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540 Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): Long-Term Outcomes and Novel Observations from a Large BPDCN Cohort

Program: Oral and Poster Abstracts
Type: Oral
Session: 613. Acute Myeloid Leukemias: Clinical and Epidemiological: Long-term Outcomes in Clinically Defined Subgroups of Patients with Acute Myeloid Leukemia
Hematology Disease Topics & Pathways:
Research, Acute Myeloid Malignancies, health outcomes research, Clinical Research, Diseases, Myeloid Malignancies
Sunday, December 11, 2022: 1:15 PM

Naveen Pemmaraju, MD1, Hagop Kantarjian, MD2, Joseph D. Khoury, MD, FCAP3, Nitin Jain, MD4, Muzaffar H Qazilbash, MD5, Sanam Loghavi, MD6, Sherry A. Pierce, BSN, BA1*, Keyur P. Patel, MBBS, PhD6, Guillermo Garcia-Manero, MD7, Elias Jabbour, MD1, Naval Daver, MD8, Gautam Borthakur, MD1 and Marina Konopleva, MD9*

1Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
2Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
3University of Nebraska Medical Center, Omaha, NE
4Department of Leukemia, MD Anderson Cancer Center, Houston, TX
5Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
6Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX
7Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX
8MD Anderson Cancer Center, Houston, TX
9Hematology/Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN), is an ultra-rare, clinically aggressive, CD123-overexpressing hematologic malignancy now reclassified in the 5th edition WHO under dendritic cell and histiocytic neoplasms (Khoury J Leukemia 2022). BPDCN is characterized by involvement of 4 major compartments: skin, bone marrow, lymph nodes, and central nervous system (CNS). BPDCN has been historically associated with a lack of treatment options, dismal outcomes (median OS 8-16 months). Now, in the modern treatment era, with CD123-based and combination therapies, emerging data and a number of significant clinical/translational breakthroughs have led to progress in this rare disease field (Pemmaraju N JCO 2022; Pemmaraju N Blood Adv 2022). In this analysis, we aim to describe long-term patient characteristics and outcomes in one of the largest ongoing, single-institution, prospectively followed group of patients (pts) with BPDCN in the world.

Patient Characteristics: All pts ages ≥ 18 years with a confirmed pathological diagnosis of BPDCN and treated at our institution were included in this analysis. During Oct 1998-July 2022, 118 pts with BPDCN were identified. Median age was 66 years [range 19-86 years]. 81% were male. At presentation to our institution: n=78 untreated; n=40 had prior therapy (median # prior therapies = 1 [1-5]). Bone marrow (BM) was involved in 75 (64%), skin-only in 41 (35%), lymph node-only in 2 (2%). In addition to CD4+ and CD56+ tumor immunophenotype demonstrated: TCL-1+ (77/77 tested) and CD123+ in 100%. Cytogenetics among 106 pts available: diploid (74%), complex (22%), del (12p) in 2%, miscellaneous (2%). Median BM blast count was 8% [0-95]. Historically, as there has been no standard of care therapeutic approach, a variety of frontline chemotherapy regimens were administered over time (including in this cohort: CD123-based; ALL-based; AML-based; CHOP/lymphoma-based; HMA+VEN based; other regimens).

Results, overall cohort (n=118): The median follow-up time was 23 months [4.1 - 91 mo]. Median # of chemotherapy regimens was 1 [1-6]. Median overall survival (OS) was 23 mo [0.9 -158.0 mo]. 78 (66%) pts died, with the most common cause of death being multi-organ failure. Skin-only pts with BPDCN: Remarkably, in this long-term f/u, there was no statistically significant difference between skin (n=41) vs BM involved BPDCN (n=75) in terms of either OS (20 mo vs 23 mo) or CR1 (21 vs 38 mo). SCT: 40 pts (33%) received stem cell transplant (SCT) during CR1. The median OS for pts receiving SCT was statistically significantly superior at 66 mo [5.3-90.8 mo] vs a median OS for non-SCT group in CR1 (n=31) of 23 mo [4.1-158.0], p =0.003. CNS involvement BPDCN: Notably, in this longer f/u of our series, we found that a high rate, 33%, of our pts had CSF+ at any time during the course of their BPDCN, with the vast majority of cases detected on routine/asymptomatic lumbar punctures. Prior or concomitant hematologic malignancies (PCHM): The occurrence of PCHM remains quite common in BPDCN, making up 24% of our total BPDCN population, with MDS/CMML representing the most common PCHM.

Next-generation Sequencing (NGS): A molecular gene panel via NGS on BM specimens was done in n=80; 60 (75%) had TET2 abnormality (standard mutation=36, standard+variant=2, variants=22), which was the most common molecular abnormality among our BPDCN cohort. There was no statistically significant difference in terms of OS or CR1 in pts with known TET2 mutations/variants vs all others/not done. The second most common mutation was ASXL1 in 38%, followed by RAS mutations in 19%.

