Blinatumomab (Blincyto) 35mcg: Mechanism, Dosing, and Clinical Use

Blinatumomab (Blincyto) is a bispecific T-cell engager (BiTE) antibody approved for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) and certain non-Hodgkin lymphomas. It works by linking CD3-positive T cells to CD19-positive B cells, triggering targeted immune-mediated cell death. The 35mcg dose is a common vial size, but clinical dosing is typically weight- or surface area-based and administered as a continuous infusion.

Mechanism of Action and Pharmacology

Blinatumomab binds simultaneously to CD19 on B cells and CD3 on T cells, forming a cytolytic synapse that leads to T-cell activation, proliferation, and serial lysis of malignant B cells. This mechanism is independent of T-cell receptor specificity and does not require MHC class I presentation, making it effective even in heavily pretreated or refractory cases (Zhu et al., 2016; Clements et al., 2019; Queudeville & Ebinger, 2021; Mocquot et al., 2022; Burt et al., 2018).

Dosing Regimens and Administration

• In adults, blinatumomab is usually given as a continuous intravenous infusion, with stepwise dosing to reduce cytokine release syndrome risk. Typical regimens start at 9 mcg/day for 7 days, then increase to 28 mcg/day for the remainder of the cycle (May & Glode, 2016; Zhu et al., 2016; Clements et al., 2019; Mocquot et al., 2022).
• Pediatric dosing is based on body surface area (e.g., 5 mcg/m²/day for 7 days, then 15 mcg/m²/day) (Von Stackelberg et al., 2016; Clements et al., 2019; Queudeville & Ebinger, 2021; Mocquot et al., 2022).
• Subcutaneous administration is under investigation and shows promise for convenience and efficacy (Jabbour et al., 2024).

Efficacy and Safety

Blinatumomab has demonstrated high response rates in relapsed/refractory ALL, with complete remission rates ranging from 32% to over 80% depending on patient population and disease status (Von Stackelberg et al., 2016; May & Glode, 2016; Przepiorka et al., 2015; Lu et al., 2024; Van Der Sluis et al., 2023; Topp et al., 2011). The most common serious adverse events are cytokine release syndrome and neurologic toxicity, which are generally manageable with stepwise dosing and supportive care (Zhu et al., 2016; Von Stackelberg et al., 2016; May & Glode, 2016; Przepiorka et al., 2015; Van Der Sluis et al., 2023; Mocquot et al., 2022; Nägele et al., 2017).

Blinatumomab Research Timeline and Key Topics

• 2011
  • 1 paper: (Topp et al., 2011)- 2015
  • 2 papers: (May & Glode, 2016; Przepiorka et al., 2015)- 2016
  • 3 papers: (Zhu et al., 2016; Von Stackelberg et al., 2016; Goebeler et al., 2016)- 2017
  • 1 paper: (Nägele et al., 2017)- 2018
  • 2 papers: (Burt et al., 2018; Gökbuget et al., 2018)- 2019
  • 3 papers: (Clements et al., 2019; Poh et al., 2019; Dufner et al., 2019)- 2021
  • 1 paper: (Queudeville & Ebinger, 2021)- 2022
  • 2 papers: (Mocquot et al., 2022; , 2022)- 2023
  • 3 papers: (Van Der Sluis et al., 2023; Hogan et al., 2023; Lantz et al., 2023)- 2024
  • 2 papers: (Jabbour et al., 2024; Lu et al., 2024)Figure 1: Timeline of key blinatumomab studies and clinical milestones.

Topic	Key Papers	Citations
Mechanism & Pharmacology	(Zhu et al., 2016; Clements et al., 2019; Queudeville & Ebinger, 2021; Mocquot et al., 2022; Burt et al., 2018)	(Zhu et al., 2016; Clements et al., 2019; Queudeville & Ebinger, 2021; Mocquot et al., 2022; Burt et al., 2018)
Adult ALL Efficacy	(May & Glode, 2016; Przepiorka et al., 2015; Lu et al., 2024; Topp et al., 2011)	(May & Glode, 2016; Przepiorka et al., 2015; Lu et al., 2024; Topp et al., 2011)
Pediatric ALL Efficacy	(Von Stackelberg et al., 2016; Queudeville & Ebinger, 2021; Van Der Sluis et al., 2023; Hogan et al., 2023)	(Von Stackelberg et al., 2016; Queudeville & Ebinger, 2021; Van Der Sluis et al., 2023; Hogan et al., 2023)
Dosing & Administration	(Zhu et al., 2016; Von Stackelberg et al., 2016; May & Glode, 2016; Clements et al., 2019; Jabbour et al., 2024; Mocquot et al., 2022)	(Zhu et al., 2016; Von Stackelberg et al., 2016; May & Glode, 2016; Clements et al., 2019; Jabbour et al., 2024; Mocquot et al., 2022)
Safety & Adverse Events	(Zhu et al., 2016; Von Stackelberg et al., 2016; May & Glode, 2016; Przepiorka et al., 2015; Van Der Sluis et al., 2023; Mocquot et al., 2022; Nägele et al., 2017)	(Zhu et al., 2016; Von Stackelberg et al., 2016; May & Glode, 2016; Przepiorka et al., 2015; Van Der Sluis et al., 2023; Mocquot et al., 2022; Nägele et al., 2017)

Figure 2: Table summarizing blinatumomab research focus areas.

