Editor's Note: From July 5th to 7th, the highly anticipated 2024 Annual Progress Seminar in Clinical Oncology in China (BOC) and Best of ASCO 2024 China were grandly held in Guangzhou. Based on the actual situation of cancer incidence in China, the conference specially invited authoritative experts in the field of oncology and carefully selected outstanding papers from the 2024 ASCO conference for comprehensive and in-depth interpretation. During the conference, "Oncology Frontier - Hematology Frontier" conducted an exclusive interview with Professor Tiejun Gong from the Harbin Institute of Hematology and Oncology. He shared his profound insights and unique academic perspectives on major studies presented at ASCO this year, the progress of the novel CD3 x CD19 IgG4 bispecific antibody CN201, and the overall status and future prospects of hematologic oncology treatment in China.

Oncology Frontier – Hematology Frontier: At this conference, you shared three significant studies in the field of hematologic oncology presented at ASCO this year. First, could you briefly introduce the background and main findings of LBA 6508 (Multi-site randomized trial of a collaborative palliative and oncology care model for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) receiving non-intensive therapy), and discuss its clinical significance?

Professor Tiejun Gong: Research on palliative care and end-of-life care for cancer patients began earlier in the field of solid tumors and has made significant progress. However, research in this area for hematologic malignancies has started relatively late and has progressed slowly. Hematologic malignancies have significant biological and treatment strategy differences compared to solid tumors, especially for advanced patients who need to manage complications like infections and bleeding while coping with anxiety and other emotional issues.

The LBA 6508 study focused on myeloid malignancies, including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The study found that palliative care and end-of-life care are equally important for these patients. This involves not only attention to their quality of life but also their emotional well-being and communication needs with clinicians.

The LBA 6508 study reminds us that hematologic malignancy patients, whether early-stage, advanced, or terminal, need more care and psychological support. The study emphasizes the importance of addressing the overall needs of patients, including emotional health and quality of life, alongside treating the primary disease and complications. This has significant implications for improving patient survival experiences and promoting effective communication between patients and healthcare providers.

In summary, the LBA 6508 study provides new insights into palliative and end-of-life care for hematologic malignancy patients and offers valuable guidance for clinical practice, helping us better serve this patient group.

Oncology Frontier – Hematology Frontier: The subgroup analysis of CARTITUDE-4 explored the treatment outcomes of cilta-cel compared to standard care (SoC) in functional high-risk (FHR) multiple myeloma (MM) patients. Can you share the efficacy of cilta-cel in second-line treatment and whether it offers a new treatment option for FHR MM patients?

Professor Tiejun Gong: The treatment of multiple myeloma has seen significant advancements in recent years, particularly in immunotherapy. CAR-T therapies, including cilta-cel, and upcoming bispecific antibodies, have shown immense potential.

The CARTITUDE-4 study, which I reported on, focused specifically on patients receiving second-line treatment. These patients were treated with cilta-cel, a novel CAR-T therapy. The study covered patients receiving later-line treatments and gradually moved to frontline treatments, including those experiencing first relapse and those after second- or third-line treatments. It evaluated the patients’ response rates, survival outcomes, and quality of life improvements compared to standard care. Overall, the CARTITUDE-4 study encompassed a broad patient population.

I mainly shared the benefits of cilta-cel in terms of response and survival for functional high-risk multiple myeloma patients. The study data showed that cilta-cel demonstrated good efficacy in terms of response rates, progression-free survival (PFS), and the occurrence of adverse events for functional high-risk patients.

Therefore, cilta-cel offers a new treatment option for functional high-risk multiple myeloma patients. This finding not only enriches our understanding of treatment strategies for functional high-risk multiple myeloma patients but also provides clinicians with more treatment options to improve these patients’ prognosis and quality of life. I recommend paying attention to the latest developments in this field.

Oncology Frontier – Hematology Frontier: For the treatment challenge of relapsed/refractory adult acute B-cell lymphoblastic leukemia (R/R B-ALL), how does the novel CD3 x CD19 IgG4 bispecific antibody CN201 perform in terms of safety and efficacy? Can you share the main findings of this study and its potential impact and future development trends in the treatment of this disease?

Professor Tiejun Gong: Immunotherapy has made significant progress in the treatment of R/R B-ALL, including CAR-T therapy, bispecific antibody therapy, and antibody-drug conjugates (ADCs). Among the many marketed products, the novel CD3 x CD19 IgG4 bispecific antibody CN201 stands out due to its structural changes and extended half-life, allowing for unique dosing regimens of once or twice a week. This contrasts with the already marketed CD3 x CD19 bispecific antibody blinatumomab, which requires continuous 24-hour infusion over a 28-day cycle, demonstrating significant advantages. The convenience of this dosing regimen could greatly improve patient adherence to treatment.

