EHA 2024 | Low-intensity venetoclax-based preconditioning followed by sequential alloSCT for R/R AML or HR-MDS

So again, this was a retrospective single-center analysis of our relapsed/refractory patient cohort.

These were 25 patients who have been previously treated with a median of one therapy line, whereas 44% of those 25 patients had received two or more prior therapy lines. Importantly, the majority of those patients had relapsed/refractory acute myeloid leukemia, while lower numbers of patients had high-risk MDS. Importantly, more than half of patients (52%) were exposed to prior venetoclax and HMA. So this is an important subgroup of those patients. Half of those patients had adverse risk cytogenetics, and 36% had TP53-mutated disease. So really a hard cohort of patients to treat.

So the idea of our approach was to initiate the combined salvage regimen and then move those patients directly to an allo transplant without waiting for heme recovery and a conventional response. So basically, those preconditioning regimens consisted of venetoclax, low-dose cytarabine, and actinomycin D with the addition of a hypomethylating agent, so a quadruplet, and 44% of our patients had received an additional fifth drug, which was gilteritinib, cladribine, trametinib, navitoclax. So basically a multi-drug combination, which then with a median of one washout day, so only after one day, those patients directly proceeded to a conventional conditioning and a stem cell infusion.

So this sequential approach resulted in a 90% CR plus CRP rate. Again, 90% achieved a complete remission or a complete remission within incomplete platelet recovery. The majority of those responses were MRD-negative, and again, in a very difficult group of patients to treat, the median overall survival after this approach in this cohort was nine months, but the 24-month overall survival was around 40%. So again, offering a possibility for those heavily pretreated patients who had been already exposed to venetoclax plus HMA and having poor risk cytogenetics and molecular profile. Again, almost all patients had been classified to ELN 2022 adverse risk group.

So this has also become one of the standards of cares at our institution, performing a sequential allogeneic stem cell transplantation for those relapsed/refractory patients with non-intensive [preconditioining]. Again, we’re not using intensive chemotherapy here, no high-dose cytarabine or anthracyclines. So this is basically based on a low-intensity targeted therapy-based approach.