Tagraxofusp, azacitidine, and venetoclax (TAG-AZA-VEN) triplet therapy shows efficacy, tolerability, and transplant potential in patients with blastic plasmacytoid dendritic cell neoplasm, according to the results of a phase 2 trial presented during the 67th American Society of Hematology Annual Meeting and Exposition.
The researchers had previously evaluated the safety of the triplet combination in a phase 1b study for patients with acute myeloid leukemia. There is an urgent need in BPDCN, a rare and aggressive cancer, for more effective therapies; currently only tagraxofusp is approved by the US Food and Drug Administration for BPDCN.
In this phase 2 study presented, the trial enrolled 27 patients (median age 70; range 21-81), 16 of whom had previously untreated (1L) BPDCN and 11 of whom had relapsed or refractory BPDCN. Of the patient cohort, 93% were male. Ten of 27 (37%) patients had “skin-only” disease; others had additional sites of organ involvement. Six of 27 (22%) patients had asymptomatic CNS disease at study entry. In the relapsed or refractory cohort (n=11), seven had prior tagraxofusp and four prior transplant (three allo, one auto).
The median number of cycles received was 2.5 (range 1-14) in the 1L cohort, and 2 (range 1-5) in the relapsed or refractory cohort. Median follow-up in the 1L cohort was 20.4 months. In the relapsed or refractory cohort, all patients died in follow-up except one who remains on study at 39 months.
In the 1L cohort, 14 of 16 patients (88%) achieved composite CR (CR, n=8; CRi, n=6), with one PR and one not evaluable (early death). In the relapsed or refractory cohort, 7 of 11 patients (64%) achieved composite CR (CR, n=2; CRi, n=3; CRc, n=2).
In the 1L cohort, 10 of 16 (63%) went to allogeneic stem cell transplant directly following protocol therapy, including 10 of the 11 patients age <= 75. In the relapsed or refractory cohort, 6 of 11 (55%) went to allogeneic stem cell transplant.
Median overall survival was not reached in the 1L cohort, with both one- and two-year OS of 60%. Median progression-free survival in the 1L cohort was not reached, with one- and two-year PFS of 58%. In the relapsed or refractory cohort, median OS was 8.4 months, with one-year OS of 36% and two-year OS of 18%. Median PFS in the relapsed or refractory cohort was 6.3 months.
Treatment-related adverse events were similar to those in the TAG-AZA-VEN AML study, the researchers, led by Andrew Lane, MD, PhD, of Dana Farber Cancer Institute, reported in the abstract.
“Triplet therapy with TAG-AZA-VEN is effective and feasible in patients with previously untreated or R/R BPDCN, including in an older patient population,” the authors wrote. “The safety profile is consistent with prior studies of TAG and AZA/VEN. These data support TAG-AZA-VEN as an effective treatment option for patients with BPDCN.”
Funding was provided by Stemline Therapeutics.
