Blinatumomab as postremission therapy replaces consolidation and substantial parts of maintenance chemotherapy and results in stable MRD negativity in children with newly diagnosed B-lineage ALL
The bispecific T cell-binding antibody blinatumomab (CD19/CD3) is widely and successfully used for the treatment of children with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Here, we report the efficacy of a single course of blinatumomab instead of consolidation c...
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BMJ Publishing Group
2024-06-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/6/e008213.full |
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| author | Guenter Henze Ekaterina Mikhailova Alexander Popov Julia Roumiantseva Oleg Budanov Svetlana Lagoyko Liudmila Zharikova Natalia Miakova Dmitry Litvinov Lili Khachatryan Alexey Pshonkin Natalia Ponomareva Elmira Boichenko Svetlana Varfolomeeva Julia Dinikina Galina Novichkova Alexander Karachunskiy |
| author_facet | Guenter Henze Ekaterina Mikhailova Alexander Popov Julia Roumiantseva Oleg Budanov Svetlana Lagoyko Liudmila Zharikova Natalia Miakova Dmitry Litvinov Lili Khachatryan Alexey Pshonkin Natalia Ponomareva Elmira Boichenko Svetlana Varfolomeeva Julia Dinikina Galina Novichkova Alexander Karachunskiy |
| author_sort | Guenter Henze |
| collection | DOAJ |
| description | The bispecific T cell-binding antibody blinatumomab (CD19/CD3) is widely and successfully used for the treatment of children with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Here, we report the efficacy of a single course of blinatumomab instead of consolidation chemotherapy to eliminate minimal residual disease (MRD) and maintain stable MRD-negativity in children with primary BCP-ALL.Between February 2020 and November 2022, 177 children with non-high-risk BCP-ALL were enrolled in the ALL-MB 2019 pilot study (NCT04723342). Patients received the usual risk-adapted induction therapy according to the ALL-MB 2015 protocol. Those who achieved a complete remission at the end of induction (EOI) received treatment with blinatumomab immediately after induction at a dose of 5 μg/m2/day for 7 days and 21 days at a dose of 15 μg/m2/day, followed by 12 months of maintenance therapy. MRD was measured using multicolor flow cytometry (MFC) at the EOI, then immediately after blinatumomab treatment, and then four times during maintenance therapy at 3-month intervals.All 177 patients successfully completed induction therapy and achieved a complete hematological remission. In 174 of these, MFC-MRD was measured at the EOI. 143 patients (82.2%) were MFC-MRD negative and the remaining 31 patients had varying degrees of MFC-MRD positivity.MFC-MRD was assessed in all 176 patients who completed the blinatumomab course. With one exception, all patients achieved MFC-MRD negativity after blinatumomab, regardless of the MFC-MRD score at EOI. One adolescent girl with high MFC-MRD positivity at EOI remained MFC-MRD positive. Of 175 patients who had completed 6 months of maintenance therapy, MFC-MRD data were available for 156 children. Of these, 155 (99.4%) were MFC-MRD negative. Only one boy with t(12;21) (p13;q22)/ETV6::RUNX1 became MFC-MRD positive again. The remaining 174 children had completed the entire therapy. MFC-MRD was examined in 154 of them, and 153 were MFC-MRD negative. A girl with hypodiploid BCP-ALL showed a reappearance of MFC-MRD with subsequent relapse.In summary, a single 28-day course of blinatumomab immediately after induction, followed by 12 months of maintenance therapy, is highly effective in achieving MRD-negativity in children with newly diagnosed non-high risk BCP-ALL and maintaining MRD-negative remission at least during the treatment period. |
| format | Article |
| id | doaj-art-df13223cf72b4f50af1be617fa311e73 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-06-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-df13223cf72b4f50af1be617fa311e732025-08-20T01:51:48ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-06-0112610.1136/jitc-2023-008213Blinatumomab as postremission therapy replaces consolidation and substantial parts of maintenance chemotherapy and results in stable MRD negativity in children with newly diagnosed B-lineage ALLGuenter Henze0Ekaterina Mikhailova1Alexander Popov2Julia Roumiantseva3Oleg Budanov4Svetlana Lagoyko5Liudmila Zharikova6Natalia Miakova7Dmitry Litvinov8Lili Khachatryan9Alexey Pshonkin10Natalia Ponomareva11Elmira Boichenko12Svetlana Varfolomeeva13Julia Dinikina14Galina Novichkova15Alexander Karachunskiy16Pediatric Hematology and Oncology, Charite Medical Faculty Berlin, Berlin, Berlin, GermanyDmitry Rogachev National Medical Research Center of Pediatric Hematology Oncology and Immunology, Moscow, Russian FederationDmitry Rogachev National Medical Research Center of Pediatric Hematology Oncology and Immunology, Moscow, Russian FederationDmitry Rogachev National Medical Research Center of Pediatric Hematology Oncology and Immunology, Moscow, Russian FederationDmitry Rogachev National Medical Research Center of Pediatric Hematology Oncology and Immunology, Moscow, Russian FederationDmitry Rogachev National Medical Research Center of Pediatric Hematology Oncology and Immunology, Moscow, Russian FederationDmitry Rogachev National Medical Research Center of Pediatric Hematology Oncology and Immunology, Moscow, Russian