Sagar Patel, MD, discusses the utility of the Orca-T platform in patients with hematologic malignancies, highlighting the platform's safety.

Dr Patel on the Utility of Orca-T in Hematologic Malignancies

Sagar S. Patel, MD, director, Communications and Media Relationships, medical oncologist, Division of Hematology, University of Utah Huntsman Cancer Institute, discusses the utility of the Orca-T platform in patients with hematologic malignancies such as myelodysplastic syndromes (MDS), highlighting the platform’s safety.

Orca-T is a cell therapy biologic characterized by its precision. It comprises stem and immune cells sourced from allogeneic donors and harnesses highly purified, polyclonal donor regulatory T cells to manage alloreactive immune reactions. Within the framework of a phase 1b investigation, Orca-T underwent assessment in patients diagnosed with MDS. Patel begins by stating that the findings from this study encompass several key aspects. Firstly, in early-phase studies involving cellular therapy products, it is crucial to demonstrate the feasibility of timely product delivery, given the inherent manufacturing step, Patel says, noting that this was observed in the study. Secondly, the 1-year disease-free survival rate with Orca-T was notably high, at 94%. Moreover, at this juncture, none of the patients experienced severe acute graft-versus-host disease (GVHD), and moderate-to-severe chronic GVHD occurred in only 2 patients, he notes.

Furthermore, addressing concerns regarding toxicity, the non-relapse mortality rate was 0% at 12 months, indicating a highly favorable response in the high-risk MDS patient population treated with the Orca-T platform, Patel expands. Generally, the therapy did not pose an increased risk of GVHD; Orca-T was associated with a lower incidence of GVHD compared with conventional allogeneic stem cell transplant, he elucidates. Additionally, the end point of non-relapse mortality encompasses all non–disease-related adverse effects, none of which were observed in this context, Patel relays.

Thus, the Orca-T platform appears to offer an effective means of administering intensive allogeneic stem cell transplant with reduced toxicity, he reports. This is particularly beneficial for older patients with comorbidities, indicating a promising avenue for improving treatment outcomes in this patient population, Patel concludes.

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Sagar Patel, MD, director of Communications and Media Relationships for the Division of Hematology, University of Utah, Huntsman Cancer Institute, discusses how the timing of autologous stem cell transplant (ASCT) can affect outcomes in those with myelofibrosis, including the risk of patients developing post-transplant complications.

ASCT is often an effective, potentially curative approach for the treatment of patients with myelofibrosis. However, many patients will experience post-ASCT complications such as splenomegaly, cytopenia, infection, and a higher risk of leukemic transformation. These adverse effects (AEs) are all associated with higher mortality.

The optimal timing for ASCT has been more clearly elucidated in tumor types such as acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS), according to Patel. For example, patients with AML or high-risk MDS can experience disease recurrence if there is a substantial delay in ASCT administration, Patel notes. Accordingly, these patients should undergo ASCT as soon as they have achieved complete remission, he says. 

However, the identification of patients who would benefit from early vs delayed transplantation strategies is not well understood in myeloproliferative neoplasms like myelofibrosis, Patel adds. Moreover, the timing of ASCT in myelofibrosis often depends on the availability of potential donors, as well as the patient’s response to first- or second-line therapeutics, Patel states. These agents are often utilized to potentially reduce future post-ASCT complications and improve other AEs, he explains.

The JAK inhibitor ruxolitinib (Jakafi) is one such agent and has been increasingly utilized in this space. Although ruxolitinib is known to improve spleen-related symptoms and quality of life in patients with myelofibrosis when administered perioperatively, it is not curative. Accordingly, patients who initially receive these treatments do not typically experience complete remission, and still require subsequent ASCT, Patel concludes. 

Sagar Patel, MD, discusses how the timing of autologous stem cell transplant  can affect outcomes in those with myelofibrosis, including the risk of patients developing post-transplant complications.

Dr Patel on How the Timing of ASCT Affects Post-Transplant Complications in Myelofibrosis

Sagar Patel, MD, director of Communications and Media Relationships for the Division of Hematology, University of Utah, Huntsman Cancer Institute, discusses complications following allogeneic stem cell transplant (ASCT) that can occur in patients with myelofibrosis.

Myelofibrosis is a myeloproliferative neoplasm that is often only curable with ASCT. However, due to some of the unique aspects of the myelofibrosis, patients can encounter several complications stemming from ASCT.

These unique aspects of the disease can include splenomegaly, which many patients with myelofibrosis present with at diagnosis. In patients with splenomegaly, the spleen acts like a sponge, and during an ASCT, stem cells are absorbed by the spleen, rather than the bone marrow, Patel explains.

Moreover, the bone marrow itself becomes fibrotic in patients with myelofibrosis, leading to a less hospitable environment for the stem cells to take hold during ASCT and potential issues with delayed engraftment, Patel continues. When patients experience delayed engraftment as a post-ASCT complication, this can cause several issues, including cytopenia, which would require patients to receive blood transfusions for a period of time, Patel adds. Following ASCT, patients are also at high risk for infections since they will be neutropenic for an extended duration, and those factors are associated with a higher mortality, Patel emphasizes.

Due to the higher rates of mortality in patients that present with these post-ASCT complications, the first 30 days following transplant are particularly critical, Patel explains. Compared with other hematologic malignancies, patients with myelofibrosis can experience a slower engraftment, which leads to these persistent challenges, Patel concludes.

Sagar Patel, MD, discusses complications following allogeneic stem cell transplant that can occur in patients with myelofibrosis.

Sagar Patel, MD

Articles

Dr Patel on the Utility of Orca-T in Hematologic Malignancies

Dr Patel on How the Timing of ASCT Affects Post-Transplant Complications in Myelofibrosis

Dr. Patel on Post-ASCT Complications in Myelofibrosis