616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Advances in immunotherapeutics for management of AML

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Sameem Abedin, Guru Subramanian Guru Guru Murthy, Mehdi Hamadani, et al.

Authors Conclusion from the Abstract: We conclude that lintuzumab Ac225 in combination with CLAG-M chemotherapy has a clinically acceptable safety profile. Dose escalation yielded highly encouraging efficacy results for RR-AML. With acceptable safety at 0.75uCi/kg, we have amended this protocol to study a 4th dose level at 1.0uCi/kg. Overall, this regimen represents a safe and potentially effective therapy for medically fit RR-AML pts, particularly as a bridge to allogeneic HCT.

Yngvar Floisand, Iris Bigalke, Dag Josefsen, et al.

Authors Conclusion from the Abstract: Administration of autologous DC transfected with PRAME- and WT1-RNA is feasible, safe and well-tolerated. The 2-year 80% survival rate, particularly in the elderly, and the 55% progression-free survival warrant further studies to assess the efficacy of this vaccine approach in improving outcomes in patients with AML.

Naveen Pemmaraju, Giovanni Martinelli, Elisabetta Todisco, et al.

Authors Conclusion from the Abstract: The current available therapy for patients with R/R BPDCN has limited efficacy and significant safety and tolerability concerns that underscore the high unmet need for this patient population. In heavily pretreated R/R BPDCN patients, including patients who had progressed following tagraxofusp, intense chemotherapies and transplant, IMGN632 demonstrated a 30% (n=7) ORR, with 4 CR/CRc responses with notable DORs. In addition, IMGN632 demonstrated a favorable safety profile that included limited grade 3+ TEAEs/SAEs, no cases of CLS, and no deaths. In addition, IMGN632 is given once every 3 weeks, without the need for hospitalization.

This clinical trial represents the largest-to-date prospective group of uniformly treated patients with R/R BPDCN and demonstrates promising activity and favorable tolerability in a cohort of heavily pretreated patients, including nearly half with prior anti-CD123 targeted therapy.

Arjan van de Loosdrecht, Janine van Elssen, Bjørn Tore Gjertsen, et al.

Authors Conclusion from the Abstract: Preliminary data from this ongoing study confirms that vaccination with DCP-001 is able to generate a tumor-specific immune response and may lead to potential tumor control. Two patients were actually converted from being MRD positive at start of vaccination to MRD negative during the study. These patients continue to be in complete remission for at least a year after vaccination. This study continues to enroll patients at a higher vaccine dose of 50.106cells per vaccination and additional data on induced immune responses and MRD status will be shown.

Shelley Herbrich, Natalia Baran, Gheath Alatrash, et al.

Authors Conclusion from the Abstract: We have identified CD200 as a putative stem cell-specific immunomodulatory target that aids in establishing an immunosuppressive microenvironment by significantly suppressing cytokine secretion in response to AML. In a PBMC-humanized mouse model, the presence of cell-surface CD200 was sufficient to protect AML cells from immune-mediated clearance and could be reversed using a blocking anti-CD200 mAb. These findings indicate a utility of CD200 as a novel immune checkpoint target for the development of therapeutic strategies in AML.

Jacqueline S. Garcia, Yael Flamand, Benjamin K. Tomlinson, et al.

Authors Conclusion from the Abstract: In this ongoing phase 1 study in pts with R/R or secondary MDS/AML, DAC plus IPI had expected AE profile and exhibited encouraging clinical activity. The rate of immune-related toxicity was frequent but similar to prior observations with IPI 10 mg/kg for melanoma. Further, high clinical activity was observed amongst pts who did not receive allo-HCT, suggesting that an alloreactive environment may not be required to benefit from CTLA-4 blockade.