FederationDmitry Rogachev National Medical Research Center of Pediatric Hematology Oncology and Immunology, Moscow, Russian FederationDmitry Rogachev National Medical Research Center of Pediatric Hematology Oncology and Immunology, Moscow, Russian FederationDmitry Rogachev National Medical Research Center of Pediatric Hematology Oncology and Immunology, Moscow, Russian FederationDmitry Rogachev National Medical Research Center of Pediatric Hematology Oncology and Immunology, Moscow, Russian FederationRussian Children Clinical Hospital, Moscow, Russian FederationCity Children’s Hospital No 1, Saint Petersburg, Russian FederationNN Blokhin National Medical Research Center of Oncology, Moscow, Russian FederationAlmazov National Medical Research Center, Saint Petersburg, Russian FederationDmitry Rogachev National Medical Research Center of Pediatric Hematology Oncology and Immunology, Moscow, Russian FederationDmitry Rogachev National Medical Research Center of Pediatric Hematology Oncology and Immunology, Moscow, Russian FederationThe bispecific T cell-binding antibody blinatumomab (CD19/CD3) is widely and successfully used for the treatment of children with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Here, we report the efficacy of a single course of blinatumomab instead of consolidation chemotherapy to eliminate minimal residual disease (MRD) and maintain stable MRD-negativity in children with primary BCP-ALL.Between February 2020 and November 2022, 177 children with non-high-risk BCP-ALL were enrolled in the ALL-MB 2019 pilot study (NCT04723342). Patients received the usual risk-adapted induction therapy according to the ALL-MB 2015 protocol. Those who achieved a complete remission at the end of induction (EOI) received treatment with blinatumomab immediately after induction at a dose of 5 μg/m2/day for 7 days and 21 days at a dose of 15 μg/m2/day, followed by 12 months of maintenance therapy. MRD was measured using multicolor flow cytometry (MFC) at the EOI, then immediately after blinatumomab treatment, and then four times during maintenance therapy at 3-month intervals.All 177 patients successfully completed induction therapy and achieved a complete hematological remission. In 174 of these, MFC-MRD was measured at the EOI. 143 patients (82.2%) were MFC-MRD negative and the remaining 31 patients had varying degrees of MFC-MRD positivity.MFC-MRD was assessed in all 176 patients who completed the blinatumomab course. With one exception, all patients achieved MFC-MRD negativity after blinatumomab, regardless of the MFC-MRD score at EOI. One adolescent girl with high MFC-MRD positivity at EOI remained MFC-MRD positive. Of 175 patients who had completed 6 months of maintenance therapy, MFC-MRD data were available for 156 children. Of these, 155 (99.4%) were MFC-MRD negative. Only one boy with t(12;21) (p13;q22)/ETV6::RUNX1 became MFC-MRD positive again. The remaining 174 children had completed the entire therapy. MFC-MRD was examined in 154 of them, and 153 were MFC-MRD negative. A girl with hypodiploid BCP-ALL showed a reappearance of MFC-MRD with subsequent relapse.In summary, a single 28-day course of blinatumomab immediately after induction, followed by 12 months of maintenance therapy, is highly effective in achieving MRD-negativity in children with newly diagnosed non-high risk BCP-ALL and maintaining MRD-negative remission at least during the treatment period.https://jitc.bmj.com/content/12/6/e008213.full |
| spellingShingle | Guenter Henze Ekaterina Mikhailova Alexander Popov Julia Roumiantseva Oleg Budanov Svetlana Lagoyko Liudmila Zharikova Natalia Miakova Dmitry Litvinov Lili Khachatryan Alexey Pshonkin Natalia Ponomareva Elmira Boichenko Svetlana Varfolomeeva Julia Dinikina Galina Novichkova Alexander Karachunskiy Blinatumomab as postremission therapy replaces consolidation and substantial parts of maintenance chemotherapy and results in stable MRD negativity in children with newly diagnosed B-lineage ALL Journal for ImmunoTherapy of Cancer |
| title | Blinatumomab as postremission therapy replaces consolidation and substantial parts of maintenance chemotherapy and results in stable MRD negativity in children with newly diagnosed B-lineage ALL |
| title_full | Blinatumomab as postremission therapy replaces consolidation and substantial parts of maintenance chemotherapy and results in stable MRD negativity in children with newly diagnosed B-lineage ALL |
| title_fullStr | Blinatumomab as postremission therapy replaces consolidation and substantial parts of maintenance chemotherapy and results in stable MRD negativity in children with newly diagnosed B-lineage ALL |
| title_full_unstemmed | Blinatumomab as postremission therapy replaces consolidation and substantial parts of maintenance chemotherapy and results in stable MRD negativity in children with newly diagnosed B-lineage ALL |
| title_short | Blinatumomab as postremission therapy replaces consolidation and substantial parts of maintenance chemotherapy and results in stable MRD negativity in children with newly diagnosed B-lineage ALL |
| title_sort | blinatumomab as postremission therapy replaces consolidation and substantial parts of maintenance chemotherapy and results in stable mrd negativity in children with newly diagnosed b lineage all |
| url | https://jitc.bmj.com/content/12/6/e008213.full |
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