P1282: mocravimod improves overall survival in aml patients undergoing allogeneic hematopoietic cell transplantation

Topic: 22. Stem cell transplantation - Clinical Background: Mocravimod (MOC) is a sphingosine-1-phosphate receptor (S1PR) modulator in pivotal stage clinical development for preventing relapse in acute myeloid leukemia (AML) patients (pts) undergoing allogeneic hematopoietic cell transplantation (allo-HCT). The success of allo-HCT is limited by leukemia relapse, which is closely related to overall survival (OS), and graft-versus-host disease (GvHD). Graft-versus-leukemia (GvL) effect is essential to prevent disease relapse. Pharmacological modulation of S1PR signaling by MOC efficiently sequesters T cells in lymphoid organs and thus possibly reduces GvHD and enables a therapeutic benefit of MOC via donor T cell-mediated GvL against the leukemic cells. Study CKRP203A2105 (NCT01830010) investigated the safety and tolerability of MOC in patients with hematological malignancies undergoing allo-HCT. Aims: To explore relapse and survival outcomes for the subgroup of AML pts included in the CKRP203A2105 (A2105) study in comparison to a control group of AML pts undergoing allo-HCT who did not receive MOC treatment during the same time at one study site. Methods: 7 AML pts were included in CKRP203A2105 across three treatment arms (3mg MOC+cyclosporine (CsA)/methotrexate (MTX) (part 1), 1mg MOC+CsA/MTX and 3mg MOC+tacrolimus (Tac)/MTX (part 2)). During the same period nine AML pts underwent allo-HCT at one of the study sites outside of the trial, thus without MOC. These nine patients were selected based on the same criteria as study pts and were used as the control group. Follow-up period was up to 1 year in part 1 and up to 2 years in part 2. Further follow-up information for individual pts could be collected after obtaining informed consent for this follow-up study. Bayesian comparison of OS of MOC-treated AML pts and controls was performed. Results: Pts demonstrated comparable baseline characteristics with a median age of 51 years in the MOC group versus 46 years in the control group, and a pre-allo-HCT remission state of CR in 4 (57.1%) in the MOC treated pts vs 4 (44.4%) in the control group. More pts were male, 5 (71.4%) in the MOC group vs 3 (33.3%) in the controls. Only 2 pts in the MOC arm died prior to censoring (approximately at 2.5- and 5-years post allo-HCT) (Figure 1), compared to 6 pts in the control group. 1 of these 2 pts relapsed after 2 years and died 4 months later, while the other pt died without relapse. A Bayesian comparison of the survival curves of the MOC pts and the control group suggested a 93% probability that MOC increased the OS compared to the control group. Figure 1: Individual survival timesSummary/Conclusion: Taken together, this post hoc analysis suggests a possible survival benefit for AML pts undergoing allo-HCT who receive an additional treatment with MOC. Only 1 AML pt relapsed whilst being on MOC treatment. This further supports the development of MOC as an adjunctive and maintenance treatment to allo-HCT in a homogeneous AML patient population and provides a rationale for a treatment period of 12-months for MOC which will be investigated further in the current MO-TRANS trial (NCT05429632). Keywords: Allogeneic stem cell transplant, Acute myeloid leukemia, Graft-versus-leukemia, Graft-versus-host disease (GVHD)