PTCy and short-term everolimus as GvHD prophylaxis: Results from the phase II OCTET-EVER trial

The phase II OCTET-EVER trial assessed the safety and efficacy of post-transplant cyclophosphamide (PTCy) and short-term everolimus as graft-versus-host disease (GvHD) prophylaxis following a reduced intensity conditioning (RIC) peripheral blood allogeneic hematopoietic stem cell transplantation (allo-HSCT) from a matched donor in 19 adult patients with relapsed/refractory (R/R) lymphoma or multiple myeloma.¹ The final results from this trial were published in the European Journal of Haematology by Richardson et al.¹

The incidence of acute GvHD was 53%, with no cases of Grade III or IV acute GvHD observed, while 26% of patients developed chronic GvHD, graded as mild and moderate in 16% and 10% of patients, respectively; only patients with moderate chronic GvHD continued systemic immunosuppression.

Non-relapse mortality was low at 11%, 11%, and 16%, at 1, 2, and 4 years, respectively.

The study demonstrated favorable long-term outcomes, with a 4-year overall survival (OS) rate and GvHD-free relapse-free survival (GRFS) rate of 62% and 33%, respectively, highlighting the potential of PTCy plus everolimus to improve survival outcomes post-transplant.

Infectious complications were low, and hematological toxicities were as expected, indicating that the combination regimen of PTCy and everolimus was well tolerated, with no new toxicity signals observed.

These findings suggest that incorporating everolimus into standard GvHD prophylaxis regimens with PTCy could enhance patient outcomes in clinical practice, providing a promising alternative to traditional calcineurin inhibitor-based approaches for patients with R/R lymphoma or multiple myeloma following RIC peripheral blood allo-HSCT from a matched donor.