The study at ASH was trying to attempt if we are able to identify a cohort of patients that are low risk for relapse for which avoiding total body irradiation, which has been the standard of care as a conditioning regimen for transplant for acute lymphoblastic leukaemia, may allow us to still maintain excellent outcome and do not increase the risks for decreased outcomes.
Total body irradiation has been the standard of care for acute conditioning regimens for acute lymphoblastic leukaemia, however, it is associated with short- and long-term morbidities for younger patients as well as adult patients. Therefore, this trial was attempting to identify a subgroup of patients for whom we are able to change that conditioning regimen standard of care to be a non-TBI-based regimen.
What was the study design?
The study design included an observational arm and a phase II treatment arm. Basically, all of the patients who were coming to transplant who fulfilled the study eligibility criteria would undergo a testing of a baseline sample before going to transplant with a very sensitive technology called next general sequencing minimal residual disease assessment, to be able to identify if there is any residual leukaemia in their bone marrow or peripheral blood that we cannot see by microscope or by conventional methods for assessing minimal residual disease but we are still able to detect with very high sensitivity any hidden leukaemia cells.
Patients who we were not able to detect any residual disease by this very sensitive method were offered to participate in the phase II trial where they would receive an non-TBI-based conditioning regimen prior to allotransplant. The study was open in 45 North American centres and basically any trend for an extended amount of time from the years of 2018 through 2025. It enrolled 202 subjects, 51 subjects on the treatment arm, the phase II study, and 151 subjects on the observational arm.
What were the results of this study?
The primary analysis of the study showed that we achieved our event free survival, which was the two-year event free survival of 76.3% and the two-year overall survival of 82%, basically achieving our primary endpoint for this study. The primary conclusion of the study, that the overall survival and the event free survival in our treatment cohort were comparable to the published CIBMTR results in B-cell ALL where patients predominantly received TBI-based conditioning.
Our overall survival and event free survival in our phase II non-TBI arm for the NGS MRD negative B-ALL matched our hypothesis with a two-year event free survival of 76.3% and overall survival of 82% which is comparable to recent published data from the forum ‘Outcome for MRD negative patients receiving TBI’. Also, our treatment arm results compared favourably to the forum study, ‘Non-TBI-based conditioning regimen: two-year event free survival’, which were 58% event free survival and 75% overall survival.
Basically, our study in the short-term was able to show that we are able to spare certain patients who are at low risk for relapse from receiving a pre-transplant TBI conditioning regimen which means changing the standard of care at the current time and also not compromising the outcomes of those patients with changing the conditioning regimen from a TBI-based regimen as the standard of care to a non-TBI-based regimen.
What is the clinical significance of these results and what is next for this study?
Those results are very significant because it does have an impact on the current standard of care. The current standard of care, all of the patients who are diagnosed with ALL pre-transplant would receive a total body irradiation-based conditioning regimen. But based on the results of this study we may be able to dissect this further and save a portion of those patients who test pre-transplant NGS MRD negative the TBI conditioning and use a non-TBI-based conditioning. So this is really a standard of care changing study, this is number one.
The next step, we are planning an additional analysis which will compare the outcomes for a matched cohort from the CIBMTR controls and assess the impact of acute and chronic GVHD as well as prior immunotherapies on outcomes which will further give us a clearer picture on basically when can we change or [??] that regimen, what’s the impact of those different factors on regimen change preconditioning in bone marrow transplant.
Is there anything else you would like to add?
The most important thing I would add to the interview, really what’s happening in the transplant world today is completely different than what was happening in the past few years. It’s a rapidly progressing field where now we are able to improve the outcome, decrease the toxicity and basically have an overall favourable prognostic impact on different patients who are receiving transplant, especially in this study for acute lymphoblastic leukaemia.