Summary

Blinatumomab is a targeted immunotherapy with proven efficacy in relapsed/refractory B-cell ALL and some lymphomas. Its unique mechanism, stepwise dosing, and manageable safety profile have established it as a key option in both adult and pediatric settings. Ongoing research continues to refine its use and expand its indications.

References

Zhu, M., Wu, B., Brandl, C., Johnson, J., Wolf, A., Chow, A., & Doshi, S. (2016). Blinatumomab, a Bispecific T-cell Engager (BiTE®) for CD-19 Targeted Cancer Immunotherapy: Clinical Pharmacology and Its Implications. Clinical Pharmacokinetics, 55, 1271-1288. https://doi.org/10.1007/s40262-016-0405-4

Von Stackelberg, A., Locatelli, F., Zugmaier, G., Handgretinger, R., Trippett, T., Rizzari, C., Bader, P., O’Brien, M., Brethon, B., Bhojwani, D., Schlegel, P., Borkhardt, A., Rheingold, S., Cooper, T., Zwaan, C., Barnette, P., Messina, C., Michel, G., DuBois, S., Hu, K., Zhu, M., Whitlock, J., & Gore, L. (2016). Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia.. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 34 36, 4381-4389. https://doi.org/10.1200/JCO.2016.67.3301

May, M., & Glode, A. (2016). Blinatumomab: A novel, bispecific, T-cell engaging antibody.. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 73 1, e6-e13. https://doi.org/10.2146/ajhp150134

Clements, J., Zhu, M., Kuchimanchi, M., Terminello, B., & Doshi, S. (2019). Population Pharmacokinetics of Blinatumomab in Pediatric and Adult Patients with Hematological Malignancies. Clinical Pharmacokinetics, 59, 463 - 474. https://doi.org/10.1007/s40262-019-00823-8

Goebeler, M., Knop, S., Viardot, A., Kufer, P., Topp, M., Einsele, H., Noppeney, R., Hess, G., Kallert, S., Mackensen, A., Rupertus, K., Kanz, L., Libicher, M., Nagorsen, D., Zugmaier, G., Klinger, M., Wolf, A., Dorsch, B., Quednau, B., Schmidt, M., Scheele, J., Baeuerle, P., Leo, E., & Bargou, R. (2016). Bispecific T-Cell Engager (BiTE) Antibody Construct Blinatumomab for the Treatment of Patients With Relapsed/Refractory Non-Hodgkin Lymphoma: Final Results From a Phase I Study.. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 34 10, 1104-11. https://doi.org/10.1200/JCO.2014.59.1586

Przepiorka, D., Ko, C., Deisseroth, A., Yancey, C., Candau-Chacon, R., Chiu, H., Gehrke, B., Gomez-Broughton, C., Kane, R., Kirshner, S., Mehrotra, N., Ricks, T., Schmiel, D., Song, P., Zhao, P., Zhou, Q., Farrell, A., & Pazdur, R. (2015). FDA Approval: Blinatumomab. Clinical Cancer Research, 21, 4035 - 4039. https://doi.org/10.1158/1078-0432.CCR-15-0612

Queudeville, M., & Ebinger, M. (2021). Blinatumomab in Pediatric Acute Lymphoblastic Leukemia—From Salvage to First Line Therapy (A Systematic Review). Journal of Clinical Medicine, 10. https://doi.org/10.3390/jcm10122544

Jabbour, E., Zugmaier, G., Agrawal, V., Martínez-Sánchez, P., Roca, J., Cassaday, R., Böll, B., Rijneveld, A., Abdul-Hay, M., Huguet, F., Cluzeau, T., Díaz, M., Vučinić, V., González-Campos, J., Rambaldi, A., Schwartz, S., Berthon, C., Hernández-Rivas, J., Gordon, P., Brüggemann, M., Hamidi, A., Chen, Y., Wong, H., Panwar, B., Katlinskaya, Y., Markovic, A., & Kantarjian, H. (2024). Single agent subcutaneous blinatumomab for advanced acute lymphoblastic leukemia. American Journal of Hematology, 99, 586 - 595. https://doi.org/10.1002/ajh.27227

