AlloHSCT is a potentially curative therapy for hematological malignancies, but the prognosis for many patients remains poor

  • Survival post-transplant is still limited by the balance of efficacy vs toxicity, including GVHD, organ failure, and infection1*
  • Immunosuppression may reduce GVHD risk; however, it can increase the risk of relapse and infection and introduce toxicities that may interfere with transplant success2*

Causes of death after alloHSCT1†

NRM, including GVHD, accounts for the majority of deaths

Current GVHD prophylaxis for alloHSCT has significant limitations

GVHD prophylaxis with MTX is associated with delayed engraftment, serious infections, severe mucositis, hepatotoxicity, and nephrotoxicity3,4

In a prospective, randomized trial of 92 patients that compared Tac/MTX vs Tac/MMF for GVHD prophylaxis following conventional alloHSCT, Tac/MTX resulted in4:

Slower neutrophil engraftment
(16 vs 15 days, P=.29)

Slower platelet engraftment
(17 vs 15 days, P=.002)

Higher incidence of Grade 3 or 4 mucositis
(53% vs 33%, P=.06)

Longer hospitalization after transplant
(19 vs 17 days, P=.04)

There were no significant differences in relapse (P=.21), NRM (P=.62), OS (P=.58), or RFS (P=.49) between the Tac/MTX and Tac/MMF treatment arms.4

GVHD prophylaxis with PTCy may require a tradeoff between efficacy and toxicity5,6

In the prospective, multicenter phase 3 BMT CTN 1301 trial of 232 patients who received GVHD prophylaxis with PTCy (n=114) or Tac/MTX (n=118) after a bone marrow graft5,6§:

  • Prophylaxis with PTCy had similar outcomes to Tac/MTX as measured by survival free of moderate-to-severe chronic GVHD and disease relapse (CRFS)
  • PTCy demonstrated better chronic GVHD control, but greater potential for infections and delayed engraftment
Endpoints PTCy, % Tac/MTX, %
OS at 2 years 76.2 76.1
Transplant-related mortality at 2 years 15.7 7.9
CRFS at 2 years 48.1 41.0
Moderate or severe chronic GVHD at 2 years 27.0 33.7
Grade 2-4 acute GVHD by 100 days 37.6 29.8
Grade 3-4 acute GVHD by 100 days 10.1 3.5
Delayed engraftment 8.3 3.5
Grade 3 infections (cumulative incidence at 2 years) 20.2 14.0

In a single-center prospective analysis (across 7 clinical trials) of 286 patients undergoing alloHSCT with PTCy GVHD prophylaxis, 48% had Grade 1-4 cardiac AEs (Day 0 to Day 100), and the cumulative incidence of Grade ≥3 cardiac AEs was 7.4% at Day 50, most commonly (≥5 patients) heart failure, arrhythmia, and pericardial effusion.7

*CIBMTR data are inclusive of patients treated with CNI+MTX for GVHD prophylaxis.1
†Data from 37,655 adults aged ≥18 years compiled by CIBMTR. All patients received their first allogeneic HCT/CT in the US between 2014 and 2024 as reported to CIBMTR. Causes of death were summarized using frequencies.1
‡Data reflect 10-year mortality.1
§Multicenter phase 3 trial randomly assigned patients with acute leukemia or myelodysplasia and an HLA-matched donor to receive CD34-selected peripheral blood stem cell, PTCy after a bone marrow graft, or Tac/MTX after bone marrow graft (control).5
 AE, adverse event; alloHSCT, allogeneic hematopoietic stem cell transplant; CIBMTR, Center for International Blood and Marrow Transplant Research; CNI, calcineurin inhibitor; CRFS, survival free from moderate-to-severe chronic GVHD and disease relapse; CT, cell transplant; GVHD, graft-versus-host disease; HCT, hematopoietic cell transplantation; HLA, human leukocyte antigen; MMF, mycophenolate mofetil; MTX, methotrexate; NRM, non-relapse mortality; OS, overall survival; PTCy, post-transplant cyclophosphamide; RFS, relapse-free survival; Tac, tacrolimus.
Next: discover what makes tregzi different

IMPORTANT SAFETY INFORMATION AND INDICATIONS AND USAGE

ISI tray

ISI tray

INDICATIONS AND USAGE

TREGZI is indicated for use in matched donor hematopoietic stem cell transplantation with myeloablative preparative regimen, for hematopoietic and immunologic reconstitution and to improve chronic graft-versus-host disease-free survival, in the treatment of adults with hematological malignancies.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Graft Failure: Graft failure has occurred after TREGZI administration. Screen TREGZI recipients for antidonor antibodies that may prevent engraftment. Monitor patients closely for laboratory evidence of hematopoietic recovery.

