Tagraxofusp effective in patients with blastic plasmacytoid dendritic-cell neoplasm

Adults with untreated or relapsed blastic plasmacytoid dendritic-cell neoplasm demonstrated high response rates with tagraxofusp, according to phase 2 study results published in The New England Journal of Medicine.

The results served as the basis for the FDA’s approval of tagraxofusp-erzs (Elzonris, Stemline Therapeutics) in December for treatment of this patient population.

Blastic plasmacytoid dendritic-cell neoplasm is a rare, aggressive blood and bone marrow disease for which there historically has been no effective treatment. It is caused by altered plasmacytoid dendritic cells that overexpress interleukin-3 receptor subunit alpha.

Tagraxofusp is a CD123-targeting cytotoxin containing human interleukin-3 attached to truncated diphtheria toxin.

Naveen Pemmaraju, MD
Naveen Pemmaraju

“In adults with blastic plasmacytoid dendritic-cell neoplasm, tagraxofusp led to clinical responses regardless of whether patients had received previous therapy,” Naveen Pemmaraju, MD, associate professor in the department of leukemia at The University of Texas MD Anderson Cancer Center, said in a press release. “We observed high response rates, including an overall response rate of 90% among frontline-treated patients. These findings offer hope for patients who have had no treatments specific to this disorder.”

The nonrandomized, open label, multicohort study included 47 patients (median age, 70 years; range, 22-84) with untreated or relapsed blastic plasmacytoid dendritic-cell neoplasm who were enrolled between 2014 and 2017. Most patients (n = 32) had not received prior treatment for the disease.

Participants received an IV infusion of tagraxofusp at a dose of 7 g/kg or 12 g/kg on days 1 to 5 of each 21-day cycle. They remained on treatment until disease progression or intolerable toxicity.

The combined rate of complete response and clinical complete response in treatment-naive patients served as the primary outcome measure. Duration of response served as a secondary outcome.

Median follow-up was 19 months (range, 1-42).

Of the 29 treatment-naive patients who received tagraxofusp at a dose of 12 g/kg, 72% (95% CI, 53-87) achieved the primary outcome.

The overall response rate was 90%, with a median time to response of 43 days (range, 14-131). Of these patients, 45% proceeded to stem cell transplantation.

Survival probabilities were 59% at 18 months and 52% at 24 months.

Among the 15 patients who underwent prior treatment, the ORR was 67% (95% CI, 38-88), with a median time to response of 24 days (range, 17-48) and median duration of response of 2.8 months (range, 0.7-14). These patients had a median OS of 8.5 months.

Median duration of the primary outcome had not been reached at the time of analysis.

The most prevalent adverse events included increased levels of alanine aminotransferase (64%) and aspartate aminotransferase (60%), hypoalbuminemia (55%), peripheral edema (51%) and thrombocytopenia (49%).

Grade 3 or higher adverse events occurred in 78% of previously untreated patients and 87% of previously untreated patients.

Capillary leak syndrome, a serious adverse event, occurred in 19% of patients and was related to one death in each dose subgroup.

Two other clinical studies are investigating potential targeted treatments for blastic plasmacytoid dendritic-cell neoplasm, Andrew Lane, MD, PhD, director of the blastic plasmacytoid dendritic-cell neoplasm center at Dana-Farber Cancer Institute, said in a press release. One will evaluate venetoclax (Venclexta; AbbVie, Genentech), an inhibitor of the BCL-2 protein, and the other will analyze a therapy that fuses to the CD123 protein and supplies chemotherapy directly to the blastic plasmacytoid dendritic-cell neoplasm cells.

Andrew Lane, MD, PhD
Andrew Lane

“We can celebrate this new drug; it’s great to have approval,” Lane said. “Still, we continue to work on improving outcomes for patients.” – by Jennifer Byrne

Disclosures: Lane reports grants or personal fees from AbbVie, N-of-One and Stemline Therapeutics, as well as a patent, “Methods for determining and treating cellular resistance to ADP-ribosylating toxin,” pending. Pemmaraju reports grants and/or personal fees from Affymetrix, Celgene, Cellectis, Daiichi-Sankyo, Leukemia and Lymphoma Society, MustangBio, Novartis, Patient Power, Plexxicon, Roche Diagnostics, SagerStrong Foundation, Samus and Stemline Therapeutics. Please see the study for all other authors’ relevant financial disclosures.

