Introduction:

Recent studies have shown the safety and feasibility of abatacept (ABA) addition to post-transplant cyclophosphamide (PTCy) and tacrolimus (TAC) for graft versus host disease (GVHD) prophylaxis after matched (MUD), mis-matched unrelated donor (MMUD) and haploidentical (Haplo) peripheral blood allogeneic HCT. However, there is limited data comparing the outcomes of PTCy with ABA/TAC vs PTCy with Mycophenolate/TAC.

Methods

We retrospectively reviewed the outcomes of 99 consecutive patients with high-risk hematological malignancies who received mobilized peripheral blood HCT with PTCy based GVHD prophylaxis between January 2021 and April 2025. ABA was initially added to PTCy/TAC in MUD and MMUD HCTs in January 2023 then Haplo HCT in May 2023. ABA was dosed at 10 mg/kg on D-1, +5, +14 and +28. All patients received PTCy at dose of 50 mg/kg on D+3 and +4 in MMUD and haplo patients and at reduced dose of 25 mg/kg in > 8/8 MUDs. Before this institutional change all patients received PTCy as above on D+3 and +4 in combination with TAC and mycophenolate (MMF) starting D+5.

Results:

Sixty-six patients received TAC/ABA/PTCy (TAP group), and 33 patients received TAC/MMF/PTCy (TMP group). The median age for the TAP group was 58 years (range 23-77) and 57 years (range 23-73) for the TMP group. There were 37 males and 29 females in the TAP group compared to 16 males and 17 females in TMP group (P= 0.64). There were no statistical differences in CMV status of the donors or recipients between two groups with P values 0.92 and 0.46 respectively. Conditioning regimens were FLU-BU based in 16 and 11 patients (P=0.42), FLU-MEL based in 32 and 14 patients (P=0.69) and FLU-CY-TBI in 17 and 8 patients (p=0.9) in the TAP and TMP groups respectively. All patients received institutional standard of care antimicrobial prophylaxis.

The two groups were well balanced except for more AML patients in the TAP group (42 vs 11, P= 0.047), more haploidentical in the TMP group (12 vs 12, P= 0.09) and more MUDs in the TAP group (38 vs 11, P=0.1). The TAP group had 42 AML, 8 ALL, 11 MDS, 1 MF, 1 BPDCN, 1 CML, and 2 HTLV-1 ATLL. The TMP group had 11 AML, 7 ALL, 7 MDS, 1 HTLV-1 ATLL, 2 R/R DLBCL, 2 R/R T-cell lymphoma and one patient each with CML, MF and Hodgkin disease. Disease status at the time of transplant for TAP and TMP groups included primary refractory/relapsed in 21% vs 31% (P=0.27), complete remission in 58% vs 37% (P=0.2), and stable disease in 19% vs 25% (P=0.45) respectively. A TP53 mutation was found in 25.4% vs 20% (P=0.68) in the TAP and TMP groups respectively. Comorbidity scores of 0-2, 3-4, and > 5 were 35.8%, 25.4% and 38.8% in the TAP group and 42.9%, 25.7% and 25.7% in TMP group respectively (P= 0.42, 0.87 and 0.34).

The median duration of follow up was 393 days (105-937) for the TAP group and 748 days (910-1645) for the TMP group as of July 30, 2025. All patients engrafted and acheived full donor Chimerism by day 30 except for one patient with primary graft failure in TMP group who was rescued with a MUD transplant. The median neutrophil recovery was 13 days (range 11-18) in TAP and 15 days (range 11-34) in TMP. There was an overall survival (OS) advantage for the TAP group at D+100 and 1 year of 98.5% and 84.8% vs 87.9% and 69.7% for the TMP group (P=0.019). There was no difference in the cumulative incidence of relapse at D+100 and 1 year at 12% and 27.8% vs 9% and 33% for TAP and TMP groups respectively (P=0.77). There was a trend toward improved TRM in the TAP group with a cumulative incidence of 0% at D+100 and 6% at 1 year, while the cumulative incidence of TRM in the TMP group was 9% and 15% at D+100 and 1 year (P=0.08).

We found a lower risk of acute GVHD in TAP group with cumulative incidence of 33.3% vs 51.5% in TMP group (P=0.04). Acute GVHD cases in the TAP group were grade 1/2 only while there were 3 patients with grade 3 in the TMP group. In contrast, the cumulative incidence of chronic GVHD was 66.2 % in the TAP group vs 39.4% in TMP group at 1 year( P=0.07). Severe extensive chronic GVHD only occurred in 5 patients in each group (7.5% for TAP and 15.1% for TMP), Chronic GVHD was the cause of death in 4 patients in each group (6% for TAP vs 12% for TMP). Conclusions:

ABA in combination with PTCy and TAC may improve overall survival and decrease the severity of acute GVHD after HCT for hematological malignancies. Future prospective trials are in progress to confirm these findings.

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2025
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