613. Acute Myeloid Leukemia: Novel Therapies and Treatment Approaches
David A. Sallman, Adam S. Asch, Suman Kambhampati, et al.
Authors Conclusion from the Abstract: Magrolimab is a novel immunotherapy and LSC-targeting agent that blocks a key macrophage checkpoint. Magrolimab+AZA is well tolerated with no immune-related AEs observed in relation to magrolimab. On-target anemia is mitigated by a priming/maintenance dose strategy. Efficacy is seen in both TP53-mutant and wild-type AML patients. While sample size and follow-up are limited, efficacy is particularly encouraging in TP53-mutant AML with a 71% response rate, 48% CR rate, and median OS of 12.9 months. Expansion cohorts in AML are ongoing (NCT03248479) and a phase 3 trial evaluating magrolimab+AZA in untreated TP53-mutant AML patients is planned. Additional patients, follow-up, and correlative studies will be reported at the time of presentation.
Ibrahim Aldoss, Geoffrey L Uy, Norbert Vey, et al.
Authors Conclusion from the Abstract: FLZ demonstrated encouraging activity in pts with PIF/ER AML, a population with poor prognosis and high unmet medical need, with 42.1% achieving CRR and over half of those receiving a stem cell transplant. Treatment is tolerable with a minimum 8 day inpatient treatment. The study is currently enrolling patients [NCT02152956]
Curtis Lachowiez, Marina Konopleva, Tapan M. Kadia, et al.
Authors Conclusion from the Abstract: The addition of VEN to FLAG-IDA demonstrated robust efficacy across AML subgroups with an acceptable safety profile, an ORR of 84%, and 76% of subjects achieving a CRc (ND: 89%, R/R: 66%). FLAG-IDA-VEN resulted in deep responses as indicated by MRD- CRs in 83% of patients achieving a CR (ND: 96%, R/R: 70%). FLAG-IDA-VEN represents an effective regimen, particularly in adverse risk ND and R/R AML patients and as an effective bridge to HSCT.
Naval Daver, Jessica K. Altman, Joseph Maly, et al.
Authors Conclusion from the Abstract: Ven plus Gilt achieved a very high overall rate of marrow and blood blast elimination and mCRc rate (84%) in this expansion cohort of heavily pretreated FLT3mut+ pts, the majority of whom had prior FLT3 TKI exposure. Using similar response assessment criteria, the high mCRc rate here suggests substantially greater antileukemic activity from Ven plus Gilt compared with single-agent Gilt. Cytopenias were prominent but manageable with dose interruption/modification on subsequent cycles. Nonhematologic toxicities were modest, and the combination was well tolerated.
Alexander E. Perl, Jessica K. Altman, Naoko Hosono, et al.
Authors Conclusion from the Abstract: Patients with R/R AML who received prior TKIs (midostaurin or sorafenib) were able to achieve remission with gilteritinib. High response rates with gilteritinib were observed in heavily pre-treated FLT3-mutation–enriched patients in the CHRYSALIS trial who received prior TKIs. Higher response rates with gilteritinib than with SC were observed in prior TKI–treated patients with FLT3 mutations in the ADMIRAL trial.
Ahmad S. Alotaibi, Musa Yilmaz, Rashmi Kanagal-Shamanna, et al.
Authors Conclusion from the Abstract: Specific, and in some cases targetable, pathways of secondary resistance were noted at relapse post type I and II FLT3 inhibitors, and possibly post specific combination partners. Understanding these differences and selecting type I or type II inhibitors with the optimal combination partner to target specific scenarios, may improve response durations. FLT3 mutations may no longer be detectable at relapse post FLT3i-based therapies highlighting the importance of repeated FLT3 testing at relapse.