AML-262 Pivekimab Sunirine (PVEK, IMGN632) Triplet With Azacitidine and Venetoclax Shows Broad Activity in Adverse Genetic Subsets of Relapsed/Refractory Acute Myeloid Leukemia and Reduced Infusion-Related Reactions.
Journal Article (Journal Article)
CONTEXT: Pivekimab sunirine (PVEK, IMGN632) is a first-in-class ADC comprising a CD123 high-affinity antibody, a cleavable linker, and an IGN (indolinobenzodiazepine pseudodimer) payload. PVEK with azacitidine (AZA) and venetoclax (VEN) is a novel triplet that has demonstrated anti-leukemia activity in relapsed/refractory AML patients. OBJECTIVE: Evaluate the anti-leukemia activity in genetic subgroups of AML and safety of the triplet. INTERVENTION: Patients with relapsed/refractory AML received PVEK+AZA+VEN in a three-drug escalation over a 28-day cycle: PVEK 0.015 or 0.045 mg/kg day 7, AZA 50 or 75 mg/m2 days 1-7, and VEN 400 mg for 8, 14, or 21 days. RESULTS: Twenty-nine patients (median age 67 y, ELN adverse 62%, prior VEN 48%) were in higher-intensity cohorts (PVEK 0.045 mg/kg and/or VEN for 14 or 21 days). The overall response rate (ORR) was 59% (4 CR, 6 CRh, 1 CRp, 6 MLFS) and the composite complete remission rate (CCR, CR+CRh+CRp+CRi) was 38%. Higher rates are seen in patients with FLT3-ITD (n=9, ORR 89%, CCR 78%), IDH2 (n=4, ORR 75%, CCR 75%), and WT1 (n=7, ORR 57%, CCR 43%) mutations. Lower rates are seen in patients with monosomy 7/abn7q (n=6, ORR 17%, CCR 17%), TP53 (n=4, ORR 25%, CCR 25%), and ASXL1 (n=6, ORR 67%, CCR 17%) deletions or mutations. The safety profile for the PVEK triplet is similar to AZA+VEN. No VOD, TLS, or CRS was reported. IRRs were reported in 33% (n=17, one grade 4) of patients given 1 dose of dexamethasone (8 mg) as premedication (n=51); these IRRs were most frequently tachycardia and chills, with no anaphylactic reactions reported. Following the data cut-off, there was a second grade 4 IRR, and the prophylactic regimen was increased with two additional doses of dexamethasone on the day prior to the PVEK dose. The IRR rate has dropped to 8% (3 of 38), with no grade 3+; all were grades 1-2 that resolved with limited intervention (P<0.01). CONCLUSIONS: The PVEK triplet with AZA+VEN demonstrates anti-leukemic activity across multiple high-risk genetic subsets of relapsed/refractory AML. Prophylactic steroids added on day -1 have significantly reduced IRRs. Expansion cohorts are now enrolling for untreated and relapsed AML patients (NCT04086264).
- Daver, N; Montesinos, P; Aribi, A; Martinelli, G; Altman, JK; Wang, ES; Roboz, GJ; Burke, PW; Gaidano, G; Walter, RB; Thomas, X; Jeyakumar, D; DeAngelo, DJ; Erba, HP; Todisco, E; Begna, K; Advani, A; Gastaud, L; de la Fuente, A; Curti, A; Mendez, LM; Vyas, P; Boissel, N; Vey, N; Recher, C; Longval, T; Platzbecker, U; Kapp-Schwörer, S; Schliemann, C; Konopleva, M; Torres, L; Sallman, DA; Marcucci, G; Marconi, G; Kantarjian, H; Sloss, CM; Malcolm, KE; Zweidler-McKay, PA; Sweet, K
- October 2022
Volume / Issue
- 22 Suppl 2 /
Start / End Page
- S231 - S232
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)
- United States