ASH 2024 | A Phase II adaptive study of dasatinib and inotuzumab-based induction for newly diagnosed Ph+ ALL
Anand Patel, MD, University of Chicago Medical Center, Chicago, IL, comments on the interim results of a Phase II study investigating a dasatinib and inotuzumab ozogamicin-based regimen for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).
Dr Patel highlights that the study showed encouraging results, partly by utilizing an adaptive strategy, meaning that patients who did not achieve complete molecular remission (CMR) by cycle three were treated with ponatinib to deepen response. A signal for veno-occlusive disease (VOD) was initially observed, but this was successfully rectified by adjusting the dosing regimen. This interview took place at the 66th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript (AI-generated)
So this is a Phase II investigator-initiated study where we looked at induction for newly diagnosed Ph-positive ALL utilizing a dasatinib plus inotuzumab-based regimen. Initially, our induction period consisted of two cycles of dasatinib plus inotuzumab. So we enrolled seven patients on that part. And our primary endpoint was achieving a major molecular remission or deeper...
So this is a Phase II investigator-initiated study where we looked at induction for newly diagnosed Ph-positive ALL utilizing a dasatinib plus inotuzumab-based regimen. Initially, our induction period consisted of two cycles of dasatinib plus inotuzumab. So we enrolled seven patients on that part. And our primary endpoint was achieving a major molecular remission or deeper. And that was after two cycles of therapy, which is when we assessed that. What we found was for the first seven patients enrolled, all seven met that primary endpoint. However, we did see a signal of veno-occlusive disease, or VOD. So two of our first seven patients developed veno-occlusive disease. The reported rate of VOD with inotuzumab historically has been around 10% or so. So with that in mind, we paused the study, we amended the protocol, and we ultimately split the dosing of dasatinib and inotuzumab. So for the subsequent patients that have been enrolled, 12 up until this point, we gave dasatinib plus steroids for cycle one of therapy and inotuzumab monotherapy for cycle two. Our primary endpoint remained the same, which is MMR or better at the end of two cycles, and that has been achieved in nine of 12 patients so far.
This is also an adaptive study, meaning for patients who did not achieve a complete molecular remission, for cycle three and onwards, they were transitioned to ponatinib, a third-generation TKI. And every patient treated on study so far has achieved MRD negativity either by NGS to a sensitivity of 10 to the negative six or a CMR based on BCR-ABL PCR at the end of cycle three.
So we found this to be a very promising regimen. It seems like you don’t need to give a whole lot of antibody-based therapy to achieve a deep remission. And I think the adaptive nature of our protocol allows for switching someone’s TKI if you’re finding an inadequate response and being able to deepen that response and get the CMRs that we’re looking for that we know translate with long-term survival. The initial toxicity signal of VOD has not been seen at all since we’ve separated the two agents. So of all 12 patients that have been treated with this updated dosing regimen, we have not seen any evidence of VOD.
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Disclosures
Sumitomo: Research Funding; Bristol Myers Squibb: Honoraria; Sobi: Honoraria; AbbVie: Honoraria; Pfizer: Research Funding; Kronos Bio: Research Funding.
