New therapies in AML
Alexander Perl, Giovanni Martinelli, Jorge Cortes, Andreas Neubauer,
GILTERITINIB SIGNIFICANTLY PROLONGS OVERALL SURVIVAL IN PATIENTS WITH FLT3-MUTATED (FLT3MUT+) RELAPSED/REFRACTORY (R/R) ACUTE MYELOID LEUKEMIA (AML): RESULTS FROM THE PHASE 3 ADMIRAL TRIAL
Conclusion: In patients with R/R FLT3mut+ AML, the potent, selective FLT3 inhibitor gilteritinib resulted in significantly longer overall survival and higher response rates compared with chemotherapy and had a favorable safety profile. These results change the treatment paradigm for salvage therapy of R/R FLT3mut+ AML and establish gilteritinib as the new standard of care.
Peter Westervelt, Gail J. Roboz, Jorge E. Cortes, Jessica K. Altman, et al.
SAFETY AND CLINICAL ACTIVITY OF AMV564, A CD33/CD3 T-CELL ENGAGER, IN PATIENTS WITH RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA (AML): UPDATED RESULTS FROM THE PHASE 1 FIRST-IN-HUMAN TRIAL
Conclusion: AMV564 is well-tolerated and demonstrates anti-leukemic activity through T-cell engagement using a 14-day administration schedule. AMV564 has a unique PK profile with a gradual increase in drug concentrations and thus the potential for better controlled T-cell activation.
David Sallman, William Donnellan, Adam Asch, Daniel Lee, et al.
THE FIRST-IN-CLASS ANTI-CD47 ANTIBODY HU5F9-G4 IS ACTIVE AND WELL TOLERATED ALONE OR IN COMBINATION WITH AZACITIDINE IN AML AND MDS PATIENTS: INITIAL PHASE 1B RESULTS
Conclusion: 5F9+AZA is a novel immunotherapy blocking a key macrophage/cancer checkpoint. It is well tolerated with promising activity in AML/MDS patients including rapid CRs with MRD negativity. Adding 5F9 to cytotoxic agents may be a promising treatment strategy. An expansion cohort is ongoing (NCT03248479). Funded by Forty Seven and California Institute for Regenerative Medicine.
Pierre Fenaux, Marco Gobbi, Patricia L Kropf, Jiri Mayer, et al.
RESULTS OF ASTRAL-1 STUDY, A PHASE 3 RANDOMIZED TRIAL OF GUADECITABINE (G) VS TREATMENT CHOICE (TC) IN TREATMENT NAÏVE ACUTE MYELOID LEUKEMIA (TN-AML) NOT ELIGIBLE FOR INTENSIVE CHEMOTHERAPY (IC)
Conclusion: The trial did not achieve its primary endpoints of statistically significant superiority of G vs TC for CR or OS. However due to the large sample size and narrow 95% CI for OS difference, the trial suggests that G is an active drug with an overall similar efficacy and safety profiles to standard therapy. Potential benefit of G vs TC was observed in patients who were able to receive adequate treatment (>3 cycles), and those who achieved any CR. The significance of TP53 mutations needs to be further explored.
Walter Fiedler, Joerg Chromik, Stefanie Amberg, Maxim Kebenko, et al.
A PHASE II STUDY OF SELINEXOR PLUS CYTARABINE AND IDARUBICIN IN PATIENTS WITH RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA (AML)
Conclusion: Selinexor with cytarabine and idarubicin results in a high remission rate in patients with R/R AML with unfavorable risk factors and should be further studied in a larger, randomized phase III trial.
Naveen Pemmaraju, Andrew Lane, Kendra Sweet, Anthony Stein, et al.
RESULTS OF PIVOTAL PHASE 2 CLINICAL TRIAL OF TAGRAXOFUSP (SL-401) IN PATIENTS WITH BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM (BPDCN)
Conclusion: This clinical trial was the largest prospectively designed trial dedicated to patients with BPDCN. The study demonstrated high response rates that were generally achieved early in the course of treatment and maintained over multiple cycles of therapy. The safety profile of tagraxofusp was predictable and manageable. CLS was identified as the most serious TRAE and the tagraxofusp prescribing information includes management guidelines that were developed and implemented during the trial. Tagraxofusp is approved in the US for the treatment of BPDCN and a MAA is under review in the EU.
ENASIDENIB ASSOCIATED WITH IMPROVED SURVIVAL COMPARED WITH STANDARD OF CARE FOR R/R AML PATIENTS WITH AN IDH2 MUTATION BASED ON DATA FROM STUDY AG221-C-001 AND A REVIEW OF PATIENT CHARTS IN FRANCE
Conclusion: Patients with R/R IDH2-mutated AML not eligible for HSCT who were treated with enasidenib on study had improved survival compared with patients receiving SoC in a real-world setting. Future studies are needed to validate these findings using other data sources, to compare enasidenib with specific treatments and to assess the comparative efficacy of enasidenib for other outcomes.