The 2022 Tandem Meetings | Optimizing myeloablative conditioning regimens in older patients receiving alloHSCT
Uday Popat, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, gives an update on a Phase II trial evaluating different doses of busulfan and thiotepa to optimize conditioning regimens in older allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients. Overall, it was found that the outcomes of patients treated with lower doses of busulfan were similar to those of patients treated with higher busulfan doses. This interview took place at the Transplantation & Cellular Therapy (TCT) Meetings of ASTCT™ and CIBMTR® 2022 in Salt Lake City, Utah.
Transcript (edited for clarity)
As I mentioned earlier, our focus has always been to develop a better tolerated myeloablative regimen, preparatory regimen for transplant for older patients. And post-transplant Cy was the first step in that direction. Next, what we found was thiotepa when added to busulfan and fludarabine does allow for engraftment of haploidentical donor. Second, we saw that relapse rate was low in earlier studies...
As I mentioned earlier, our focus has always been to develop a better tolerated myeloablative regimen, preparatory regimen for transplant for older patients. And post-transplant Cy was the first step in that direction. Next, what we found was thiotepa when added to busulfan and fludarabine does allow for engraftment of haploidentical donor. Second, we saw that relapse rate was low in earlier studies. However, this was also associated with higher non-relapse mortality. So our goal was, could we optimize the dose of busulfan and, or thiotepa to reduce non-relapse mortality while maintaining the reduced relapse rate. And so we, in our ongoing trial, we started two cohorts. And so in one cohort, we reduced the dose of thiotepa from 5 milligram per kilo, to 2.5 milligram per kilo, leaving everything as is. Busulfan was given in myeloablative doses, at the area under the curve, 20,000. In the second cohort, what we did was we actually left the thiotepa dose at five milligrams, however, increased the busulfan dose to 20,000 or reduced the busulfan dose to 16,000. So in one cohort, we reduce the busulfan. In the other cohort, we reduce the thiotepa dose.
We are presenting the results of both cohorts over here. The bottom line is the outcomes were similar. However, when we decided to enroll patients, we chose to enroll more older patients and patients with comorbidity on lower busulfan or 16,000 busulfan with five milligram per kilo of thiotepa. This resulted in similar outcomes to the higher dose. In fact, what was interesting, what we found was the full donor chimerism was, a hundred percent donor chimerism rate, was significantly higher in the higher thiotepa dose group and lower busulfan group. So for all these reasons, even though the results are similar, but because they were obtained in older age group and patients with comorbidity with lower dose of busulfan and five milligram per kilo of thiotepa, that is the regimen we are taking forward in our future studies.
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