Leonard commented, “I’ve heard about some pretty impressive responses, but I’ve also heard of some that were relatively short-lived, so it sounds like there is more work to do.”Phase I/II study of venetoclax (Venclexta) with low-dose cytarabine in treatment-naïve, elderly patients with AML unfit for intensive chemotherapy: 1-year outcomes (Abstract 890)
Long-term outcomes of this combination, including 1-year OS data and biomarker analyses will demonstrate the safety and preliminary efficacy of the combination, which was granted a breakthrough therapy designation by the FDA in July 2017 (NCT02287233). The agency’s decision was based on prior findings of this study presented at the 2017 European Hematology Association Annual Congress. These showed that the ORR was 61% with a CR rate of 21%, a CR with incomplete blood count recovery rate of 33%, and a partial remission rate of 7%.
“It looks like the addition of venetoclax to that background of low-intensity chemotherapy dramatically increases the response rate,” said Perl. “What is interesting about this abstract is not really the response rates—which you can do by adding more agents to low-dose cytarabine, but the durability of the response is what is much more important. There have been many drugs added to low-dose cytarabine that have had better responses, but no improvement in OS. This looks very promising because the 1-year survivals look very good.”Preliminary results from a phase I study of gilteritinib in combination with induction and consolidation chemotherapy in subjects with newly diagnosed AML (Abstract 722)
Gilteritinib, a highly-selective oral FLT3/AXL inhibitor was investigated in patients with newly diagnosed AML in this open-label, dose-escalation and dose-expansion phase I study (NCT02236013). The safety and clinical activity of the agent was explored when combined with frontline 7+3 induction and high-dose cytarabine consolidation therapy, and when administered as single-agent maintenance therapy in subjects aged ≥18 years with newly diagnosed AML.
“This has substantial single-agent activity in relapsed/refractory patients added to 7+3 therapy, and this is the first time the data with that drug had been presented in a combination regimen,” Perl explained. “As you can see, we are still working out the optimal dosing, but it seems like we can go to the same doses that were active in single-agent therapy, which seems to be quite tolerable and also the response rates are really quite high. There is not enough follow-up on this study to say how well this is working in the long run, but there are median survivals of about 1 year on this study [in patients] who were treated and the response rates were more than 90%.”Low relapse rate in younger patients ≤ 60 years old with newly diagnosed FLT3-mutated AML treated with crenolanib and cytarabine/anthracycline chemotherapy (Abstract 566)
Crenolanib is a potent type I FLT3 specific inhibitor, which can be safely administered at maximal doses in combination with 7+3 induction and high-dose cytarabine consolidation. Investigators will report the CR and relapse rates of patients younger than 60 years old with FLT3
-mutated AML who were treated with crenolanib plus standard induction chemotherapy. Results will be presented from 29 patients on the study.
“What you’re seeing again here is longer follow-up,” Perl said. “We don’t have a lot more information on response rates, but they are very high in frontline therapy. The big problem in particularly FLT3
mutant AML is relapse. This is very encouraging for early data.”Preliminary results of a phase I study of flotetuzumab, a CD123 x CD3 Bispecific Dart protein, in patients with relapsed/refractory AML and myelodysplastic syndrome (MDS; Abstract 637)
In a phase I trial, flotetuzumab (MGD006/S80880), a novel T-cell redirecting bispecific DART protein is being explored in patients with relapsed/refractory AML and MDS. Results will include the safety profile, MTD and schedule, and preliminary antileukemic activity of flotetuzumab.
“They did see cytokine release syndrome (CRS) and they did also see responses, so they basically looked like they found a manageable way to give immunotherapy with a single agent here for relapsed/refractory patients, and that is very encouraging,” Perl explained. “It is a very small study in determining what the optimal dose is, and the follow-up is still limited but this is encouraging. Again, this is not the only drug in this realm.”Role of allogeneic reduced intensity conditioning stem cell transplantation (RIC-SCT) in older patients with acute myeloid leukemia (AML): analysis of the ALFA-1200 study (Abstract 466)
Patients with AML who have intermediate- or adverse-risk genetics are candidates for allogeneic SCT in first complete remission. However, only a small subset of them undergoes SCT due to age, comorbidities, poor tolerance of prior therapy, inability to achieve CR, or early relapse. This study examines the benefit of RIC-SCT in older patients.