Findings from a recent study support current recommendations to treat patients with BPDCN with tagraxofusp or hyper-CVAD as first-line treatments, then with allogeneic stem cell transplant if patients are eligible.
Conventional and intensive chemotherapy regimens, as well as tagraxofusp (SL-401, Elzonris, Stemline), offer comparable outcomes as first-line treatments for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). Patients who go on to have an allogenic stem cell transplant have significantly longer overall survival with this cancer known to have dismal outcomes, according to a study published July 28 in Blood Advances.1
A rare hematologic malignancy, BPDCN commonly involves skin and bone marrow. The cancer also often impacts lymph nodes and the spleen. BPDCN is universally positive for CD4, CD56 and CD123.
Oncologists have had limited success treating patients with BPDCN with conventional chemotherapies used to treat non-Hodgkin lymphoma, acute lymphoblastic leukemia or acute myeloid leukemia. Among those treatments are: cyclophosphamide, doxorubicin hydrochloride, oncovin and prednisone (CHOP) or hyper-fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose cytarabine and methotrexate (hyper-CVAD).
Tagraxofusp, a CD123-directed cytotoxin of recombinant human interleukin-3 fused to a truncated diphtheria toxin, is the first treatment approved by the U.S. Food and Drug Administration that is indicated for BPDCN in adults and children ages two years and older. The intravenous treatment has had promising results, including in one trial an overall response rate of 90% in previously untreated BPDCN patients. Still, the authors of this new study noted that data on the optimal first-line therapy for BPDCN patients is lacking.
Allogeneic hematopoietic stem cell transplantation has been associated with significantly improved survival, especially when BPDCN patients are allografted in their first complete remission. Not many patients are eligible for stem cell transplant, given the average age for BPDCN diagnosis is around 70 years, authors of the Blood Advances study write.
Authors of the single institution retrospective study analyzed data on 49 consecutive patients with BPDCN, 42 of which had some form of treatment. Twelve patients in the study received first-line treatment with tagraxofusp, 10 with CHOP and 11 with hyper-CVAD.
They found the hyper-CVAD regimen was associated with the highest complete response rate at 91%, compared to 50% with CHOP-based treatment and 50% with tagraxofusp. Patients treated with the hyper-CVAD regimen also had longer progression-free survival than patients receiving the other two treatment types. But the differences were not statistically significant.
There was no significant overall survival difference between patients treated with tagraxofusp compared to other chemotherapy first-line treatments.
Those patients who received allogeneic stem cell transplant had significantly longer overall survival than those who did not.
“Collectively, these observations suggest that both [tagraxofusp] and hyper CVAD could be a reasonable option as the first-line treatment with the understanding that associated toxicities differ among these therapies,” the authors wrote.
The findings support current recommendations to treat patients with BPDCN with tagraxofusp or hyper-CVAD as first-line treatments, then with allogeneic stem cell transplant if patients are eligible.
“…our findings require cautious interpretation and need to be validated in the larger prospective studies. In addition, optimal sequence of treatments and combination strategies remain to be investigated in future studies,” they write.
One of the study authors Mohamed A. Kharfan-Dabaja is a consultant for Daiichi Sankyo. The remaining authors have no disclosures.
1 Yun S, Chan O, Kerr D, et al. Survival outcomes in blastic plasmacytoid dendritic cell neoplasm by first-line treatment and stem cell transplant. Blood Adv. 2020;4(14):3435-3442.