Indeterminate dendritic cell neoplasm (IDCN) is an exceedingly rare and mostly cutaneous histiocytosis, frequently associated with other hematopoietic malignancies. We report 2 cases of multilesional cutaneous IDCN. A 55-year-old male with no associated malignancy and complete response to ultraviolet phototherapy; and a 72-year-old male with chronic myelomonocytic leukemia (CMML). Both cases showed histiocytoid cytology, positivity for CD1a and no expression of langerin or BRAF . With our patients, the literature describes 79 cases of IDCNs, including 65 (82%) with only skin involvement, 7 cases (9%) with involvement of skin and a second site, 5 cases (6%) involving lymph nodes only, 1 splenic lesion and 1 systemic disease. Seventeen cases (22%) were associated with other hematopoietic malignancies, most commonly CMML (6 cases), follicular lymphoma (4 cases) and acute myeloid leukemia (3 cases). All IDCNs associated with myeloid malignancies were limited to the skin, while most cases associated with lymphoma were limited to lymph nodes. Reported responses of cutaneous lesions to ultraviolet phototherapy are encouraging, while systemic chemotherapy is appropriate for clinically aggressive cases and treatment of associated malignancies. Recognition of the clinico-morphologic spectrum of IDCNs should prevent misdiagnoses and prompt investigation of possible associated neoplasms.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with dismal clinical outcomes. Conventional chemotherapies such cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose cytarabine and methotrexate (CVAD) have been commonly used for the BPDCN treatment until a recent study showed promising outcomes in patients treated with SL-401 (Tagraxofusp). In this single-institution retrospective study, we identified a total of 49 consecutive BPDCN patients. Among 42 patients who received treatment, hyper-CVAD regimen was associated with higher complete response rate compared with CHOP-based regimens or SL-401 (91% vs 50% vs 50%), although the difference did not achieve statistical significance. Furthermore, there was no significant overall survival (OS) difference between patients treated with SL-401 vs other chemotherapies as their first-line treatment (hazard ratio = 1.597; 95% CI, 0.460-5.548; P = .431). Of note, patients who received allogeneic stem cell transplant (allo-SCT) had significantly longer OS (hazard ratio = 0.160; 95% CI, 0.0453-0.56; P = .041). Extent of disease (skin vs bone marrow vs both) or younger age (<60 years old) did not have significant prognostic impact on OS. Collectively, our study confirmed the survival benefit of allo-SCT and suggests that conventional and intensive chemotherapies such as CHOP and hyper-CVAD as well as SL-401 would be comparable first-line choice for the BPDCN patients.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with dismal clinical outcomes. Conventional chemotherapies were previously shown to have some clinical efficacy, however, long-term outcomes of BPDCN patients remain poor. In a recent clinical trial, SL-401 demonstrated an overall response rate (ORR) of 90% in previously untreated BPDCN patients. Despite promising outcomes observed in SL-401 studies, there remains a lack of data regarding the optimal first-line therapy. In this single institution retrospective study, we explored the survival outcomes based on front-line treatment and allogeneic stem cell transplant (allo-SCT). A total of 49 patients with confirmed diagnosis of BPDCN were included in the study. Median age at diagnosis was 71.4 (32.0-91.4) years with a male predominance (82%). Among these, 11 (22%) patients had concurrent hematologic neoplasms at the time of BPDCN diagnosis. The most common site of disease involvement was skin (n=42, 86%) followed by bone marrow (BM) (n=32, 65%), lymph node (LN) (n=13, 27%), and nasopharynx (n=2, 4%) with 14 (29%) and 5 (10%) patients having skin and BM involvement only, respectively. Of note, 17 (35%) patients had both skin and BM disease and 8 (16%) had simultaneous skin, BM, and LN involvement. In the front-line setting, CHOP-based regimens, hyper-CVAD, and SL-401 were used in 10 (20%), 11 (22%), and 12 (24%) patients, respectively. The median cycle number of SL-401 treatment was 6 (1-73). Allo-SCT was performed in 10 (20%) patients and 4 (8%) patients received autologous stem cell transplant (auto-SCT). Transplant was performed following first-line therapy in 11 patients (CR, n=10; PR, n=1) and second-line therapy in 3 patients (CR, n=3). Among 21 vs. 12 patients who received chemotherapy vs. SL-401 as their first-line therapy, a total of 11 (52%) and 3 (25%) patients underwent transplant. A total of 23 (55%), 13 (31%), and 6 (14%) patients achieved a complete response (CR), partial response (PR), and progressive disease (PD), respectively. CR rate was higher in patients who were treated with hyper-CVAD compared to others, however, it was not statistically significant (50% in CHOP-based regimens vs. 91% in hyper-CVAD, P=0.064; 50% in SL-401 vs. 91% in hyper-CVAD, P=0.069). The median PFS was 9.9 months and the median OS was not reached when all patients were included for the analyses. In the subgroup analyses, patients who were treated with hyper-CVAD had longest PFS compared to patients treated with CHOP-based regimens (HR=0.217, 95%CI=0.050-0.933, P=0.003) or SL-401 (HR=0.385, 95%CI=0.126-1.179, P=0.075) although the PFS difference between hyper-CVAD and SL-401 did not reach the statistical significance. There was no PFS difference