18P Adoptive cell therapy (ACT) with bispecific gamma delta TCR+ invariant TCR+ NKT-like cells for multiple myeloma (MM): Comparison of preconditioning (PC) on outcome

Abstract

AVM0703 (AVM) is the subject of an actively enrolling US trial in relapsed/refractory (R/R) no-option Non-Hodgkin’s Lymphoma (NHL), with drug related adverse events limited to grades 1-3 and durable complete (CR) and partial responses (PR) to date. Acute supra-pharmacologic doses (>6 mg/kg) of AVM0703 mobilized endogenous bispecific gdTCR+ invTCR+ Natural Killer T-like cells (AVM_NKT) (PCT/US21/19773) in mice, humanized mice and clinical trial patients1. An ACT model was conducted to verify the direct tumor killing activity of AVM0703 induced novel immune cells (AVM_NKT) and to determine the effect of different PC on tumor killing of the ACT. MOPC315 (Balb/c) MM cells were inoculated into the flank as single cell suspensions. When tumor volume reached ∼400mm3 well-established tumors, mice were PC’d with human equivalent dose (HED) cyclophosphamide-fludarabine (CyFlu HED 500/30 mg/mm2), with Placebo (PL) or with AVM0703 HED 18 mg/kg. ACT splenocytes (3.3M) from mice dosed with PL or AVM were iv injected 48 hours later (PL_ACT had 8,240 AVM_NKT and AVM_ACT had 150,000). The next day (13-16 hours later) the mice were euthanized and remaining live MOPC cells were measured in the tumor, spleen, bone marrow, thymus and blood by flow cytometry. PC was necessary for AVM_ACT effect since there was no difference in live MOPC cells between AVM_ACT versus PL_ACT in mice PC’d with PL. AVM PC was equivalent to CyFlu PC against MOPC in tumor and spleen when AVM_ACT were transferred. Neither AVM nor CyFlu PC (with AVM_ACT) reduced MOPC in blood, bone marrow or thymus compared to PL PC. Repeat daily AVM and CyFlu dosing for PC will be explored in subsequent studies.Table: 18PPCPlaceboAVMAVMCyFluCyFluACTAVMPlaceboAVMPlaceboAVM* P<0.05 versus Placebo PC with Placebo ACTTumor***Spleen***BloodBone marrow*Thymus Open table in a new tab AVM0703 could be a less-toxic PC agent before CarT or other ACT. 1 Blood 2021:138(S1) 4557