In the preliminary Phase I clinical trial (NCT05579132), the overall response rate exceeded 70% at doses up to 20 mg. As the dose increased to 60 mg in Phase II and Phase III trials, and potentially up to 80 mg, the maximum tolerated dose has not yet been reached, indicating the possibility of further dose escalation. At the 60 mg dose level in the Phase I trial, all three patient groups achieved complete remission, showing that the efficacy improves with dose escalation.

In terms of safety, despite dose escalation, the incidence of adverse events did not significantly increase. Cytokine release syndrome (CRS) was manageable, and no immune effector cell-associated neurotoxicity syndrome (ICANS) occurred. The main adverse events were limited to hematologic toxicity and infections, with no other significant hematologic toxicities observed.

Through subsequent clinical trials, we hope that the CN201 bispecific antibody will bring significant clinical benefits to R/R B-ALL patients, regardless of Ph status. We look forward to positive results from Phase II and later studies, which will support the application of CN201 in the treatment of R/R B-ALL, providing patients with a new treatment option.

In summary, the research progress of the novel CD3 x CD19 IgG4 bispecific antibody CN201 brings new hope to R/R B-ALL patients and offers directions for optimizing and innovating future treatment strategies. As clinical research advances, we have reason to believe that this therapy will play a crucial role in improving efficacy and enhancing patients’ quality of life.

Oncology Frontier – Hematology Frontier: Could you discuss the overall status of hematologic oncology treatment in China, including the application value of innovative therapies in clinical practice? What are your prospects for the future development of hematologic oncology?

Professor Tiejun Gong: Although hematologic oncology is a relatively small field within oncology, its development speed is among the fastest. The incidence of hematologic malignancies is lower compared to solid tumors, but the advancements in treatment have been remarkable. Hematologic oncology is at the forefront of cancer treatment, whether in targeted therapies, small molecule therapies, or immunotherapies.

Currently, new drug development is booming, and the field of immunotherapy has made groundbreaking progress. Various treatment methods, including CAR-T cell therapy, ADC drugs, bispecific antibodies, and even trispecific antibodies, are actively being developed. These therapies have shown their respective advantages in treating lymphomas, myelomas, and B-cell acute lymphoblastic leukemia, providing more treatment options for patients at different stages of treatment.

Looking ahead, we expect more immunotherapies to emerge. Additionally, conventional treatments targeting different molecular markers are showing broad clinical application prospects in clinical trials. Notably, many domestic pharmaceutical companies are conducting original clinical trials, which makes us proud and hopeful for the future development of domestic drugs. We hope that hematologic oncology patients can benefit from the rapidly advancing immunotherapies, achieving longer survival and better quality of life.

In summary, the field of hematologic oncology in China is rapidly developing, with new treatment methods and drugs continuously emerging, particularly in the field of immunotherapy, providing more choices for patients. With the active participation of domestic pharmaceutical companies and the advancement of original drug clinical trials, we look forward to bringing more clinical benefits to patients in the future, improving their quality of life and survival.

Professor Tiejun Gong

• Deputy Director of Harbin Institute of Hematologic Oncology
• Member of the Ninth and Tenth Youth Committee of the Hematology Branch of the Chinese Medical Association
• Member of the Hematology Physicians Branch of the Chinese Medical Doctor Association
• Standing Committee Member of the Hematologic Oncology Professional Committee of the Chinese Anti-Cancer Association
• Standing Committee Member of the Hematologic Disease Translation Professional Committee of the Chinese Anti-Cancer Association
• Deputy Director of the Leukemia and Lymphoma Youth Committee of the Chinese Society of Clinical Oncology (CSCO)
• Secretary of the Leukemia Expert Committee and Member of the Lymphoma Expert Committee of CSCO
• Standing Committee Member of the Hematology Institutions Branch of the Chinese Hospital Association
• Member of the Oncology Expert Committee for Capacity Building and Continuing Education, National Health Commission
• Corresponding Editorial Board Member of the “Chinese Journal of Hematology” and Editorial Board Member of “Leukemia & Lymphoma”
• Deputy Director of the Hematology Branch of the Heilongjiang Medical Association
• Deputy Director of the Lymphoma and Myeloma Professional Committee of the Heilongjiang Medical Association
• Deputy Director of the Anti-Leukemia and Lymphoma Alliance of the Chinese Society of Clinical Oncology (CSCO) in Heilongjiang Province