Cost Analysis Strengthens the Case for Orca-T in Allo-HCT

Orca-T, an investigational allogeneic T-cell immunotherapy, has shown potential to reduce chronic graft-vs-host disease (GVHD) prevalence and severity compared with traditional allogeneic hematopoietic cell transplant (allo-HCT).¹ Its efficacy was demonstrated in the phase 3 Precision-T trial (NCT04013685) vs standard transplant with tacrolimus and methotrexate as GVHD prophylaxis. But in addition to the direct benefit to patients, the novel transplant approach presents the opportunity to reduce the financial burden that GVHD prevention and treatment has on patients and health systems.²

“[Although] it is an investment upfront for institutions to provide this therapy, in the long term, if we’re able to reduce that risk of chronic GVHD, reduce that risk of rehospitalization, etc, then we can have cost savings on the backend,” said Rawan Faramand, MD, in an interview with Targeted Oncology.

Faramand, who is an associate member in the Department of Blood and Marrow Transplant and Cellular Immunotherapy at the Moffitt Cancer Center in Tampa, Florida, presented research on the cost-effectiveness of Orca-T vs standard GVHD prophylaxis at the European Marrow and Blood Transplantation Society Annual Meeting (EBMT), projecting a net monetary benefit of about $1.7 million based on the Precision-T outcomes, with meaningful cost savings maintained even with the newer post-transplant cyclophosphamide (PTCy) regimen.

In the interview, Faramand discussed the significance of the cost-effectiveness analysis on the modern transplant landscape in hematologic malignancies, the importance of addressing chronic GVHD rapidly, and other vital developments that were showcased at the EBMT conference.

Targeted Oncology: Could you give an overview of the financial burden that currently affects patients treated with allogeneic transplant associated with GVHD?

Rawan Faramand, MD: I had the opportunity to present the cost-effectiveness analysis of Orca-T in comparison to conventional GVHD prophylaxis with tacrolimus/methotrexate. As we’ve learned throughout the years, we’ve made significant advances in both the prevention and treatment of GVHD. However, the treatment for both acute and chronic GVHD is very costly to our patients.

Although we’ve seen a lot of clinical improvements in the way that we manage GVHD, now we’re seeing also the financial burden and financial toxicity of these medications. We know that the vast majority of patients with chronic GVHD will continue to be on immunosuppressive therapy. Only about one-third of patients are able to get off therapy, typically at a median of 5.5 years, so for many of our patients, it is a lifelong illness. Anything that we can do to both hopefully cure their disease—reduce the burden of GVHD—but also be cognizant of the financial burden to our patients, is very important.

What gives Orca-T the potential to address these cost-effectiveness issues?

Many of our advancements in the way that we’re managing both prevention and treatment of GVHD rely on pharmacologic agents, and many of them have been promising. The way that Orca-T is different is that this is using precision technology to control what we’re giving to the patients in terms of the graft. We’re relying on graft engineering in a very precise way, as opposed to pharmacological therapy.

The Precision-T clinical trial…was a phase 3 randomized clinical trial for patients receiving myeloablative conditioning for the diagnosis of acute leukemia or high-risk myelodysplastic syndrome. We saw a significant improvement in survival free of chronic GVHD, in comparison to the comparator arm, which was standard tacrolimus/methotrexate.

What we did is a 3-state model, taking into account patients who are alive and relapse free, patients who are alive and relapsed, and unfortunately, those patients who’ve died. Then we put in key inputs of what can potentially impact the cost for patients. We looked at hospitalization rates, the cost of infections, and treatment of acute and chronic GVHD among other factors. All of that is based on the US market, since this is where the clinical trial was conducted, so it doesn’t necessarily apply to a European audience.

For acute GVHD, we took into account a one-time treatment cost and that was based on what treatment patients received on the clinical trial. For chronic GVHD management, it was a monthly cost based on expected management looking at rates of chronic GVHD in the clinical trial. The majority of the analysis was conducted against tacrolimus/methotrexate, since that’s…where we had all the data from the clinical trial, but acknowledging that PTCy now is increasingly used in the myeloablative setting, we also did a secondary analysis comparing to PTCy.

What were the key findings of the study that you presented at EBMT?

In essence, we found that Orca-T because it does reduce that risk of chronic GVHD, showed a net monetary benefit of about $1.7 million in comparison to tacrolimus/methotrexate. We take into account the direct medical cost savings, and then we take into account quality-adjusted life-years (QALYs) in which Orca-T led to a gain of 4.34 QALYs. Lastly, looked at the willingness-to-pay threshold, which is about $150,000 in the US for oncology drugs, and that’s where we came up with the net monetary benefit of $1.7 million.

So, [although] it is an investment upfront for institutions to provide this therapy, in the long term, if we’re able to reduce that risk of chronic GVHD, reduce that risk of rehospitalization, etc, then we can have cost savings on the backend. When we compared it with PTCy, there was a net monetary benefit of about $621,000; less so than tacrolimus/methotrexate, because we expect a reduction in chronic GVHD of GVHD rates in the PTCy recipients, but still an overall net monetary benefit.

How might ongoing changes in GVHD prevention and management affect this calculation?

We don’t, unfortunately, have any randomized prospective data comparing with PTCy, which would be ideal. There [are] not randomized multicenter data looking at PTCy in the [myeloablative] setting, so that limits some of the data that we had to input into our analysis, because [those data are] not there. Therefore, we relied on data from BMT CTN 1301 [NCT02345850], which is a limitation since patients on the study received single-agent PTCy primarily with a bone marrow graft.

