Preventative treatment for GvHD in patients requiring haploidentical peripheral blood stem cell transplant: Preliminary findings from the phase II ANZHIT-1 study

In patients who need a stem cell transplant but do not have a human leukocyte antigen (HLA) matched related or unrelated donor, a haploidentical donor transplantation can be considered. Complications such as graft-versus-host disease (GvHD) due to haploidentical hematopoietic stem cell transplant (haplo-HSCT), have recently been overcome with the successful use of posttransplant cyclophosphamide (PTCy), making it increasingly popular. However, hitherto studies of haplo-HSCT using PTCy have been retrospective with multiple different regimes and cell sources, limiting the interpretation of data.

During the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, John Moore, St Vincent’s Hospital Sydney, AU, presented the preliminary results of a prospective multicenter cohort study (ANZHIT-1; ACTRN12617000151336) that assessed the use of PTCy in patients who had received a predefined conditioning regimen and were undergoing haplo-HSCT ¹.

Study design

• A phase II, prospective multicenter cohort study conducted in six Australian centers, stratified 78 patients into two conditioning regimens: reduced intensity conditioning (RIC; n = 46), and myeloablative regimen (MAC; n = 32). See details in Figure 1
• The primary endpoints were disease-free and overall survival at 1 year, while the secondary endpoints were engraftment, cumulative incidence of relapse, transplant-related mortality (TRM), and rates of chronic and acute GvHD
• Patients with a hematopoietic cell transplantation comorbidity index (HCT-CI) > 3 or age > 50 were advised to be on the RIC regimen

Figure 1. RIC and MAC regimens¹

CNI, calcineurin inhibitor; d, day; GvHD, graft-versus-host disease; MAC, myeloablative conditioning; MMF, mycophenolate mofetil; PTCy, posttransplant cyclophosphamide; RIC, reduced intensity conditioning; TBI, total body irradiation; TDS, thrice daily.

Results

Patient baseline characteristics

• A total of 78 patients were included in the study with a median follow-up of 404.5 days (28–1,259)
• Patients receiving MAC were younger and more likely to have ALL as diagnosis. See Table 1 for further details

Table 1. Patient baseline characteristics¹

Efficacy

• The overall survival rate at 1 year was similar between MAC and RIC patients (74.1% versus 77.8%). See Table 2 for further details.

Safety

• Acute GvHD Grade II–IV rates were high in the RIC arm, while only one patient in the MAC group developed acute Grade III–IV GvHD. Chronic GvHD at 1 year occurred in a high proportion of patients in both groups; however, most were mild to moderate
• TRM at 100 days was low in both groups, showing good tolerability of both regimens. TRM at 1 year increased to 18.8% in MAC patients while it was only 8.7% in RIC patients. Causes for TRM included infection (n = 5), GvHD (n = 3), and veno-occlusive disease (VOD), respiratory failure, and multi-organ failure in one patient each. One case of VOD in the MAC arm was fatal
• Relapse was the most common cause of mortality in RIC treated patients compared with MAC treated patients

Table 2. Primary and secondary outcomes¹

Conclusion

The study shows encouraging overall survival rates in patients at 1 year irrespective of conditioning regimen. However, early relapse in RIC patients is a concern, while TRM and toxicity profile were significantly higher in patients who received MAC. GvHD rates in both groups are high but majority are mild to moderate acute or chronic GvHD. While relapse seemed to be very well controlled in the MAC arm, a longer follow-up is required to assess relapse rates in both groups. The authors perceived a need for further refinement of the conditioning and GvHD prophylaxis regimen, which they have incorporated in their follow-up phase II multicenter (Australia and New Zealand) ANZHIT-2 study.