Orca-T Graft Improves Outcomes in Myelofibrosis Following Allogeneic Stem Cell Transplant

Arpita Gandhi, MD, discusses a subgroup analysis of patients with myelofibrosis who received Orca-T and how this type of therapy could be a game-changer for this patient population.

Treatment with Orca-T following myeloablative allogeneic stem cell transplantation led to high rates of efficacy and tolerability in patients with myelofibrosis enrolled on the single-center phase 2 trial (NCT04013685) and a multicenter phase 1b trial (NCT01660607).1

The 3-arm study features patients who are in remission (arm 1); those who are in remission but may have minimal residual disease, or have not achieved remission (arm 2); and those with high-risk or very high-risk myelodysplastic syndrome and myelofibrosis (arm 3).

The data, which were presented during the 2021 ASH Annual Meeting, were part of a subgroup analysis of 7 patients with myelofibrosis who were on the 2 studies for Orca-T. Patients had a Dynamic International Prognostic Scoring System of int-1 (n = 1) or int-2 or higher-risk myelofibrosis (n = 6). Investigators compared the 7 patients on Orca-T with 6 patients with myelofibrosis who received standard allogeneic stem cell transplant at Stanford University Medical Center between 2017 and 2021.

Results showed that Orca-T graft was well tolerated, led to early regression of marrow fibrosis by day +100 in all Orca-T–treated patients with myelofibrosis and so far there was no acute GVHD.

In an interview with OncLive®, Arpita Gandhi, MD, an assistant professor in the Division of Hematology Oncology at Oregon Health & Science University (OHSU) and lead study author, discussed the subgroup analysis of patients with myelofibrosis who received Orca-T and how this type of therapy could be a game-changer for this patient population.

OncLive®: Please discuss the data from the subgroup analysis on Orca-T activity, which specifically pulls out patients with myelofibrosis, a population with an unmet need to improve outcomes.

Gandhi: Myelofibrosis is usually excluded from lots of clinical trials, especially in allogeneic transplantation trials when looking at graft-vs-host disease [GVHD] prevention. These patients generally do poorly with stem cell transplantation. Orca-T, in the multicenter trial, included [patients with] myelofibrosis and we have an abstract that reviewed myelofibrosis outcomes on this patient population on this trial.

While the numbers are small, it's impressive to note how well Orca-T graft was tolerated by patients with myelofibrosis. [It is possible that using Orca-T without methotrexate lessens acute GVHD], and likely allows for a reduced inflammatory state in these patients with myelofibrosis, which may have resulted in the overall tolerability. It is an unmet need in the field of allogeneic stem cell transplantation for myelofibrosis.

Was the activity in the myelofibrosis subset at all different than the activity that we saw in the overall study population?

The number of patients on this abstract is too small to make such comparisons. But, it was very important to report this subgroup analysis because, usually, these patients are excluded from trials with other hematologic malignancies. There was a nice abstract at an ASH meeting few years ago to report experiences from Memorial Sloan Kettering Cancer Center with complete T-cell depletion in less than 20 patients with myelofibrosis. I am not aware of any other retrospective or prospective graft manipulation trial for GVHD prevention in myelofibrosis.

This is a valuable observation since a relatively rare disease group is evaluated in one of the cohorts of a multicenter trial, showing that patients with myelofibrosis can get a myeloablative conditioning regimen, when indicated, may have reduced GVHD, have regression of their marrow fibrosis, and achieve what seems to be an acceptable immune reconstitution. This is impressive for patients with myelofibrosis, because they are usually transfusion dependent or at increased risk of infections in the posttransplant period, ultimately resulting in increased mortality. I would say this is still an early observation and we need more data to make definitive conclusions.

You mentioned that many patients with myelofibrosis are typically excluded from certain transplant clinical trials. Can you expand further on that and the challenges with enrolling this type of population on studies?

Patients with myelofibrosis carry high risk for non-relapse mortality, which is unique to its disease-related features and it becomes difficult to put them on a trial with acute leukemias with a different non-relapse mortality profile. Myelofibrosis was included in the original early-phase studies with Orca-T graft and it remains on this multicenter trial. When you have a relatively rare disease like myelofibrosis, the data come from large retrospective studies or small prospective studies, and is often excluded from large trials with goals to reduce GVHD. I hope we will have more data from this multicenter trial to potentially consider a dedicated trial for myelofibrosis.

Is there anything else about this abstract in particular that you would like to mention?

Patients with myelofibrosis treated with Orca-T graft had presence of minimal residual disease [MRD] at the time of transplant and they were MRD negative on their posttransplant evaluation.

Reference

  1. Gandhi A, Moroz A, Muffly L, et al. Outcomes for myelofibrosis patients following myeloablative allogeneic stem cell transplantation using the Orca-T graft from HLA-matched related and unrelated donors. Presented at: 2021 ASH Annual Meeting and Exposition; December 11-14, 2021; Atlanta, GA. Abstract 1819.