Type: Oral
Session: 615. Acute Myeloid Leukemias: Clinical and Epidemiological: Treatments and Outcomes in AML in Specific Age Groups, and in Blastic Plasmacytoid Dendritic Cell Neoplasms
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, ALL, Acute Myeloid Malignancies, AML, Adult, Elderly, Chemotherapy, Supportive Care, Diseases, Treatment Considerations, Lymphoid Malignancies, Non-Biological therapies, Young adult , Myeloid Malignancies, Pharmacology, Study Population, Human
BPDCN (Blastic Plasmacytoid Dendritic Cell Neoplasm) is a rare and aggressive hematological malignancy, with heterogeneous therapeutic approaches. Few data are available regarding efficacy of treatment strategies in real world. The study aims to elucidate the optimal management strategies for BPDCN and identify patients who could benefit from curative treatments and novel therapies. This includes the CD33 or CD123 targeted molecules, as tagraxofusp, which has demonstrated activity as a front-line therapy.
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 three groups based on the therapeutic approaches: intensive, non-intensive, and supportive care only treatments. Patients receiving intensive schedules were subclassified into 3 groups: treated with Acute Myeloid Leukemia (AML)-like regimens, Acute Lymphocytic Leukemia (ALL)-like regimens, and lymphoma-like regimens. Non-intensive treatments were divided into 4 groups: AML-like, ALL-like, lymphoma-like (including local radiotherapy or intralesional chemotherapy), and targeted agents (anti-CD33 or anti-CD123). 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. The different demographic variables of the various treatment subgroups were compared to identify differences.
Results
From 200 patients with follow-up and therapy records, 132 patients (66%) received intensive treatment, 53 (26%) received non-intensive (including anti-CD33 or CD123 targeted agents), and 15 (8%) received supportive care. Among intensive treatment 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 (10 AZA, 5 AZA-VEN, 4 LDAC, and 2 fludarabine+LDAC); 18 (34%) CD123 or CD33 targeted molecules, 9 (16%) ALL-like therapies (vincristine and dexamethasone-based), and 5 (10%) lymphoma-like, including 3 with radiotherapy or intralesional chemotherapy.
As expected, significant difference was found between intensive vs. non-intensive subgroups in age (57 vs. 71 years, p<0.001). There were significant differences in some demographic variables among AML-like vs. ALL-like vs. lymphoma-like vs. targeted agents subgroups: age (63 vs. 56 vs. 63 vs. 66 years; p=0.03), cutaneous involvement (71 vs. 81 vs. 89 vs. 100 %; p=0.04) and CD123 positive (90 vs. 96 vs. 70 vs. 100 %; p=0.02).
Median OS in patients receiving intensive therapy was 15.8 (95% CI 9.7-22.0) months (n=132). From them, 91 patients reached CRc (79%) vs 24 who did not (21%), with a median OS of 32.7 (95% CI 19.0-46.4) vs 7.9 (95% CI 6.2-9.6) months, respectively (p=0.02). Regarding non-intensive treatment subgroup (n=53), median OS was 8.0 (95% CI 4.7-11.4) months. It was longer in the 27 patients who achieved CRc (60%) than in 18 who did not (40%): 17.2 (95% CI 11.2-23.1) vs 7.0 (95% CI 5.6-8.5) months (p=0.005).
There were no statistically significant differences in OS among patients treated with intensive AML-like, ALL-like, and lymphoma-like approaches (10.1 vs. 34.2 vs. 19.1 months, respectively; p=0.08). Regarding non-intensive schedules, median OS were 10.1, 7.3, 3.6 and 6.9 months in the AML-like, ALL-like, lymphoma-like and targeted therapies groups, respectively. No statistically significant differences were observed (p=0.28).
Conclusion
Our findings emphasize the importance of achieving CRc to improve the prognosis of these difficult-to-treat patients. Our study also shows that patients treated with intensive treatment regimens for BPDCN had better OS than those treated with non-intensive therapies. The differences between treatment subgroups, such as age at diagnosis, among others, could influence the differences in OS. Larger studies and observational protocols are needed to identify best upfront regimens for BPDCN.
Disclosures
This study was partially funded by Menarini.
Disclosures: Salamero: Astellas, Jazz, BMS: Consultancy; Jazz, Abbvie: Honoraria. Rodriguez Macias: Astellas: Consultancy, Honoraria, Speakers Bureau; Servier: Consultancy, Honoraria, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Otsuka: Consultancy, Honoraria, Speakers Bureau; BMS-Celgene: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Speakers Bureau. Tormo: AbbVie, Gilead, Pfizer, Astellas, BMS: Honoraria; Janssen, AbbVie, Jazz: Other: Travel grant for attending meetings; SOBI: Other: Data Safety Monitoring Board. Montesinos: Novartis: Consultancy, Research Funding, Speakers Bureau; Jazzpharma: Consultancy, Research Funding, Speakers Bureau; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: research support, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: research support, Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: research support, Research Funding, Speakers Bureau; Daiichi Sankyo, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: research support, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: research support, Research Funding, Speakers Bureau; Kura Oncology: Consultancy; Syndax: Consultancy; Glycomimetics: Consultancy.