Adults with untreated or relapsed blastic plasmacytoid dendritic-cell neoplasm demonstrated high response rates with tagraxofusp, according to phase 2 study results published in The New England Journal of Medicine.

The results served as the basis for the FDA’s approval of tagraxofusp-erzs (Elzonris, Stemline Therapeutics) in December for treatment of this patient population.

Blastic plasmacytoid dendritic-cell neoplasm is a rare, aggressive blood and bone marrow disease for which there historically has been no effective treatment. It is caused by altered plasmacytoid dendritic cells that overexpress interleukin-3 receptor subunit alpha.

Tagraxofusp is a CD123-targeting cytotoxin containing human interleukin-3 attached to truncated diphtheria toxin.

Naveen Pemmaraju, MD
Naveen Pemmaraju

“In adults with blastic plasmacytoid dendritic-cell neoplasm, tagraxofusp led to clinical responses regardless of whether patients had received previous therapy,” Naveen Pemmaraju, MD, associate professor in the department of leukemia at The University of Texas MD Anderson Cancer Center, said in a press release. “We observed high response rates, including an overall response rate of 90% among frontline-treated patients. These findings offer hope for patients who have had no treatments specific to this disorder.”

The nonrandomized, open label, multicohort study included 47 patients (median age, 70 years; range, 22-84) with untreated or relapsed blastic plasmacytoid dendritic-cell neoplasm who were enrolled between 2014 and 2017. Most patients (n = 32) had not received prior treatment for the disease.

Participants received an IV infusion of tagraxofusp at a dose of 7 g/kg or 12 g/kg on days 1 to 5 of each 21-day cycle. They remained on treatment until disease progression or intolerable toxicity.

The combined rate of complete response and clinical complete response in treatment-naive patients served as the primary outcome measure. Duration of response served as a secondary outcome.

Median follow-up was 19 months (range, 1-42).

Of the 29 treatment-naive patients who received tagraxofusp at a dose of 12 g/kg, 72% (95% CI, 53-87) achieved the primary outcome.

The overall response rate was 90%, with a median time to response of 43 days (range, 14-131). Of these patients, 45% proceeded to stem cell transplantation.

Survival probabilities were 59% at 18 months and 52% at 24 months.

Among the 15 patients who underwent prior treatment, the ORR was 67% (95% CI, 38-88), with a median time to response of 24 days (range, 17-48) and median duration of response of 2.8 months (range, 0.7-14). These patients had a median OS of 8.5 months.

Median duration of the primary outcome had not been reached at the time of analysis.

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The most prevalent adverse events included increased levels of alanine aminotransferase (64%) and aspartate aminotransferase (60%), hypoalbuminemia (55%), peripheral edema (51%) and thrombocytopenia (49%).

Grade 3 or higher adverse events occurred in 78% of previously untreated patients and 87% of previously untreated patients.

Capillary leak syndrome, a serious adverse event, occurred in 19% of patients and was related to one death in each dose subgroup.

Two other clinical studies are investigating potential targeted treatments for blastic plasmacytoid dendritic-cell neoplasm, Andrew Lane, MD, PhD, director of the blastic plasmacytoid dendritic-cell neoplasm center at Dana-Farber Cancer Institute, said in a press release. One will evaluate venetoclax (Venclexta; AbbVie, Genentech), an inhibitor of the BCL-2 protein, and the other will analyze a therapy that fuses to the CD123 protein and supplies chemotherapy directly to the blastic plasmacytoid dendritic-cell neoplasm cells.

Andrew Lane, MD, PhD
Andrew Lane

“We can celebrate this new drug; it’s great to have approval,” Lane said. “Still, we continue to work on improving outcomes for patients.” – by Jennifer Byrne

Disclosures: Lane reports grants or personal fees from AbbVie, N-of-One and Stemline Therapeutics, as well as a patent, “Methods for determining and treating cellular resistance to ADP-ribosylating toxin,” pending. Pemmaraju reports grants and/or personal fees from Affymetrix, Celgene, Cellectis, Daiichi-Sankyo, Leukemia and Lymphoma Society, MustangBio, Novartis, Patient Power, Plexxicon, Roche Diagnostics, SagerStrong Foundation, Samus and Stemline Therapeutics. Please see the study for all other authors’ relevant financial disclosures.