Clinical Features and Outcomes in 228 Patients Diagnosed with Blastic Plasmocytoid Dendritic Cell Neoplasm: A Pethema/PALG Study
Authors: Navarro Vicente Irene , Solana-Altabella Antonio , Sobas Marta , Serrano Josefina , Karasek Magdalena , Perez Encinas Manuel , Labrador Jorge , de la Fuente Cristina , Salamero Olga , Colmenares Gil Rafael , Castaño Tamara , Algarra Jesús Lorenzo , García-Fortes María , De Miguel Maria Dunia , Trigo Fernanda , Duarte Delfim , Pradillo Fernandez Virginia , Foncillas Maria Angeles , Noriega Concepcion Victor , Paúl Vidaller Pedro , Bernal Del Castillo Teresa , Bergua Burgues Juan Miguel , Rodriguez Macias Gabriela , Rodriguez Arboli Eduardo , Simon Isabel , Caminos Nerea , Esteban-Figuerola Ada , Brioso Infante Joana , Romero Monica Alejandra , Vallansot Rolando Omar , Targonski Lukasz , Ulenberg Emilia , Lewandowski Krzysztof , Armatys Anna , Guzicka-Kazmierczak Renata , Sobczyk-Kruszelnicka Małgorzata , Szczepaniak Andrzej , De Rueda Ciller Beatriz , Lavilla Esperanza , Garrastazul Sánchez Maria Paz , Solano Tovar Jackeline , Insua Vilas Cristina , Madrigal Toscano Maria Dolores , Lamarca Laura , Tormo Mar , Gil Cristina , Colorado Mercedes , Barrios García Manuel , Olivares Salaverri Matxalen , Costilla-Barriga Lisette , Rodriguez Veiga Rebeca , Lloret Madrid Pilar , Martinez Cuadron David , Montesinos Pau 
Published: December 2024

Background: BPDCN (Blastic Plasmacytoid Dendritic Cell Neoplasm) is a rare and aggressive hematological malignancy, but still few data are available on clinical-biological characteristics and treatment outcomes in real world.

Material: This multinational retrospective study performed by PALG and PETHEMA (EPI-BLAS study) groups registered BPDCN patients (WHO 2008 or 2016) from June 1999, onwards. We categorized patients into 3 groups based on the therapeutic approaches: intensive treatment, non-intensive treatment, and supportive care only treatment. We analyzed composite complete remission (CRc) after first-line and overall survival (OS). CRc was defined as the sum of full CR, clinical CR with cutaneous sequelae, clinical CR with hematologic partial response, and clinical CR with incomplete recovery.

Results: Overall, 232 BPDCN pts were registered among 21866 AML cases in the PETHEMA registry (0.11%), and 228 were evaluable. Most were male (77%), median age was 63 years old (range 17-90), and 45 (26%) had prior or concomitant neoplastic disease (53% of them had hematological neoplasms, including large granular lymphocytic leukemia (n=1), myelodysplastic syndromes (n=11), non-Hodgkin T-cell lymphoma (n=3), and chronic myelomonocytic leukemia(n=6)). Median hemoglobin level was 10.55 g/dL (range 5.5-16.8), white blood cell count was 6.55x 10^3/mL (0.1-163), platelet count was 94 x10^3/µL (6-457), peripheral blood blasts 18.5% (0-95), bone marrow blasts 54% (0-98), LDH 331.5 IU/L (111-4500), creatinine 0.9mg/dL (0.4- 8.2), uric acid level 5.2mg/dL (2.2- 13.8). As for extramedullary involvement,161 (80%) out of 202 with available data, had skin involvement, hepato or splenomegaly was found in 21%, 49% had lymphadenopathy and 80% presented with bone marrow affection. A lumbar puncture was performed at diagnosis in 110 (65%) patients of the 170 patients with available data; of them, 33 (30%) had infiltration. As per available immunohistochemistry/phenotype markers, CD123, CD56 and CD4 were positive in 160 (92%), 154 (83%), and 157 (87%) pts, respectively. First-line approach was available in 200 patients, 15 (7%) received supportive care; 132 (59%) intensive; and 53 (22%) non-intensive treatment. Among intensive group, 45 (34%) received AML-like (34 with 3+7, 9 FLAG-IDA, and 2 HAM); 60 (46%) ALL-like (55 HyperCVAD and 5 with PETHEMA-ALL), and 27 (20%) lymphoma-like (17 CHOP, 7 etoposide-based, 1 ABVD, and 2 bortezomib-based). The non-intensive group included 21 (40%) AML-like regimens (5 AZA-VEN, 2 FLUGA, 10 AZA, and 4 LDAC); 18 (34%) CD123 or CD33 targeted molecules, 9 (16%) ALL-like, 5 (10%) lymphoma-like, including 3 with radiotherapy or intralesional chemotherapy. Among 185 pts with active treatment, response was available in 162 pts, of whom 117 (72%) obtained CRc, while 14 pts (9%) died during induction (sepsis [n=8], multiorgan failure [n=3], bleeding [n=2], and pulmonary embolism [n=1]). Median OS of the entire cohort was 11.83 months [95% CI 08.76 - 14.90]. Median OS for patients who achieved CRc after first-line therapy was 27.47 months (95% CI: 15.08-39.85) and 7.03 months (95% CI: 3.79-10.28) for those not achieving CRc; p&lt;0.001. A total of 65 pts (55% of those in first CRc) were transplanted in first CRc (61 an allogeneic transplant, and 4 an autologous one). Median OS in patients who received a transplantation was 84.76 (95% CI 0.00- 173.49) months and in patients not transplanted was 14.80 (95% CI 10.22-19.38) months (p&lt;0.001).

Conclusion: Clinical and biological features were consistent with previous reports, although skin infiltration and CD123 expression were below expected. We show heterogeneity in therapeutic approaches, relatively high rate of CRc after front-line, and a sizable proportion of transplanted patients. However, median OS remains disappointing. Improvement of outcomes through well-defined treatment protocols and targeted agents is needed for this high unmet need disease.

Disclosures: The EPI-BLAs registry was partially funded by Menarini.