Efficacy and safety of pivekimab sunirine in blastic plasmacytoid dendritic cell neoplasm in patients with prior or concomitant hematologic malignancy: Results from the cadenza study

Abstract Introduction: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy that primarily involves skin, bone marrow, and lymph nodes. All BPDCN blasts overexpress CD123, making the alpha chain of the IL-3 receptor (IL-3Ra) a key target for therapeutic interventions. Pivekimab sunirine (PVEK) is a first-in-class antibody-drug conjugate composed of a high-affinity anti-CD123 antibody, a cleavable linker, and an indolinobenzodiazepine pseudodimer (IGN) payload that alkylates DNA and causes single strand breaks without crosslinking. Previously it was shown that among patients (pts) with CD123-positive BPDCN and no prior exposure to systemic therapy who were treated with PVEK monotherapy (frontline, 1L; N=33), 70% (95% CI, 51.3–84.4) demonstrated a composite complete response (CR; CR + clinical CR [CRc, CR with minimal skin abnormality]), with a median overall survival (OS) and duration of response (DoR) of 16.6 (11.4–not reached [NR]) and 9.8 (4.6–NR) months, respectively (Pemmaraju et al., 2025). Approximately 20% of pts with BPDCN may have prior or concomitant hematologic malignancy (PCHM), representing a more difficult-to-treat population than de novo BPDCN, and these pts may not be able to achieve full hematologic recovery due to the impact of the underlying malignancy. Here we report a subgroup analysis from the CADENZA study (NCT03386513) on outcomes in pts with PCHM. Methods: In the open-label, international, multicenter, phase 1/2 CADENZA study, adults with BPDCN received PVEK 0.045 mg/kg intravenously (<30-min infusion) on Day 1 of a 21-day cycle. The primary endpoint was CR+CRc rate in 1L de novo pts. The key secondary endpoint was duration of CR+CRc in 1L de novo pts. Additional secondary endpoints were time to CR+CRc; overall response rate (ORR); OS; percentage of pts bridged to post-treatment stem cell transplant (SCT); and frequency and severity of adverse events (AE) in overall 1L pts (de novo and PCHM cohorts). Results: As of 02 October 2024, 33% (n=11/33) of 1L pts with BPDCN had PCHM. Among 1L pts with PCHM, the median (range) age was 73 (66–84) years; 46% were ≥75 years of age; 91% were male; and 64% had Eastern Cooperative Oncology Group performance status = 1. At baseline, all pts had Grade ≤3 thrombocytopenia and skin lesions, and disease involvement in bone marrow (n=6 [55%]), lymph nodes (n=4 [36%]), and peripheral blood (n=2 [18%]). The most common types of PCHM included myelodysplastic syndromes (n=5 [45%]) and chronic myelomonocytic leukemia (n=4 [36%]). The median (range) number of treatment cycles and duration of treatment were 7 (3–20) and 25.7 (9.0–66.1) weeks, respectively. Disease response (95% CI) was achieved in a majority of pts; CR+CRc was 63.6% (30.8%–89.1%) with a median (95% CI) DoR of 9.2 (3.0–12.8) months, and CR+CRc+CRh (CRh, complete remission with partial hematologic recovery) and ORR were both 90.9% (58.7%–99.8%). Median (95% CI) OS in all pts with PCHM was 17.0 (8.3–NR) months. Five pts bridged to SCT, with a median time to SCT of 37 (range, 26–136) days; 4/5 (80%) pts with PCHM who proceeded to SCT had a best response of CR+CRc. Pts ≥75 years old (n=5) had a median (95% CI) ORR of 80.0% (28.4%–99.5%). The most common (≥25% of pts) any grade treatment-emergent AEs were peripheral edema (81.8%); hypokalemia and thrombocytopenia/decreased platelet count (all 54.5%); fatigue, anemia, insomnia, and hypoalbuminemia (all 36.4%); neutropenia, nausea, and decreased weight (all 27.3%); and increased alanine aminotransferase, aspartate aminotransferase, and blood bilirubin (all 27.3%). Conclusions: For this population of pts with PCHM with complex disease management and limited treatment options, response rates and duration of response with PVEK treatment were similar to the de novo BPDCN population in the CADENZA study. Median OS in the overall 1L population was not impacted by pts with PCHM. Importantly, almost half of pts with PCHM transitioned to SCT, despite being older and more frail, representing a potential breakthrough therapeutic option for this high-risk BPDCN pt subgroup.