Abstract 6471: Immune correlates post MMF omission lead to accelerated immune reconstitution without increased graft versus host disease risk signatures for allogenic stem cell transplant (OmitMMF trial)

Abstract Mycophenolate mofetil (MMF) has been a standard practice of care used in combination with post-transplant cyclophosphamide (PTCy) in graft-versus-host-disease (GvHD) prophylaxis regimen. This study evaluated the safety and potential benefits of eliminating MMF in patients receiving reduced-intensity (RI) and myeloablative (MA) conditioning with fludarabine and total body irradiation (FluTBI) prior to peripheral blood stem cell transplants (PBSCT) from matched or haploidentical related, or match unrelated, donors. The outcomes of 60 study subjects were compared to time-matched historical control patients. As we have previously presented, relapse-free survival at 1 year and viral reactivation by day +100 was not different in OmitMMF patients and control patients. While there were no significant clinical differences between treatment arms, we explored whether omitting MMF had significant effects on immune reconstitution. We used a 42-color spectral flow cytometry to characterize T-cells, NK-cells, B-cells, and monocytes. High dimensional clustering was performed using Phenograph to identify T-cell activation state clusters and other granular cell populations. OmitMMF patients had a higher number of T-cells at days +15 and +30, but lower by day +60. This increase was due to increased CD4+ T-cells in the OmitMMF patients and not CD8+ T-cells. Effector CD4+ T-cells were significantly higher while naïve CD4+ T-cells were not different. NK-cells were not significantly different between the two groups, contrasting the published effects of MMF on NK-cell function suggesting an anti-proliferative effect. While NK-cells were higher in the control arm at day 60, this was after MMF was removed and may represent a rebound affect. B-cells were not significantly different between the two groups. Omitting MMF led to faster CD4+ recovery as MMF suppresses CD4+ T-cell proliferation without adding greater risk of developing GvHD. Within the OmitMMF cohort, immune recovery was compared between patients who developed GvHD and those who did not. No distinct early immune correlates, such as a higher CD4+ T-Cells or different NK-cell count, were observed in the patients who developed GvHD, suggesting that omitting MMF reduces immunosuppression without leading to the T-cell signatures that are associated with a higher GvHD risk. Interestingly, the rate of grade II-IV aGVHD was significantly higher in the OmitMMF patients who received MA conditioning than the control group; this is dependent on preconditioning and is being further evaluated with the flow cytometry data. In conclusion, MMF can be safely eliminated in patients receiving RI and MA FluTBI conditioning regimens with the PTCy+tacro prophylaxis, and allows for quicker early T-cell recovery without causing harmful immune overactivity. Citation Format: Vanshika Chauhan, Joseph Lownik, Larry Milshteyn, Haein Kim, Ronald Paquette, Akil Merchant. Immune correlates post MMF omission lead to accelerated immune reconstitution without increased graft versus host disease risk signatures for allogenic stem cell transplant (OmitMMF trial) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6471.