But to your point, the landscape of GVHD is certainly changing. There were some exciting presentations at EBMT looking at calcineurin-free inhibitor protocols that [Samer Al-Homsi, MD, MBA], for example, presented.³ We don’t know [how] in the future, with better GVHD prevention strategies, that could impact the financial burden to our patients. I think many of these trials are exciting, but they’re still early, so we’ll have to wait for those data to mature.

What are the broader effects that the cost of treatment for GVHD has on a health system in the US?

Any health system is going to be looking at the bottom line, because when you’re looking to make a big investment upfront, we want that investment to pay back. Here we see improvement in our primary end point, which is survival free of chronic GVHD. We know that GVHD management is expensive. Many of these patients end up in the requiring frequent hospital stays and clinic visits increasing health care utilization. Many times, because of the treatment of GVHD and being on immunosuppression, they have a higher risk of infections. So if we’re able to reduce all those secondary problems that we can see after transplant, a healthcare system will end up making more money or being net even in the end if we’re able to invest upfront in better therapies, which is similar what we’ve seen across the board for CAR [chimeric antigen receptor] T-cell therapies, which were also very expensive and there was a lot of hesitation when they came out, but a lot of the health outcomes analyses and financial analyses have shown that they are cost-effective if you have better treatments up front.

What do you think physicians should take away from this?

I think the Precision-T data speaks for itself. It’s a randomized phase 3 study which met its primary end point. As one of the investigators on the clinical trial, we were very encouraged by that data, particularly the very low rates of nonrelapse mortality, despite patients receiving intensive conditioning.

When we look at healthcare-related quality of life, which [Arpita Gandhi, MD, MS] also presented as an oral presentation at EBMT,⁴ it also showed improvement in the Orca-T recipients as well as improvement in the rates of rehospitalizations and ICU stays. Overall, from a patient standpoint, this is very effective therapy when we’re comparing with tacrolimus/methotrexate, and now we’re able to show that not only is this therapy effective, but even though it may be expensive in the beginning—and we don’t know what the price point will be, because the PDUFA [Prescription Drug User Fee Act] target date [for FDA approval of Orca-T] is going to be in July, so we’ll find out more then—but when we’ve tested it across different price points, we find that there is value and that net monetary benefit is high in those patients.

In this community of providers who treat GVHD, when we see these patients suffer with GVHD, we’re always looking for any therapy that can improve those rates of chronic moderate-to-severe GVHD.

Many of us, even outside of clinical trial, are combining chronic GVHD drugs, and that overall is very costly, because the of high monthly cost of these drugs. If you’re on 2 agents instead of 1, and you’re on that agent for a long period of time, then that only ends up adding more to the cost of these therapies lifelong. But of course, we want effective treatments. If that’s what’s in the best interest of the patients, that’s what we would do.

What other takeaways did you have from attending EBMT?

EBMT is, overall, a great conference. I love the focus on transplant and cellular immunotherapy, as compared to the [American Society of Hematology Annual Meeting], which can be quite large and covers broader topics. There have been exciting data presented, in particular for GVHD. To have a calcineurin [inhibitor]-free trial is really intriguing. I’m excited to see more about [those] data, and as the data mature, to learn more about that. The combination data with the axatilimab and ruxolitinib is exciting, as well as the axatilimab once-a-month dosing, because with any therapy that’s biweekly, from a patient point of view, they’re always trying to see if we can spread it out more. If it’s still safe and effective every 4 weeks, I think that’s something we as a transplant community would be really excited about.

Dr Gandhi, like I mentioned, presented that quality-of-life data, which was very exciting. [Amandeep Salhotra, MD] also presented data looking at Orca-T in comparison to PTCy.⁵ Of course, that’s retrospective, taking data from CIBMTR [the Center for International Blood and Marrow Transplant Research], because we don’t have [those] prospective data, but overall showed improvement in overall survival and relapse-free survival.

The main takeaway in terms of GHVD is trying to have more effective upfront therapies to prevent GVHD, but also deintensification of therapy. We’re trying to move towards lower doses of PTCy, for example, and the calcineurin [inhibitor]–free studies, so trying to have better effective therapies upfront that are also safer. [We are] trying to find ways where we can get patients off immune suppression quicker if we have more effective GVHD prevention strategies. I think in the treatment setting, it’s much more about combinations of therapies and sequencing of therapy.

REFERENCES

1. Meyer E, Salhotra A, Gandhi A, et al. Orca-T versus allogeneic hematopoietic stem cell transplantation (PRECISION-T): a multicenter, randomized phase 3 trial. Blood. Published online December 12, 2025. doi:10.1182/blood.2025031313

2. Cost-effectiveness of Orca-T vs allo-HCT with conventional GVHD prophylaxis for the treatment of advanced hematologic malignancies in the United States. Presented at: 2026 EBMT Annual Meeting; March 22-25, 2026; Madrid, Spain. OS12-02

3. Al-Homsi AS, Boisclair S, Cole K, et al. Post-transplant cyclophosphamide dose reduction within an entirely calcineurin and mTOR inhibitor-free GVHD prophylaxis regimen: interim results of the ABC phase I-IIb trial. Presented at: 2026 EBMT Annual Meeting; March 22-25, 2026; Madrid, Spain.OS12-07.

4. Gandhi A, Purdum A, Pavlova A, et al. Orca-T demonstrates favorable quality of life and healthcare resource use compared to standard alloHSCT plus TAC/MTX for GVHD prevention in randomized phase3 clinical trial (Precision-T). Presented at: 2026 EBMT Annual Meeting; March 22-25, 2026; Madrid, Spain.OS14-01.

5. Salhotra A, Tamari R, Oliai C, et al. Clinical outcomes in Orca-T and registry-based post-transplant cyclophosphamide patients: an observational comparison. Presented at: 2026 EBMT Annual Meeting; March 22-25, 2026; Madrid, Spain. OS14-02.