Blinatumomab in pediatric acute lymphoblastic leukemia: one center experience
https://doi.org/10.18705/2782-3806-2024-4-2-156-169
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Abstract
Background. Despite the successes achieved in the treatment of B-cell acute lymphoblastic leukemia (B-ALL), overcoming the toxicity of standard chemotherapy regimens and the treatment of relapsed/refractory (r/r) forms of the disease remains relevant. The most promising option is to use immunotherapy (IT), including a monoclonal antibody blinatumomab (BM). The purpose of the study. To analyze indications of using, as well as efficacy and tolerability of BM in children with V-ALL.
Materials and methods. From April 2016 to January 2024 a retrospective assessment of using of BM in children with B-ALL in the chemotherapy department of oncohematological diseases and TCM for children in Almazov National Medical Research Centre was performed.
Results. The study included 53 patients, including 28 (53 %) girls and 25 (47 %) boys with median age of 7,7 (2,08–19,8) years. Indications for using of BM were as follows: (1) consolidation of remission (CR) with primary ALL (n = 17, 32 %); (2) persistence of minimal residual disease (MRD) (n = 23, 43 %) after completion of chemotherapy (CT) induction or before the stage of allogeneic haematopoietic stem cell transplantation (alloHSCT); (3) replacement of the standard CR due to the previous toxicity of СT or other contraindications to its implementation (n = 12, 23 %); (4) salvage therapy for r/r ALL (n = 1, 1,9 %). The status of MRD-negative remission after the 1st course of IT was achieved in 89 % of cases. Therapy using BM in a patient with the r/r ALL and total blast infiltration of the bone marrow was effective and facilitated reducing the tumor population to 7,2% by day 15 of therapy, however, there was a fatal outcome due to development and progression of preexisted severe infection. The most common variants of grade III–IV toxicity were leuko-/neutropenia (28 %) and neurotoxicity (3,7 %). BM dose reduction for the purpose of relieving toxicity was required in 19 % of patients, while the median days of therapy with dose reduction was 4. Corticosteroids were used for this purpose in 11 % of cases, antibacterial therapy — in 13 %. At the time of results evalution, there were no relapses of the disease in the study group. The article analyzes the international experience of using BM in patients with B-ALL.
Conclusion. Our experience and the presented literature data demonstrate a reasonable expansion of indications for using of BM in children with B-ALL with high efficacy and satisfactory toxicity profile.
About the Authors
N. V. MuliarovaRussian Federation
Muliarova Natalia V., resident, Department of pediatric oncohematology and BMT
Akkuratova str., 2, Saint Petersburg, 197341
A. Yu. Smirnova
Russian Federation
Smirnova Anna Yu., pediatric oncologist, Department of pediatric oncohematology and BMT
Saint Petersburg
S. I. Lapaeva
Russian Federation
Lapaeva Svetlana I., hematologist, Department of pediatric oncohematology and BMT
Saint Petersburg
Yu. K. Toshina
Russian Federation
Toshina Yulia K., pediatric oncologist, Department of pediatric oncohematology and BMT
Saint Petersburg
Yu. V. Dinikina
Russian Federation
Dinikina Yulia V., PhD, Head Department of pediatric oncohematology and BMT
Saint Petersburg
References
1. Pfister SM, et al. A summary of the inaugural WHO classification of pediatric tumors: transitioning from the optical into the molecular era //Cancer discovery. 2022. Vol. 12. No. 2. P. 331-355.
2. Ferlay J, et al. Cancer statistics for the year 2020: An overview //International journal of cancer. 2021. Vol. 149. No. 4. P. 778-789.
3. Moorman AV, et al. Time to cure for childhood and young adult acute lymphoblastic leukemia is independent of early risk factors: long-term follow-up of the UKALL2003 trial //Journal of Clinical Oncology. 2022. Vol. 40. No. 36. P. 4228-4239.
4. Jeha S, et al. Improved CNS control of childhood acute lymphoblastic leukemia without cranial irradiation: St Jude Total Therapy Study 16 //Journal of Clinical Oncology. 2019. Vol. 37. No. 35. P. 3377.
