Orca-T Stands Out From CD34 Grafts, Showing Lower Rates of EBV, CMV Reactivation in Hematologic Malignancies

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Lower rates of Epstein-Barr virus (EBV) and cytomegalovirus reactivation occurred when patients with select hematologic malignancies were treated with Orca-T vs a CD34 allograft, according to data from a retrospective comparative analysis presented at the 51st Annual EBMT Meeting.1

The rates of EBV reactivation were 2.3% and 25.4% in the Orca-T and CD34 arms, respectively (P < .001). With respect to CMV reactivation, the respective rates were 1.2% and 25.6% (P < .001). EBV and/or CMV reactivation occurred in 3.5% of patients who received Orca-T vs 45.9% of those who received CD34 grafts (P < .001).

“Significantly reduced EBV and CMV reactivation [was observed] with Orca-T, [which] may be related to increased T-cell counts and donor chimerism in Orca-T patients,” Ioannis Politikos, MD, lead study author and an assistant attending physician at Memorial Sloan Kettering Cancer Center (MSK) in New York, New York, stated during the presentation. “Higher B cells with low T cells early post-transplant in CD34 graft recipients may explain the higher incidence of EBV infections,” Politikos added.

For the analysis, investigators collected data from that Orca-T’s multicenter phase 1b trial (NCT04013685) to constitute the Orca-T patient population. The population of patients who received a CD34 graft were those treated at MSK.

In the Orca-T population, 154 patients received myeloablative conditioning. Of those, 125 had acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndrome (MDS) in complete response (CR), and 123 had 8/8 human leukocyte antigen matches. A total of 86 patients received either busulfan, fludarabine, and thiotepa; total body irradiation and cyclophosphamide; or TBI/VP16 as conditioning.

In the CD34 population, 205 patients received myeloablative conditioning. Of them, 179 had AML, ALL, or MDS in CR, and all had an 8/8 HLA match for donor type. Conditioning regimens included busulfan, fludarabine, melphalan, and antithymocyte globulin (ATG); or cyclophosphamide, thiotepa, TBI1375, and ATG. “ATG use and poor T-cell chimerism early post-transplant complicate the interpretation of T-cell reconstitution in CD34 grafts,” Politikos stated.

Baseline characteristics in the Orca-T (n = 86) population revealed a median age of 48 years (range, 37-57). Most patients in this arm were male (56%) and European (65%). Hematopoietic Cell Transplantation–specific Comorbidity Index scores were 0 (39%), 1 or 2 (29%), 3 or higher (32%), or unknown (n = 1). CMV status was either positive (43%), negative (31%), or unknown/equivocal (26%).

Patients who received Orca-T had AML (51%), ALL (28%), or MDS (21%), and most patients had low- or intermediate-risk disease (72%). Most patients had matched related donors (51%) and underwent busulfan-based conditioning (78%).

Additional results illustrated faster engraftment with the CD34 grafts with respect to both neutrophils and platelets. Neutrophil engraftment occurred at a median of 10 days (range, 10-11) in the CD34 group vs 13 days (range, 12-14) in the Orca-T group. Respective engraftment times for platelets were 16 days (range, 16-17) and 18.5 days (range, 17-19).

Similar leukocyte subset counts were also seen during the first year, post-transplant (Table). The median neutrophil counts in the Orca-T and CD34 cohorts, respectively, at days 28, 56, 100, 180, and 365, were 2.5 vs 3.1, 2.5 vs 3.0, 2.8 vs 2.8, 2.6 vs 2.9, and 2.9 vs 2.8. Monocyte counts in the Orca-T and CD34 arms, respectively, were 0.7 vs 0.7, 0.4 vs 0.5, 0.4 vs 0.5, 0.4 vs 0.4, and 0.4 vs 0.5. Respective lymphocyte counts were 0.6 vs 0.6, 0.6 vs 0.9, 0.6 vs 0.8, 1.0 vs 0.8, and 1.0 vs 1.1.

“The natural killer [NK] cell data can suggest that the presence of conventional/regulatory T cells slows NK cell immune reconstitution, [which may] possibly [be] due to competition for growth factors. Tacrolimus does not seem to play a role given stable levels [between] days 56 and 365,” Politikos concluded.

Disclosures: Politikos has received research funding from Merck and Orca Bio, honoraria from Precisionheor and serves on DSMB for ExcellThera.

Reference

1. Politikos I, Killian S, Chinapen S, et al. Differential immune reconstitution profiles between Orca-T and CD34 allograft recipients provide insight for control of viral infections. Presented at: EBMT 51st Annual Meeting; March 30-April 2, 2025. Florence, Italy. Abstract OS1-05.