Subgroup analysis by fitness criteria of patients (pts) with blastic plasmacytoid dendritic cell neoplasm (BPDCN) treated with first-line (1L) tagraxofusp (TAG).

Abstract

6531 Background: BPDCN, an aggressive orphan hematologic neoplasm, expresses CD123 and presents in skin, bone marrow, blood, and viscera. For pts eligible to undergo hematopoietic cell transplantation (HCT), the 1L treatment goal is to rapidly induce a durable complete response (CR) before HCT. TAG is a first-in-class CD123-targeted therapy with a well-characterized and manageable safety profile without cumulative myelosuppression and the only drug approved to treat BPDCN. In 1L pts with a median age of 68 yrs, TAG has demonstrated, in a phase 1/2 pivotal trial with prespecified/multisystem response criteria, a 75% overall response rate, 24.9-month (mo) median duration of CR/clinical CR (CRc), and the ability to bridge 51% of pts with CR/CRc to HCT (Pemmaraju, JCO 2022). Notably, multi-agent intensive chemotherapy (IC) prior to HCT is still used, particularly in young fit pts, despite short- and long-term toxicity/myelosuppression and despite short durations of response (DOR). Also, many pts with BPDCN are ineligible for IC before HCT. We assess outcomes, based on pretreatment comorbidity burden, across HCT-specific comorbidity index (HCT-CI; Sorror, JCO 2007) fitness groups for pts who received 1L TAG for BPDCN in the pivotal trial (NCT02113982). Methods: Pts who received 1L TAG 12 µg/kg IV on days 1-5 of a 21-day cycle (C) were retrospectively assigned to categories by HCT-CI score (0 [low], 1-2 [intermediate; int] and 3+ [high]) per baseline medical history, concomitant medications, and labs. Outcomes included best response, time to response (TTR), DOR, overall survival (OS), HCT rate, treatment-related adverse events (TRAEs), and capillary leak syndrome (CLS). Results: 65 pts were scored as HCT-CI low (n=15), int (n=22), or high (n=28). Median age was 61, 67.5, and 70 yrs, respectively; disease was more extensive in high-risk pts. Objective responses (80%, 68%, 79%) were high regardless of HCT-CI group, with CR/CRc rates of 73%, 59%, and 46%. Median TTR was similar; median DOR was longer in low and int (24.9 mo/not reached [NR]) vs high (3.9 mo). HCT rates were 33%, 45%, and 21%; pre-transplant CR/CRc rates were 100%, 90%, and 83% with median DOR NR. Median OS in HCT pts was 38.4 mo, NR, and NR. In each group, most common Grade 3-4 TRAEs were thrombocytopenia and increased ALT/AST; most were in C1 and transient. Two deaths due to CLS occurred in int pts. Grade 3-4 CLS occurred in 0%, 9%, and 4% of pts; all CLS events were in C1 and all grade 1-4 CLS events resolved. Conclusions: 1L TAG BPDCN treatment yielded high response rates regardless of HCT-CI fitness, with a similar safety profile across HCT-CI groups. TAG enabled bridge to HCT across all fitness groups, including pts with high risk possibly ineligible for IC, as TAG is not associated with prolonged myelosuppression seen with IC. These results affirm TAG as the SOC in 1L treatment for the majority of pts with BPDCN. Clinical trial information: NCT02113982 .