BMT Tandem Meetings | Ommited doses of post-transplant MTX with alternative agents as GvHD prophylaxis – a retrospective study

Andrew Lin and colleagues from Memorial Sloan Kettering Cancer Center, New York, NY, conducted a retrospective analysis of outcomes in patients who had varied quantities of mini-methotrexate (MTX) doses with a calcineurin inhibitors (CNI) following allogeneic transplant. The results were presented on February 21 at the 2018 BMT Tandem Meetings in Salt Lake City, UT.

The full dosing schedule for mini-MTX, graft-versus-host disease (GvHD) prophylaxis, is 4 doses given intravenously. This analysis reviewed GvHD and survival results for patients based on receipt of 1-3 or all 4 doses of MTX after transplant. In cases when fewer than 4 doses were given, alternate prophylaxis agents, such as corticosteroids or MMF were added to therapy.

Patients:

• N = 198 total patients
  • Omitted dose group = 35, median age = 48.9 years
  • Full dose group = 163, median age = 55.3 years

Key findings:

• Reasons for dose omission: mucositis, hyperbilirubinemia, pleural effusions
• Results at 36 months
  • Non-relapse mortality: omitted dose =36.4% vs full dose = 16.6%, P = 0.008
  • GvHD-free mortality: omitted dose = 20.6% vs full dose = 12.8%, P = 0.220
  • cGvHD: omitted dose = 15.7% vs full dose = 30.6%, P = 0.096
  • Overall survival: omitted dose = 37.4% vs full dose = 53.8%, P = 0.008
  • Relapse -free survival: omitted dose = 29.6% vs8%, P = 0.046

The findings of this study demonstrated that skipping doses of mini-MTX did not impact incidence of cGVHD, but relapse prior to cGVHD development was considered a competing risk and it led to adverse survival outcomes. Administering an alternative agent, MMF or corticosteroids may improve the increased risk of aGvHD.Key limitation of this study was the small number of patients receiving omitted doses of MTX.

Given the expectation of poor survival outcomes when methotrexate is omitted, it is crucial for medical teams to provide sufficient supportive care of toxicities, which will allow patients to receive a full four-dose schedule.