Conclusions: This longer-term analysis (med f/u ~ 2 years) of a large, ongoing cohort of pts with BPDCN reveals several important findings including continued overall similar long-term outcomes in skin-only vs BM-involved BPDCN; significant OS improvement in CR1 for younger/fit pts who are able to proceed to SCT when available; a strikingly high incidence of CSF+ in BPDCN which is a higher incidence than previously recognized, and has led to our practice-changing approach of standard incorporation of routine LP with IT chemo for all pts with BPDCN; and a notably common occurrence of PCHM in BPDCN to be aware of in both diagnostic and treatment paradigms. With median OS still only ~2 years, BPDCN remains a highly aggressive hematologic malignancy still in need of active clinical/translational research and novel therapeutic approaches.

Disclosures: Pemmaraju: Plexxikon: Research Funding; Affymetrix: Research Funding; SagerStrong Foundation: Research Funding; LFB Biotechnologies: Honoraria; Roche Diagnostics: Honoraria; Cellectis: Research Funding; Daiichi Sankyo: Research Funding; Samus Therapeutics: Research Funding; Pacylex Pharmaceuticals: Consultancy; Novartis: Honoraria, Research Funding; Incyte: Research Funding; MustangBio: Honoraria; AbbVie: Honoraria, Research Funding; Stemline Therapeutics: Honoraria, Research Funding. Kantarjian: Astellas Health: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Research Funding; KAHR Medical Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Research Funding; ImmunoGen: Research Funding; Novartis: Honoraria, Research Funding; Ipsen Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; NOVA Research: Honoraria; Ascentage: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Daiichi-Sankyo: Consultancy, Research Funding; Takeda: Honoraria. Jain: Cellectis: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Other: Travel Support, Research Funding; Incyte Corporation: Research Funding; Cellectis: Honoraria, Research Funding; Servier Pharmaceuticals LLC: Research Funding; Precision Biosciences: Consultancy, Honoraria, Other: Travel Support, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Travel Support, Research Funding; Pharmacyclics, Inc.: Consultancy, Honoraria, Other: Travel Support, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding; Novalgen: Research Funding; Loxo Oncology: Research Funding; Medisix: Research Funding; Genentech, Inc.: Consultancy, Honoraria, Other: Travel Support, Research Funding; Janssen Pharmaceuticals, Inc.: Consultancy, Honoraria, Other: Travel Support; Pfizer: Research Funding; Dialectic Therapeutics: Research Funding; Newave: Research Funding; TransThera Sciences: Research Funding; Beigene: Honoraria; TG Therapeutics: Honoraria; MEI Pharma: Honoraria; Ipsen: Honoraria; CareDx: Honoraria; Adaptive Biotechnologies: Consultancy, Honoraria, Other: Travel Support, Research Funding; ADC Therapeutics: Research Funding; BMS: Consultancy, Honoraria, Other: Travel Support, Research Funding; Takeda: Research Funding; Mingsight: Research Funding; Aprea Therapeutics: Research Funding; Fate Therapeutics: Research Funding. Loghavi: Astellas: Research Funding; Guidepoint: Consultancy; GLG: Consultancy; QualWorld: Consultancy; PeerView: Honoraria; Amgen: Research Funding; Abbvie: Consultancy, Current equity holder in publicly-traded company; Caris: Consultancy; BluePrint Medicine: Consultancy; Daiichi Sankyo: Consultancy. Garcia-Manero: Aprea: Honoraria; Astex: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Curis: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Acceleron Pharma: Consultancy; Gilead Sciences: Research Funding; Genentech: Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding. Jabbour: Adaptive Biotechnologies: Other: Advisory Role, Research Funding; Bristol Myers Squibb: Other: Advisory Role, Research Funding; Genentech: Other: Advisory Role, Research Funding; Pfizer: Other: Advisory Role, Research Funding; Amgen: Other: Advisory Role, Research Funding; Takeda: Other: Advisory Role, Research Funding; Spectrum: Research Funding; AbbVie: Other: Advisory Role, Research Funding. Daver: FATE Therapeutics: Research Funding; Amgen: Consultancy, Research Funding; ImmunoGen: Consultancy, Research Funding; Celgene: Consultancy; Glycometrics: Research Funding; Jazz: Consultancy; Novimmune: Research Funding; Novartis: Consultancy; Arog: Consultancy; Trovagene: Research Funding; Pfizer: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Servier: Consultancy, Research Funding; Gilead Sciences, Inc.: Consultancy, Research Funding; Trillium: Consultancy, Research Funding; Hanmi: Consultancy, Research Funding; Agios: Consultancy; Shattuck: Consultancy; Syndax: Consultancy; BMS: Consultancy, Research Funding; Daiichi-Sankyo: Consultancy, Research Funding. Borthakur: Catamaran Bio, Abbvie, PPD Development, Protagonist Therapeutics, Janssen: Consultancy; Astex Pharmaceuticals, Ryvu, PTC Therapeutics: Research Funding; Pacylex, Novartis, Cytomx, Bio Ascend: Membership on an entity's Board of Directors or advisory committees.

OffLabel Disclosure: BPDCN has only one FDA approved agent. all others are by definition off label.

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