survival rates. If used as a frontline treatment to clear MRD, the 3-year progression-free survival (PFS) reaches nearly 68%-72%. Similarly, CD19/CD3 bispecific antibodies also exhibit significant efficacy in MRD clearance and bridging to transplantation. However, caution is warranted during CD22 and CD19/CD3 bispecific antibody treatments due to potential adverse effects. CD22 monoclonal antibody treatment plus transplantation requires monitoring for hepatic veno-occlusive disease (VOD), preventable with pretransplantation use of defibrotide and low-molecular-weight heparin. Adverse effects associated with CD19/CD3 bispecific antibodies are predominantly cytokine release syndrome (CRS) and neurologic events (NE), requiring clinical attention.
In treating adult relapsed/refractory B-cell ALL (r/r B-ALL), CD19/CD22 bispecific CAR-T has shown impressive efficacy, with studies indicating an objective response rate (ORR) of up to 100%, reaching 88% for CR+CRh+CRi. This bispecific CAR-T therapy has made significant progress domestically and is even approaching international standards, potentially matching the effectiveness of Allo-HSCT in treating r/r B-ALL. It’s expected to be approved for domestic use soon. Overall, antibody-drug conjugates (ADCs), monoclonal antibodies, bispecific antibodies, and CAR-T therapy have surged in ALL immunotherapy. Regarding treatment choice, CAR-T and Allo-HSCT are the primary methods to cure the disease. ADCs, monoclonal antibodies, and bispecific antibodies elevate complete remission rates, serving as vital approaches to successful transplantation bridging.
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Oncology Frontier: What is the main progress of treatment in T-cell Acute Lymphoblastic Leukemia (T-ALL)?
Dr. Ma Jun: The incidence rate of T-cell Acute Lymphoblastic Leukemia (T-ALL) is lower than that of B-cell ALL, and treatment efficacy and progress lag comparatively. In China, regardless of children or adult patients, some individuals have very low cure rates for ALL, necessitating treatment and cure through Allo-HSCT. Presently, studies indicate that Nelarabine exhibits significant efficacy in treating T-cell ALL. Nelarabine combined with chemotherapy can achieve a complete remission rate (CR) of over 90% and an overall survival (OS) of up to 62% in 18 months. Hence, Nelarabine has become a crucial drug for T-cell ALL or T-cell lymphoma, and its early approval in China is anticipated to improve the survival and prognosis of T-cell ALL patients, especially those with relapsed/refractory T-cell ALL.
TAG: EHA 2023, Interview, Hematological Malignancy, ALL
