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Sagar S. Patel, MD, discusses data from a retrospective analysis of Orca-T and PTCy for hematologic malignancies and its implications for the field.
A retrospective analysis comparing Orca-T vs post-transplant cyclophosphamide (PTCy) following allogeneic hematopoietic stem cell transplant (alloHSCT), demonstrated promising efficacy and safety data for Orca-T in patients with hematologic malignancies, according to Sagar S. Patel, MD.1
Data from the analysis, which were presented at the
“[Orca-T] is going to be a viable treatment option that will add to the toolbox and ultimately enable [treatment selection] on a personalized level in which patients are appropriate for 1 regimen or another,” Patel said in an interview with OncLive®.
In the interview, Patel discussed the study, its results, and how he sees Orca-T stacking up against PTCy in clinical practice.
Sagar S. Patel, MD, is an associate professor of internal medicine in the Division of Hematology & Hematologic Malignancies at the University of Utah Huntsman Cancer Institute in Salt Lake City.
Patel: Orca-T is an investigational precision cell therapy platform for allogeneic stem cell transplants. At its core, it utilizes a] proprietary cell separation technique to better optimize the graft, ultimately improving the graft-vs-leukemia effect [and simultaneously] reducing GVHD. This [therapy] has been through phase 1 [trials] all the way up to a phase 3 clinical trial.
Orca-T vs PTCy for Hematologic Malignancies: Take-Home Points
As long as we’ve been conducting allogeneic stem cell transplants, we’ve had to deal with GVHD, both in the acute and chronic forms, as a significant limitation to the success of [transplants]. [Orca-T] is notable for patients who may have more comorbidities, older age, or general frailty who have a harder time tolerating the transplant and its associated complications. Orca-T is positioned to help reduce the rates of GVHD, as well as other complications indirectly tied [to GVHD]. Ultimately, this may have a positive effect on survival outcomes.
The phase 1b trial with Orca-T enrolled patients who had AML or MDS. We saw an excellent safety profile and low rates of GVHD. Now the question is: How does [Orca-T] compare with other potential approaches to reduce GVHD? One way [to answer this question] was to perform a registry-based retrospective analysis evaluating patients who received PTCy, which came about through the CIBMTR registry. [The CIBMTR registry] is the most robust resource for [these data]. [When conducting this] head-to-head comparison [of clinical trials], the goal was to investigate the typical high-yield outcomes of survival, GVHD, and RFS.
PTCy utilization has increased after the [readout of the] phase 3 BMT CTN 1703 study [NCT03959241], which predominantly evaluated [PTCy] in the reduced intensity-conditioning [RIC] context. However, many hematologists are extrapolating [PTCy] to myeloablative settings and using the treatment irrespective of underlying donor type; we have seen good [transplant complication] reductions [with this approach], including [reductions in] chronic GVHD [cGVHD].
However, PTCy is additional chemotherapy, so there are limitations in the form of organ toxicities that come with that additional treatment. Some of [the toxicities we focus on are] cardiac in origin, especially in patients with underlying, pre-existing cardiac issues, where receiving a full dose of PTCy may be problematic. In addition, there is potential for an increased risk of infection given the additional immunosuppressant [of PTCy]. [This context is where] an Orca-T platform, which uses single-agent GVHD prophylaxis with tacrolimus [Prograf], provides a benefit in reducing GVHD without compromising infection or relapse.
The [study investigators] tried to match [these populations] as much as possible, given the limitations that are inherent without this [analysis] being a prospective study. By cross-applying and evaluating the outcomes for these patients, we saw that the cumulative incidence of 1-year moderate-to severe-cGVHD was lower in the PTCy group, [although] the combined composite end point of cGVHD [incidence] and RFS was not significantly different [between the groups]. The patients who received Orca-T, in comparison with those who received PTCy, experienced increased OS, increased RFS, and decreased NRM rates.
This [study] helps address a data gap. We have prospective clinical trials, which primarily used control arms with tacrolimus and methotrexate as typical GVHD prophylaxis agents. Now that we are seeing increased use of PTCy [in patients with hematologic malignancies], this [retrospective analysis] helps address the question: How would [PTCy] compare in that setting?
One of interesting findings from the study was that there was an increased magnitude of efficcy favoring Orca-T in patients who were older than 50 years of age. That reflects the fact that PTCy may have upper limits regarding long- and short- term AEs that are more notable in an older patient population. This is relevant because we’ve been more successful in offering [transplants] to older patients than ever before. It’s not uncommon for us to do an allogeneic transplant even in patients who are 70 years of age. [Thus], we need to consider the full spectrum of age, as well as performance status, comorbidities, and frailty. It’s nice to offer a platform that’s well tolerated and does not compromise on long-term effects.
