Recently, the 11th Sino-French Hematology Academic Conference of the Chinese Medical Doctor Association was successfully held in Tianjin, attracting hundreds of domestic and international authoritative experts and scholars in the field of hematology. During the conference, "Hematology Frontier" specially invited Dr. Norbert Claude Gorin from Hôpital Saint-Antoine in Paris, a member of the French National Academy of Medicine, and a foreign academician of the Chinese Academy of Engineering, to discuss the evolution of the role of autologous transplantation in the treatment of acute myeloid leukemia (AML) and the challenges and potential of immunotherapy in AML treatment.

Hematology Frontier: Given the historical significance of autologous transplantation in AML treatment, how do you envision the future role of this approach evolving amidst the emergence of novel drugs and immunotherapies?

Dr. Norbert Claude Gorin: In the treatment of acute myeloid leukemia , allogeneic hematopoietic stem cell transplantation is often considered the most effective post-remission treatment method. It primarily relies on the graft-versus-leukemia effect, which involves an immune response by donor T cells against tumor surface antigens to eliminate leukemia cells. However, this process can be toxic, and sometimes the intensity of the treatment needs to be reduced to mitigate this toxicity.In contrast, autologous hematopoietic stem cell transplantation has the advantages of no donor restrictions, no graft-versus-host disease , and low transplant-related mortality. However, its anti-tumor effect is relatively weak. With the emergence of new drugs and immunotherapies, the future role of ASCT may evolve. On one hand, ASCT can serve as a treatment option for patients who are not suitable for allo-HSCT. For those who cannot find a suitable donor or cannot tolerate the high-intensity treatment of allo-HSCT, ASCT still has value. On the other hand, combining immunotherapy is expected to make up for the weakness of ASCT’s anti-tumor effect and enhance the anti-tumor immune response after ASCT. Currently, strategies combining ASCT with immunotherapy are being explored, aiming to achieve the same therapeutic effects as allo-HSCT while reducing side effects and improving patients’ quality of life. The exploration and optimization of this strategy are undoubtedly one of the important directions for future AML treatment research.In summary, the emergence of new drugs and immunotherapies has brought new opportunities and challenges to AML treatment. Autologous transplantation still has its value in specific patient populations, and by combining with emerging therapies, it may continue to play an important role in AML treatment in the future.

Hematology Frontier: What are the potential advantages or challenges of immunotherapies such as CAR-T cell therapy or immune checkpoint inhibitors in reviving autologous transplantation as a treatment modality for AML?

Dr. Norbert Claude Gorin: Immunotherapy holds significant promise in the treatment of acute myeloid leukemia , with immune checkpoint inhibitors such as anti-CD47 monoclonal antibodies enabling macrophages to target and eliminate AML cells. This approach enhances the immune system’s attack on cancer cells by blocking immunosuppressive signals. CAR-T cell therapy involves genetically engineering a patient’s T cells to recognize and destroy specific cancer cells, including those of AML. These treatments offer precision medicine, reducing damage to healthy cells and potentially leading to long-term disease control.However, immunotherapy in AML faces considerable challenges. One is identifying suitable targets, as antigens on AML cells may also be expressed on normal hematopoietic stem cells, risking treatment-related toxicity. Secondly, immune evasion can occur as tumor cells may downregulate the expression of target antigens to escape immune attacks. Additionally, immunotherapy can cause severe side effects, such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome , which require close monitoring and proper management.In summary, while immunotherapy shows tremendous potential in AML treatment, it also needs to overcome several challenges. Future research may focus on developing safer and more effective immunotherapeutic strategies and how to combine these with other treatment modalities, such as chemotherapy, to improve treatment outcomes and quality of life for AML patients.

Hematology Frontier: What clinical trials are currently underway that combine immunotherapy with autologous transplantation strategies, and what are the anticipated impacts of these trial results on AML treatment?

Dr. Norbert Claude Gorin: As far as I know, in the treatment of acute myeloid leukemia , the MyloFrance-1 single-arm phase II study evaluated the efficacy of gemtuzumab ozogamicin monotherapy in adult patients with CD33-positive AML at first relapse. The study involved 57 patients with a median age of 64 years (ranging from 22 to 80 years), and the complete remission rate was 26%, with a median relapse-free survival of 11.6 months. These results suggest that gemtuzumab ozogamicin can be an effective treatment option for this patient population .As more clinical trials are conducted and their results are published, we can anticipate that the therapeutic strategy combining immunotherapy with autologous transplantation will continue to be optimized and refined in the treatment of AML. This approach holds the potential to offer more hope and better therapeutic outcomes for AML patients.