between SL-401 and CHOP-based regimen treated groups (HR=0.931, 95%CI=0.321-2.70, P=0.894). In the OS analysis based on first-line therapy, there was no difference between patients treated with SL-401 compared to patients treated with chemotherapy regimens (HR=1.597, 95%CI=0.460-5.548, P=0.431). Further, there was no OS difference between individual types of front-line therapies (P=0.678). In contrast, patients who received allo-SCT showed significantly longer OS outcomes compared to patients with no transplant (HR=0.160, 95%CI=0.0453-0.56, P=0.041). Additional OS analyses based on age (<60 vs. ≥60) (HR=0.481, 95%CI=0.146-1.582, P=0.258), ASXL1 mutation (HR=1.705, 95%CI=0.2773-10.48, P=0.5649), or presence of previous or concurrent hematologic malignancy (HR=2.97, 95%CI=0.65-13.57, P=0.1602) did not show any statistical difference. In a multivariate Cox model (adjusting for age, front-line therapy, gender, and transplant) allo-SCT was significant factor for OS (HR=0.137, 95%CI=0.020-0.959, P=0.045). In conclusion, our study supports current recommendations of using SL-401 or hyper-CVAD as the first-line treatments followed by consolidation with allo-SCT in the eligible responders to induction therapy to further improve survival outcomes in BPDCN patients. Disclosures Lancet: Abbvie: Consultancy; Agios Pharmaceuticals: Consultancy, Honoraria; Astellas Pharma: Consultancy; Celgene: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; ElevateBio Management: Consultancy; Jazz Pharmaceuticals: Consultancy; Pfizer: Consultancy. kharfan-Dabaja:Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy. Sokol:Kyowa/Kirin Inc.: Membership on an entity's Board of Directors or advisory committees; EUSA Pharma: Consultancy, Honoraria, Speakers Bureau; Kymera Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematopoietic malignancy originating from precursor plasmacytoid dendritic cells. Clinically, patients usually present with skin lesions and simultaneous involvement of peripheral blood, bone marrow, lymph node, spleen and central nervous system. Median survival from diagnosis has been reported to range from 9 to 12 months (Julia F et al. Br J Dermatol. 2013;579-86). The optimal treatment for BPDCN has not been established yet. Majority of patients demonstrate response to lymphoma or acute lymphoblastic leukemia-like chemotherapy induction regimens. A consolidation with autologous or allogeneic hematopoietic stem cell transplantation may improve outcome of selected patients. Limited data are available regarding prognostic and predictive factors. In this study we analyzed clinical and laboratory characteristics and assessed their impact on clinical outcome. Methods and Materials: Patients with diagnosis of BPDCN at Moffitt Cancer Center between 2000 and 2015 were retrieved from a clinical database. The diagnosis was confirmed by morphology, laboratory data, and immunopehnotying, according to 2008 WHO Classification of Hematopoietic Neoplasms. The relevant clinicopathologic features extracted from electronic medical records were recorded. Treatment modalities and responses to therapy were correlated with clinical outcomes. A univariate linear discriminant analysis was used for risk stratification. Overall survival was analyzed by Kaplan-Meier method. Results: We identified 24 patients with a median age of 74 years (range: 36-94 years) and a male:female ratio of 23:1. Mean hemoglobin was 11.83 2.48 g/dL; mean platelet count was 134 ± 84 k/µL; and mean white blood count was 6.34 ± 7.25 k/µL. Only one patient had an Eastern Cooperative Oncology Group (ECOG) performance status greater than 2. Four patients demonstrated skin lesions only. Twenty patients (83.3%) demonstrated extracutaneous or systemic involvements. Peripheral blood, bone marrow, lymph node, spleen and cerebrospinal fluid (CSF) involvements were found in 11 (45.8%), 16 (66.7%), 8(33.3%), and 4(17%) patients, respectively. Six of 20 (30%) patients with systemic involvement were treated with CHOP. Two of 6 patients were treated with hyper-CVAD followed by an allogeneic hematopoietic stem cell transplant. Autologous transplant was administered to one patient who was treated with both CHOP and ICE induction regimens. Median overall survival (OS) of the cohort was 49.9 months (95% CI, 19.9 - 81 months) and median follow up duration was 33.5 months (95% CI, 3-147 months). Statistical analysis showed the following parameters were not prognostic predictors of OS at diagnosis: hemoglobin level (<10 g/dL), leukocytosis (>11,000/ul), thrombocytopenia (<100,000/ul), age >60, peripheral blood and bone marrow involvement (p=0.51, p=0.278, p=0.684, p=0.9288, p=0.2074, and p=0.8633, respectively). Lymph node involvement at diagnosis was associated with a shorter OS compared to those without lymph node involvement (p=0.0305). CHOP versus more aggressive chemotherapies did not show difference in OS (p=0.8939). Bone marrow transplant (1 autologous and 2 allogeneic) showed a trend to have longer OS (86 versus 64 months; p=0.12). Conclusion: BPDCN has an aggressive biological behavior. Median overall survival of 49.9 months observed in our study compares favorably with OS of 12 months in previous reports. Lymph node involvement at diagnosis may have adverse impact on clinical outcomes. Larger scale studies are needed to identify risk factors that may have impact on outcomes and to establish standardized therapy in patients with BPDCN. Disclosures Sokol: Seatle Genetics: Research Funding; Spectrum: Consultancy; Celgene: Consultancy.