Graft-Versus-Host Disease: Acute and chronic Graft-Versus-Host disease (GVHD), including life-threatening and fatal cases, occurred following treatment with TREGZI. Acute GVHD manifests as maculopapular rash, gastrointestinal symptoms, and elevated bilirubin. Chronic GVHD may include skin rash, mouth sores, dry eyes, liver inflammation, and development of scar tissue in the skin and joints and damage to the lungs. Treat patients with a single agent calcineurin inhibitor as prophylaxis to decrease the risk of GVHD. Monitor for signs and symptoms of GVHD, and treat if GVHD develops.

Infusion Reactions: Infusion reactions (IRs) may occur during or following treatment with TREGZI. Serious hypersensitivity reactions including anaphylaxis may occur to DMSO, human serum albumin (HSA), Dextran or murine protein present in TREGZI. IRs may begin within minutes of the start of TREGZI infusion, although symptoms may continue to intensify and not peak for several hours after the completion of the infusion. Monitor patients for signs and symptoms of IRs during and after TREGZI administration. When a reaction occurs, pause the infusion and institute supportive care as needed. Premedicate patients with antipyretics and histamine antagonists prior to infusion to reduce the incidence and intensity of infusion reactions.

Secondary Malignancies and Malignancies of Donor Origin: Secondary malignancies and malignancies of donor origin may occur following treatment with TREGZI. Development of secondary malignancies, including posttransplantation lymphoproliferative disorder (PTLD) may occur many years after transplantation. PTLD manifests as a lymphoma-like disease favoring non-nodal sites. PTLD is usually fatal if not treated. Serial monitoring of blood for EBV DNA may be warranted in patients with persistent cytopenias. No patient treated with TREGZI has developed PTLD. Monitor for malignancies of donor origin and secondary malignancies. Contact Orca Bio at 1-877-290-6722 if any patient is diagnosed with a secondary malignancy or a malignancy of donor origin.

Transmission of Infectious Agents: Transmission of serious infectious or communicable disease or agents may occur with TREGZI treatment as it is derived from human donor blood and manufactured using animal-derived reagents. Risks of transmission of infectious agents may occur despite screening or testing of donors. Risks of transmission of serious infections include, but are not limited to, human immunodeficiency virus, human T cell lymphotropic virus (HTLV)-1 and -2, hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum, Trypanosoma cruzi, West Nile virus (WNV), cytomegalovirus, transmissible spongiform encephalopathy agents and vaccinia. Monitor patients for signs and symptoms of infections, perform tests for infectious agents and treat as clinically indicated.

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥ 20%) were mucositis, diarrhea, rash, viral infections, infections – pathogen unspecified, abdominal pain, vomiting, nausea, bacterial infections, hemorrhage, aGVHD, edema, and fungal infections.

The most common Grade 3-4 laboratory abnormalities (≥ 20%) are lymphocyte count decreased, platelet count decreased, leukocyte count decreased, neutrophil count decreased and hemoglobin decreased.

INDICATIONS AND USAGE

TREGZI is indicated for use in matched donor hematopoietic stem cell transplantation with myeloablative preparative regimen, for hematopoietic and immunologic reconstitution and to improve chronic graft-versus-host disease-free survival, in the treatment of adults with hematological malignancies.

Please see accompanying full Prescribing Information.

References:

  1. Broglie L, Xu K, Oloyede T, Chen M, Allbee-Johnson M. Current Uses and Outcomes of Cellular Therapy in the US, Summary Slides 2025. https://cibmtr.org/Files/Summary-Slides--Reports/2025-Summary-Slides-Final-for-WEB.pptx. Accessed June 18, 2026.
  2. Heinrichs J, David Bastian D, Veerapathran A, et al. Regulatory T-cell therapy for graft-versus-host disease. J Immunol Res Ther. 2016;1(1):1-14.
  3. Methotrexate Prescribing Information. Accord Healthcare, Inc; 2026.
  4. Perkins J, Field T, Kim J, et al. A randomized phase II trial comparing tacrolimus and mycophenolate mofetil to tacrolimus and methotrexate for acute graft-versus-host disease prophylaxis. Biol Blood Marrow Transplant. 2010;16(7):937-947.
  5. Luznik L, Pasquini MC, Logan B, et al. Randomized phase III BMT CTN trial of calcineurin inhibitor-free chronic graft-versus-host disease interventions in myeloablative hematopoietic cell transplantation for hematologic malignancies. J Clin Oncol. 2022;40(4):356-368.
  6. Luznik L, Pasquini MC, Logan B, et al. Randomized phase III BMT CTN trial of calcineurin inhibitor-free chronic graft-versus-host disease interventions in myeloablative hematopoietic cell transplantation for hematologic malignancies. J Clin Oncol. 2022;40(4):356-368, supplementary appendix.
  7. Gradone A, Bi X, Durugu S, et al. The heart of the matter: cardiac toxicity in allogenic stem cell transplant with post-transplant cyclophosphamide. Transplant Cell Ther. 2026;32(1):65-73. doi:10.1016/j.jtct.2025.09.009.