5. Inaba H, Pui CH. Advances in the diagnosis and treatment of pediatric acute lymphoblastic leukemia // Journal of clinical medicine. 2021. Vol. 10. No. 9. P. 1926.
6. Lew G, et al. Outcomes after late bone marrow and very early central nervous system relapse of childhood B-acute lymphoblastic leukemia: a report from the Children’s Oncology Group phase III study AALL0433 //Haematologica. 2021. Vol. 106. No. 1. P. 46.
7. Locatelli F, et al. Effect of blinatumomab vs chemotherapy on event-free survival among children with high-risk first-relapse B-cell acute lymphoblastic leukemia: a randomized clinical trial //Jama. 2021. Vol. 325. No. 9. P. 843-854.
8. Li B, et al. Therapy-induced mutations drive the genomic landscape of relapsed acute lymphoblastic leukemia //Blood, The Journal of the American Society of Hematology. 2020. Vol. 135. No. 1. P. 41-55.
9. Ekpa QL, et al. A Review of Acute Lymphocytic Leukemia (ALL) in the Pediatric Population: Evaluating Current Trends and Changes in Guidelines in the Past Decade //Cureus. 2023. Vol. 15. No. 12.
10. Lejman M, et al. Targeted Therapy in the Treatment of Pediatric Acute Lymphoblastic Leukemia - Therapy and Toxicity Mechanisms //International Journal of Molecular Sciences. 2021. Vol. 22. No. 18. P. 9827.
11. Schmiegelow K, et al. Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy //F1000Research. 2017. Vol. 6.
12. Elitzur S, et al. Blinatumomab as a bridge to further therapy in cases of overwhelming toxicity in pediatric B-cell precursor acute lymphoblastic leukemia: report from the Israeli Study Group of Childhood Leukemia //Pediatric Blood & Cancer. 2019. Vol. 66. No. 10. P. e27898.
13. Mengxuan S, Fen Z, Runming J. Novel treatments for pediatric relapsed or refractory acute B-cell lineage lymphoblastic leukemia: precision medicine era // Frontiers in Pediatrics. 2022. Vol. 10. P. 923419.
14. Logan AC. Measurable residual disease in acute lymphoblastic leukemia: How low is low enough? //Best Practice & Research Clinical Haematology. 2022. Vol. 35. No. 4. P. 101407.
15. Truong TH, et al. Allogeneic hematopoietic stem cell transplantation for children with acute lymphoblastic leukemia: shifting indications in the era of immunotherapy //Frontiers in Pediatrics. 2021. Vol. 9. P. 782785.
16. Olsson RF, et al. Primary graft failure after myeloablative allogeneic hematopoietic cell transplantation for hematologic malignancies Leukemia. 2015. Vol. 29. No. 8. P. 1754-1762.
17. Inaba H, Pui CH. Immunotherapy in pediatric acute lymphoblastic leukemia //Cancer and Metastasis Reviews. 2019. Vol. 38. No. 4. P. 595-610.
18. Queudeville M, Ebinger M. Blinatumomab in pediatric acute lymphoblastic leukemia - from salvage to first line therapy (a systematic review) //Journal of clinical medicine. 2021. Vol. 10. No. 12. P. 2544.
19. Mocquot P, et al. The pharmacology of blinatumomab: state of the art on pharmacodynamics, pharmacokinetics, adverse drug reactions and evaluation in clinical trials //Journal of Clinical Pharmacy and Therapeutics. 2022. Vol. 47. No. 9. P. 1337-1351.
20. Ojemolon PE, et al. Cytokine release syndrome following blinatumomab therapy //Cureus. 2022. Vol. 14. No. 1.
21. Jen EY, et al. FDA approval: blinatumomab for patients with B-cell precursor acute lymphoblastic leukemia in morphologic remission with minimal residual disease //Clinical Cancer Research. 2019. Vol. 25. No. 2. P. 473-477.
22. von Stackelberg A, et al. Phase I/phase II study of blinatumomab in pediatric patients with relapsed/ refractory acute lymphoblastic leukemia //Journal of Clinical Oncology. 2016. Vol. 34. No. 36. P. 4381-4389.
23. Locatelli F, et al. Blinatumomab in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia: RIALTO expanded access study final analysis //Blood advances. 2022. Vol. 6. No. 3. P. 1004-1014.