Lu, J., Qiu, H., Wang, Y., Zhou, X., Dai, H., Lu, X., Yang, X., Gu, B., Hong, M., Miao, M., Lu, R., Wang, J., Wu, Q., Xue, M., Wang, Y., Deng, A., Shen, Y., Liu, Y., Dou, X., Lei, Y., Wu, D., Zhu, Y., & Chen, S. (2024). Reduced-dose chemotherapy and blinatumomab as induction treatment for newly diagnosed Ph-negative B-cell precursor acute lymphoblastic leukemia: a phase 2 trial. Journal of Hematology & Oncology, 17. https://doi.org/10.1186/s13045-024-01597-8

Poh, C., Frankel, P., Ruel, C., Abedi, M., Schwab, E., Costello, C., Zain, J., Budde, L., William, B., Foss, F., Jonas, B., Rosenberg, A., Newman, E., & Tuscano, J. (2019). Blinatumomab/Lenalidomide in Relapsed/Refractory Non-Hodgkin's Lymphoma: A Phase I California Cancer Consortium Study of Safety, Efficacy and Immune Correlative Analysis. Blood. https://doi.org/10.1182/BLOOD-2019-124254

Van Der Sluis, I., De Lorenzo, P., Kotecha, R., Attarbaschi, A., Escherich, G., Nysom, K., Starý, J., Ferster, A., Brethon, B., Locatelli, F., Schrappe, M., Houtem, P., Valsecchi, M., & Pieters, R. (2023). Blinatumomab Added to Chemotherapy in Infant Lymphoblastic Leukemia.. The New England journal of medicine, 388 17, 1572-1581. https://doi.org/10.1056/NEJMoa2214171

Mocquot, P., Mossazadeh, Y., Lapierre, L., Pineau, F., & Despas, F. (2022). 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, 47, 1337 - 1351. https://doi.org/10.1111/jcpt.13741

Dufner, V., Sayehli, C., Chatterjee, M., Hummel, H., Gelbrich, G., Bargou, R., & Goebeler, M. (2019). Long-term outcome of patients with relapsed/refractory B-cell non-Hodgkin lymphoma treated with blinatumomab.. Blood advances, 3 16, 2491-2498. https://doi.org/10.1182/bloodadvances.2019000025

(2022). Blinatumomab. Reactions Weekly, 1906, 117 - 117. https://doi.org/10.1007/s40278-022-15007-y

Topp, M., Kufer, P., Gökbuget, N., Goebeler, M., Klinger, M., Neumann, S., Horst, H., Raff, T., Viardot, A., Schmid, M., Stelljes, M., Schaich, M., Degenhard, E., Köhne-Volland, R., Brüggemann, M., Ottmann, O., Pfeifer, H., Burmeister, T., Nagorsen, D., Schmidt, M., Lutterbuese, R., Reinhardt, C., Baeuerle, P., Kneba, M., Einsele, H., Riethmüller, G., Hoelzer, D., Zugmaier, G., & Bargou, R. (2011). Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival.. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 29 18, 2493-8. https://doi.org/10.1200/JCO.2010.32.7270

Nägele, V., Kratzer, A., Zugmaier, G., Holland, C., Hijazi, Y., Topp, M., Gökbuget, N., Baeuerle, P., Kufer, P., Wolf, A., & Klinger, M. (2017). Changes in clinical laboratory parameters and pharmacodynamic markers in response to blinatumomab treatment of patients with relapsed/refractory ALL. Experimental Hematology & Oncology, 6. https://doi.org/10.1186/s40164-017-0074-5

Hogan, L., Brown, P., Ji, L., Xu, X., Devidas, M., Bhatla, T., Borowitz, M., Raetz, E., Carroll, A., Heerema, N., Zugmaier, G., Sharon, E., Bernhardt, M., Terezakis, S., Gore, L., Whitlock, J., Hunger, S., & Loh, M. (2023). Children's Oncology Group AALL1331: Phase III Trial of Blinatumomab in Children, Adolescents, and Young Adults With Low-Risk B-Cell ALL in First Relapse. Journal of Clinical Oncology, 41, 4118 - 4129. https://doi.org/10.1200/JCO.22.02200

Burt, R., Warcel, D., & Fielding, A. (2018). Blinatumomab, a bispecific B-cell and T-cell engaging antibody, in the treatment of B-cell malignancies. Human Vaccines & Immunotherapeutics, 15, 594 - 602. https://doi.org/10.1080/21645515.2018.1540828

Lantz, J., Pham, N., Jones, C., Reed, D., Chaer, F., & Keng, M. (2023). Blinatumomab in Practice. Current Hematologic Malignancy Reports, 19, 1-8. https://doi.org/10.1007/s11899-023-00714-7

Gökbuget, N., Dombret, H., Bonifacio, M., Reichle, A., Graux, C., Faul, C., Diedrich, H., Topp, M., Brüggemann, M., Horst, H., Havelange, V., Stieglmaier, J., Wessels, H., Haddad, V., Benjamin, J., Zugmaier, G., Nagorsen, D., & Bargou, R. (2018). Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia.. Blood, 131 14, 1522-1531. https://doi.org/10.1182/blood-2017-08-798322