Pharmacists Help Guide Regimen Choice Between Flu/Cy/TBI and Flu/Bu2

In an interview with Pharmacy Times, Monica Sawiris, PharmD currently a PGY2 oncology pharmacy resident at Atrium Health Wake Forest Baptist in Winston-Salem, discussed findings from her presentation presented at the HOPA Annual Meeting 2025. She shared her research comparing 2 non-myeloablative conditioning regimens for allogeneic stem cell transplants (alloSCT): Flu/Bu2 (fludarabine [Fludara; Teva Pharmaceuticals] and busulfan [Myleran; GlaxoSmithKline Group) and Flu/Cy/TBI (fludarabine plus cyclophosphamide [Cytoxan; Amneal Pharmaceuticals, Inc] and total body irradiation)

Pharmacy Times: Can you discuss what you presented at HOPA 2025?

Monica Sawiris, PharmD: Yeah, so my research project is comparing 2 non-myeloablative conditioning regimens for an [alloSCT]. The reason why we're comparing both is because at Wake Forest, we use fludarabine and busulfan as our conditioning regimen, but we recently merged with Levine Cancer Institute, and they use fludarabine, cyclophosphamide, and total body irradiation as their conditioning regimen. So, when we're trying to harmonize the two institutions, we're trying to figure out if there are any differences in efficacy or toxicities in both regimens. So that way we can decide on one over the other.

Pharmacy Times: What did the study reveal about progression-free survival (PFS) between the Flu/Bu2 and Flu/Cy/TBI groups? Were there any trends that surprised you?

Sawiris: So, we've looked at [PFS] as well as non-relapse mortality. In terms of progression-free survival, the Kaplan-Meier curve was all meeting together—there was no difference. Specifically in non-relapse mortality, there was no difference as well. It wasn't as surprising, but we did see differences in toxicities. So, the efficacy was similar in both groups. The difference was in toxicities.

And we saw in the fludarabine-busulfan group more mucositis, which could be because of the busulfan. But we also use different graft-versus-host prophylaxis regimens. The majority of patients used the post-cyclophosphamide, tacrolimus, and mycophenolate, but some patients did use methotrexate in their GVHD prophylaxis, and that's where we saw a majority of the mucositis in that group.

And then in terms of the fludarabine, cyclophosphamide, and the TBI, we saw more renal toxicity—as well as the—there were like two more toxicities of infectious complications and febrile neutropenia.

Pharmacy Times: How did the incidence of acute and chronic graft-versus-host disease (GVHD) compare between the Flu/Bu2 and Flu/Cy/TBI groups? Did GVHD correlate with regimen intensity or toxicity?

Sawiris: So, for acute GVHD, we saw there were no statistical differences in both groups, but there was a higher percentage in the fludarabine, cyclophosphamide, and total body radiation group, which kind of has to do with the TBI use because we want to suppress their immune system more. But in terms of chronic GVHD, it was higher in the fludarabine-busulfan group, which was also suspected. But it was kind of unique, but there were no differences in those groups—it was just a higher percentage.

Pharmacy Times: Based on your findings, do you believe one regimen is preferable for certain patient populations or disease types?

Sawiris: Yeah, so the next step for this research project is it will be presented to the medical team at both Wake Forest and Levine Cancer to allow the two regimens to be an option, since there's no difference in efficacy. So, it’ll be based on toxicities and patient characteristics.

So for example, if a patient has chronic kidney disease, then we would utilize fludarabine-busulfan, because there was more renal toxicity in the fludarabine, cyclophosphamide, and TBI group. So it would be more based on patient characteristics to determine which one to use.

Pharmacy Times: Can you discuss the role of the pharmacist?

Sawiris: Whenever they determine a patient is eligible for an allogeneic stem cell transplant, the next question is: which conditioning regimen would be utilized? So as a pharmacist, I'll be reviewing patient past medical history, their labs, to determine if they're at a higher risk for either toxicities, and that way we can discuss with the medical team—on we have those two conditioning regimens, this would cause more mucositis, this would cause more renal toxicity. Based on patient profile, I would recommend like the flu-B, the flu-Bu for example. And that way it's more of a discussion based on patients. And then in terms of kinetics, we don't really do kinetics for busulfan nor for fludarabine, and so it would be more of just the standard dosing.