24. Zeng Y, Katsanis E. Potential niche indications for blinatumomab as a bridge to hematopoietic cell transplantation //Bone Marrow Transplantation. 2017. Vol. 52. No. 12. P. 1671-1673.
25. Clinicaltrials.gov. Blinatumomab in Pediatric B-cell Acute Lymphoblastic Leukemia (ALL) With Minimal Residual Disease (MRD). Available at: www.clinicaltrials. gov (NCT04604691).
26. Clinicaltrials.gov. Diagnosed From 0 to 365 Days of Life (ALL-Baby-2021). Available at: www.clinicaltrials. gov (NCT05029531).
27. Cinicaltrials.gov. Blinatumomab Maintenance Following Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Lymphoblastic Leukemia. Available at: www.clinicaltrials.gov (NCT02807883).
28. Brown PA, et al. A randomized phase 3 trial of blinatumomab vs. chemotherapy as post-reinduction therapy in high and intermediate risk (HR/IR) first relapse of B-acute lymphoblastic leukemia (B-ALL) in children and adolescents/young adults (AYAs) demonstrates superior efficacy and tolerability of blinatumomab: a report from Children’s Oncology Group Study AALL1331 //Blood. 2019. Vol. 134. P. LBA-1.
29. Locatelli F, et al. Effect of blinatumomab vs chemotherapy on event-free survival among children with high-risk first-relapse B-cell acute lymphoblastic leukemia: a randomized clinical trial //Jama. 2021. Vol. 325. No. 9. P. 843-854.
30. Clesham K, et al. Blinatumomab for infant acute lymphoblastic leukemia //Blood, The Journal of the American Society of Hematology. 2020. Vol. 135. No. 17. P. 1501-1504.
31. Hodder A, et al. Blinatumomab As Toxicity Sparing First Line Treatment of Children and Young Persons with B-Precursor Acute Lymphoblastic Leukaemia (B-ALL) // Blood. 2022. Vol. 140. No. Supplement 1. P. 8987-8988.
32. Li AM, et al. Blinatumomab associated seizure risk in patients with Down syndrome and B-lymphoblastic leukemia: an interim report from Children’s Oncology Group (COG) study AALL1731 // Blood. 2021. Vol. 138. P. 2304.
33. Rabin KR, et al. Treatment-Related Mortality (TRM) in children with down syndrome (DS) and B-lymphoblastic leukemia (B-ALL): an interim report from the children’s oncology group trials AALL0932 and AALL1131 //Blood. 2015. Vol. 126. No. 23. P. 2502.
34. Buitenkamp TD, et al. Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group //Blood, The Journal of the American Society of Hematology. 2014. Vol. 123. No. 1. P. 70-77.
35. Sora F, et al. Blinatumomab as a successful and safe therapy in Down syndrome patients with relapsed/ refractory b-precursor acute lymphoblastic leukaemia: case reports and literature review //Pediatric blood & cancer. 2021. Vol. 68. No. 7. P. e29044.
36. Collignon C, et al. Temporary contraindication to chemotherapy due to toxicity: blinatumomab’s effectiveness in paediatric patients with B-acute lymphoblastic leukaemia //British journal of haematology. 2023. Vol. 201. No. 4. P. e42-e45.
37. van der Sluis IM, et al. Blinatumomab added to chemotherapy in infant lymphoblastic leukemia //New England Journal of Medicine. 2023. Vol. 388. No. 17. P.
38. -1581. 38. Pieters R, et al. Outcome of infants younger than 1 year with acute lymphoblastic leukemia treated with the interfant-06 protocol: results from an international phase III randomized study //Journal of clinical oncology. 2019. Vol. 37. No. 25. P. 2246-2256.
39. Elitzur S, et al. Blinatumomab as a bridge to further therapy in cases of overwhelming toxicity in pediatric B‐cell precursor acute lymphoblastic leukemia: report from the Israeli Study Group of Childhood Leukemia //Pediatric Blood & Cancer. 2019. Vol. 66. No. 10. P. e27898.
