Results of Pivotal Phase 2 Clinical Trial of Tagraxofusp (SL-401) in Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Pemmaraju, Naveen; Lane, Andrew A.; Sweet, Kendra; Stein, Anthony S.; Vasu, Sumithira; Blum, William; Rizzieri, David A.; Wang, Eunice S.; Duvic, Madeleine; Spence, Sharon; Shemesh, Shay; Brooks, Christopher; Bergstein, Ivan; Chen, Janice; Dunn, Vanessa; McDonald, Peter R.; Sloan, John Mark; Lancet, Jeffrey E.; Kantarjian, Hagop M.; Konopleva, Marina

doi:10.1182/blood-2018-99-118966

Cited by 17 publications

(17 citation statements)

References 5 publications

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“…Although data is sparse, agents like tagraxofusp (SL-401) directed against interleukin-3 receptor CD123 provide a novel targeted treatment option 6 7 19. Food and Drug Administration (FDA) approved tagraxofusp on 21 December 2018 for BPDCN in adults and in paediatric patients ≥2 years of age after promising results of a multi-centre phase II clinical trial 20. In our case, the patient was offered the drug when it was not FDA approved as an experimental agent.…”

Section: Discussionmentioning

confidence: 97%

Blastic plasmacytoid dendritic cell neoplasm in the background of myeloproliferative disorder and chronic lymphocytic leukaemia

et al. 2019

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare haematological malignancy defined by concurrent expression of CD4, CD56, BCL-2 and CD123. The disease has a very poor prognosis and there are no well-established treatment guidelines. We describe a case of BPDCN in a 65-year-old female patient with myeloproliferative disorder (essential thrombocythemia) and chronic lymphocytic leukaemia. She presented with rapidly progressive facial and scalp lesions. Skin biopsy confirmed BPDCN and the imaging revealed widespread disease. Patient was started on hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) and intrathecal methotrexate. Due to progression on initial treatment, she was treated with decitabine and venetoclax (BCL-2 inhibitor). However, patient continued to deteriorate and died after 4 months from initial diagnosis. We emphasise on the clinical features, emerging treatment modalities and prognosis of BPDCN.

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Section: Discussionmentioning

confidence: 97%

Blastic plasmacytoid dendritic cell neoplasm in the background of myeloproliferative disorder and chronic lymphocytic leukaemia

et al. 2019

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“…In December 2018, Tagraxofusp-erzs gained FDA approval for treatment of BPDCN in adult and pediatric patients ≥2 years of age. The approval was based on results of a single arm study, STML-401-0114, in which the pivotal cohort of 13 treatment-naïve BPDCN patients, treated with Tagraxofusp-erzs monotherapy, showed a 54% composite complete remission (CRc) rate and safety was established in 94 patients with myeloid neoplasms [27,28].…”

Section: Targeting Cd123mentioning

confidence: 99%

New and Emerging Targeted Therapies for Pediatric Acute Myeloid Leukemia (AML)

Chen

Glasser

2020

Children

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The relapse rate for children with acute myeloid leukemia (AML) remains high despite advancements in risk classification, multi-agent chemotherapy intensification, stem cell transplantation, and supportive care guidelines. Prognosis for this subgroup of children with relapsed/refractory AML remains poor. It is well known that the ceiling of chemotherapy intensification has been reached, limited by acute and chronic toxicity, necessitating alternative treatment approaches. In the last several years, our improved understanding of disease biology and critical molecular pathways in AML has yielded a variety of new drugs to target these specific pathways. This review provides a summary of antibody drug conjugates (ADCs), small molecule inhibitors, and tyrosine kinase inhibitors with an emphasis on those that are currently under clinical evaluation or soon to open in early phase trials for children with relapsed/refractory AML.

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“…SL-401 has been granted "breakthrough therapy" designation by the United States Food and Drug Administration for the treatment of BPDCN. Pemmaraju et al presented the results of a pivotal phase-2 study of SL-401 in 45 patients with BPDCN in the frontline as well as in the relapsed/refractory setting [10]. The authors showed encouraging ORR of 90%, and a median OS which had not been reached when 29 patients were treated with a dose of 12 mcg/kg in the frontline setting [10].…”

Section: Sl-401mentioning

confidence: 99%

“…Pemmaraju et al presented the results of a pivotal phase-2 study of SL-401 in 45 patients with BPDCN in the frontline as well as in the relapsed/refractory setting [10]. The authors showed encouraging ORR of 90%, and a median OS which had not been reached when 29 patients were treated with a dose of 12 mcg/kg in the frontline setting [10]. Of note, 13 (45%) of 29 patients were bridged to a HCT (allo-HCT = 10, auto-HCT = 3) [10].…”

Section: Sl-401mentioning

confidence: 99%

“…In a pilot phase 1/2 study that included 11 patients with BPDCN, SL-401 yielded a major objective response in 7 (78%) of 9 evaluable cases; however, longterm durability was not observed in most patients, as responses were short-lived, with a median duration of only 5 months, with only one cycle of therapy for most patients treated on the study [9]. Results of the phase 2 study presented by Pemmaraju et al demonstrated high overall response rates (ORRs) of 90%, and a median OS which had not been reached after prescribing SL-401 in the frontline setting [10]. Moreover, 45% of treated cases were able to proceed to a hematopoietic cell transplant (HCT), mainly allogeneic hematopoietic cell transplant (allo-HCT), even when the median age of patients was 70 years.…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic Approaches for Blastic Plasmacytoid Dendritic Cell Neoplasm: Allogeneic Hematopoietic Cell Transplantation and Novel Therapies

Kharfan‐Dabaja¹,

Pemmaraju²,

Mohty³

2019

CHI

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a clinically aggressive hematologic malignancy derived from precursors of plasmacytoid dendritic cells. There is no established standard therapy for BPDCN and the efficacy of conventional chemotherapy is limited, with an anticipated median overall survival ranging from 8 to 14 months. No randomized controlled trials have ever been performed to evaluate the benefit of frontline consolidation with an allogeneic hematopoietic cell transplant (allo-HCT) in BPDCN. Yet, offering an allograft has become the de facto option in BPDCN, and remains the only known long-term curative option for these patients, even in the modern era of targeted therapies. In our opinion, allo-HCT is recommended as part of frontline consolidation, especially in patients achieving first complete remission and who are deemed capable of tolerating the procedure, as published data show 3-to 4-year progression-free survival ranging from 69% to 74% in this population. Prompt referral to a transplant center, at the time of a diagnosis of BPDCN, is important to confirm allo-HCT candidacy and to initiate the process of identifying a suitable human leukocyte antigen (HLA)-compatible donor. Because disease relapse remains a major concern, additional strategies, such as post-allograft consolidation/maintenance therapy, are certainly needed to help further improve outcomes. Finally, patients deemed ineligible to receive an allo-HCT, due to lack of response and/or poor performance status, should be considered for enrollment in clinical trials.

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Results of Pivotal Phase 2 Clinical Trial of Tagraxofusp (SL-401) in Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

Cited by 17 publications

References 5 publications

Blastic plasmacytoid dendritic cell neoplasm in the background of myeloproliferative disorder and chronic lymphocytic leukaemia

Blastic plasmacytoid dendritic cell neoplasm in the background of myeloproliferative disorder and chronic lymphocytic leukaemia

New and Emerging Targeted Therapies for Pediatric Acute Myeloid Leukemia (AML)

Therapeutic Approaches for Blastic Plasmacytoid Dendritic Cell Neoplasm: Allogeneic Hematopoietic Cell Transplantation and Novel Therapies

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