[Blinatumomab-based Combination Treatment for CD19-positive Acute Leukemia of an Ambiguous Lineage]

Overview

Journal Zhonghua Xue Ye Xue Za Zhi

Specialty Hematology

Date 2025 Jan 2

PMID 39746700

Authors

X X Wu

Z Yang

C Q Lu

X H Zhang

A N Sun

H F Zhou

D P Wu

M Miao

Affiliations

Soon will be listed here.

Abstract

Acute leukemia of ambiguous lineage (ALAL) is a rare type of acute leukemia and is extremely difficult to treat. Here, we present six patients with CD19-positive ALAL who were successfully treated with blinatumomab-based combination treatment in the front-line setting. Five were diagnosed with B-cell/myeloid mixed phenotype acute leukemia (MPAL) and one with B-cell/T cell MPAL. All six patients achieved complete remission after one cycle of blinatumomab combination treatment. Furthermore, 3 (50%) patients achieved MRD-negative (<0.01%) by flow cytometry and 2 (50%) of four patients with evaluable molecular MRD achieved molecular remission. At some point during the treatment, 5 (83.3%) patients achieved MRD negativity and all four patients with evaluable molecular MRD had molecular remission. The overall survival was 100%, and the event-free survival was 83.3% after a median follow-up time of 15 months. This study provides preliminary evidence that blinatumomab-based combination therapy is an effective and safe treatment for patients with CD19-positive ALAL in the front-line setting.

References

Durer S, Durer C, Shafqat M, Comba I, Malik S, Faridi W . Concomitant use of blinatumomab and donor lymphocyte infusion for mixed-phenotype acute leukemia: a case report with literature review. Immunotherapy. 2019; 11(5):373-378. PMC: 6439498. DOI: 10.2217/imt-2018-0104. View

Advani A, Moseley A, ODwyer K, Wood B, Fang M, Wieduwilt M . SWOG 1318: A Phase II Trial of Blinatumomab Followed by POMP Maintenance in Older Patients With Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia. J Clin Oncol. 2022; 40(14):1574-1582. PMC: 9084435. DOI: 10.1200/JCO.21.01766. View

Kantarjian H, Stein A, Gokbuget N, Fielding A, Schuh A, Ribera J . Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N Engl J Med. 2017; 376(9):836-847. PMC: 5881572. DOI: 10.1056/NEJMoa1609783. View

Pullarkat V, Lacayo N, Jabbour E, Rubnitz J, Bajel A, Laetsch T . Venetoclax and Navitoclax in Combination with Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma. Cancer Discov. 2021; 11(6):1440-1453. PMC: 9533326. DOI: 10.1158/2159-8290.CD-20-1465. View

Rossi J, Bernasconi A, Alonso C, Rubio P, Gallego M, Carrara C . Lineage switch in childhood acute leukemia: an unusual event with poor outcome. Am J Hematol. 2012; 87(9):890-7. DOI: 10.1002/ajh.23266. View

Maruffi M, Sposto R, Oberley M, Kysh L, Orgel E . Therapy for children and adults with mixed phenotype acute leukemia: a systematic review and meta-analysis. Leukemia. 2018; 32(7):1515-1528. PMC: 7508489. DOI: 10.1038/s41375-018-0058-4. View

Alcharakh M, Yun S, Dong Y, Vincelette N, Daud M, Manzoor S . Blinatumomab-induced donor T-cell activation for post-stem cell transplant-relapsed acute CD19-positive biphenotypic leukemia. Immunotherapy. 2016; 8(8):847-52. DOI: 10.2217/imt-2015-0023. View

Kim H . Mixed-phenotype acute leukemia (MPAL) and beyond. Blood Res. 2017; 51(4):215-216. PMC: 5234227. DOI: 10.5045/br.2016.51.4.215. View

Mei M, Aldoss I, Marcucci G, Pullarkat V . Hypomethylating agents in combination with venetoclax for acute myeloid leukemia: Update on clinical trial data and practical considerations for use. Am J Hematol. 2018; 94(3):358-362. DOI: 10.1002/ajh.25369. View

10.

Bartram J, Balasch-Carulla M, Bhojaraja S, Adams S, Cheng D, Inglott S . Blinatumomab for paediatric mixed phenotype acute leukaemia. Br J Haematol. 2021; 195(2):289-292. DOI: 10.1111/bjh.17707. View

11.

Shimizu H, Yokohama A, Hatsumi N, Takada S, Handa H, Sakura T . Philadelphia chromosome-positive mixed phenotype acute leukemia in the imatinib era. Eur J Haematol. 2014; 93(4):297-301. DOI: 10.1111/ejh.12343. View

12.

Hrusak O, de Haas V, Stancikova J, Vakrmanova B, Janotova I, Mejstrikova E . International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia. Blood. 2018; 132(3):264-276. DOI: 10.1182/blood-2017-12-821363. View

13.

Munker R, Brazauskas R, Wang H, de Lima M, Khoury H, Gale R . Allogeneic Hematopoietic Cell Transplantation for Patients with Mixed Phenotype Acute Leukemia. Biol Blood Marrow Transplant. 2016; 22(6):1024-1029. PMC: 4867266. DOI: 10.1016/j.bbmt.2016.02.013. View

14.

Jabbour E, Short N, Jain N, Thompson P, Kadia T, Ferrajoli A . Hyper-CVAD and sequential blinatumomab for newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukaemia: a single-arm, single-centre, phase 2 trial. Lancet Haematol. 2022; 9(12):e878-e885. DOI: 10.1016/S2352-3026(22)00285-X. View

15.

El Chaer F, Ali O, Sausville E, Law J, Lee S, Duong V . Treatment of CD19-positive mixed phenotype acute leukemia with blinatumomab. Am J Hematol. 2018; 94(1):E7-E8. DOI: 10.1002/ajh.25317. View

16.

Bacchiarri F, Sammartano V, Santoni A, Raspadori D, Zappone E, Defina M . First reported case of secondary mixed phenotype acute leukemia after multiple myeloma. Am J Blood Res. 2021; 11(1):123-131. PMC: 8010609. View

17.

Wu D, Chen W, Chen Z, Li Q . Venetoclax Combined with Hypomethylating Agents for Treatment-Naïve B/Myeloid Mixed Phenotype Acute Leukemia. Case Rep Hematol. 2021; 2021:6661109. PMC: 7815380. DOI: 10.1155/2021/6661109. View

18.

Shi R, Munker R . Survival of patients with mixed phenotype acute leukemias: A large population-based study. Leuk Res. 2015; 39(6):606-16. DOI: 10.1016/j.leukres.2015.03.012. View

19.

Gokbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Faul C . Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018; 131(14):1522-1531. PMC: 6027091. DOI: 10.1182/blood-2017-08-798322. View