40. Zeng Y, Katsanis E. Potential niche indications for blinatumomab as a bridge to hematopoietic cell transplantation //Bone Marrow Transplantation. 2017. Vol. 52. No. 12. P. 1671-1673.
41. Queudeville M, et al. Blinatumomab in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia //European Journal of Haematology. 2021. Vol. 106. No. 4. P. 473-483.
42. Clinicaltrials.gov. Acute Lymphoblastic Leukemia Treatment Protocol Moscow-Berlin 2019 Pilot. The head of the protocol and principal investigator - Doctor of Medical Sciences, Professor A. I. Karachunsky. Available at: www.clinicaltrials.gov (NCT04723342).
43. Institute NC. Common terminology criteria for adverse events (CTCAE), version 5.0. National Cancer Institute; 2017, Nov 27. Available at: https://ctep.cancer.gov/protocolDevelopment/electronic_applications docs/CTCAE_v5_Quick_Reference_8.5x11.pdf. Common terminology criteria for adverse events (CTCAE), version 5.0. National Cancer Institute; 2017, Nov 27.
44. Zhao Y, et al. Tumor-intrinsic and-extrinsic determinants of response to blinatumomab in adults with B-ALL //Blood, The Journal of the American Society of Hematology. 2021. Vol. 137. No. 4. P. 471-484.
45. Mirfakhraie R, et al. All about blinatumomab: the bispecific T cell engager immunotherapy for B cell acute lymphoblastic leukemia //Hematology, Transfusion and Cell Therapy. 2023.
46. ‐mpatzidou ‐, et al. Insights from the Greek experience of the use of Blinatumomab in pediatric relapsed and refractory acute lymphoblastic leukemia patients //Neoplasma. 2020. Vol. 67. No. 6. P. 1424-1430.
47. Philipp N, et al. T-cell exhaustion induced by continuous bispecific molecule exposure is ameliorated by treatment-free intervals //Blood, The Journal of the American Society of Hematology. 2022. Vol. 140. No. 10. P. 1104-1118.
48. Wei AH, et al. Biomarkers associated with blinatumomab outcomes in acute lymphoblastic leukemia //Leukemia. 2021. Vol. 35. No. 8. P. 2220-2231.
49. Chauvet P, et al. Combining blinatumomab and donor lymphocyte infusion in B-ALL patients relapsing after allogeneic hematopoietic cell transplantation: a study of the SFGM-TC //Bone marrow transplantation. 2023. Vol. 58. No. 1. P. 72-79.
50. Muriano F, et al. P350: Blinatumomab and donor lymphocyte infusion (DLI) for molecular relapse after hematopoietic stem cell transplantation in pediatric patients //HemaSphere. 2022. Vol. 6. P. 250-251.
51. Clinicaltrials.gov. A Phase 2 Study of Blinatumomab in Combination With Nivolumab, a Checkpoint Inhibitor of PD-1, in B-ALL Patients Aged ≥ 1 to 31 Years Old With First Relapse. Available at: www. clinicaltrials.gov (NCT04546399).
52. Choi HJ, et al. Combination therapy with chemotherapy, donor lymphocyte infusion with concurrent Blinatumomab in relapsed/refractory acute precursor B-lymphoblastic leukemia //Journal of Pediatric Hematology/Oncology. 2021. Vol. 43. No. 2. P. e280-e283.
53. Xie J, et al. Short-course blinatumomab for refractory/relapse precursor B acute lymphoblastic leukemia in children //Frontiers in Pediatrics. 2023. Vol. 11.
54. Collignon C, et al. Temporary contraindication to chemotherapy due to toxicity: blinatumomab’s effectiveness in paediatric patients with B-acute lymphoblastic leukaemia //British journal of haematology. 2023. Vol. 201. No. 4. P. e42-e45.
Review
For citations:
Muliarova N.V., Smirnova A.Yu., Lapaeva S.I., Toshina Yu.K., Dinikina Yu.V. Blinatumomab in pediatric acute lymphoblastic leukemia: one center experience. Russian Journal for Personalized Medicine. 2024;4(2):156-169. (In Russ.) https://doi.org/10.18705/2782-3806-2024-4-2-156-169. EDN: OUOTXZ
ISSN 2782-3814 (Online)