Efficacy and safety of currently approved and lower starting doses of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukemia: a phase IV study
Inotuzumab ozogamicin (InO) is approved for treatment of relapsed/refractory acute lymphoblastic leukemia (R/R ALL). Previous studies reported higher rates of post– hematopoietic stem cell transplant (HSCT) hepatic sinusoidal obstruction syndrome (SOS) in patients receiving InO versus chemotherapy...
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| Format: | Article |
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Ferrata Storti Foundation
2025-01-01
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| Series: | Haematologica |
| Online Access: | https://haematologica.org/article/view/11921 |
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| author | Muhit Özcan Ryan D. Cassaday Ewa Zarzycka Erik Vandendries Fan Zhang Ying Chen Alejandra Nieto Fatih Demirkan Pau Montesinos Fevzi Altuntas |
| author_facet | Muhit Özcan Ryan D. Cassaday Ewa Zarzycka Erik Vandendries Fan Zhang Ying Chen Alejandra Nieto Fatih Demirkan Pau Montesinos Fevzi Altuntas |
| author_sort | Muhit Özcan |
| collection | DOAJ |
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Inotuzumab ozogamicin (InO) is approved for treatment of relapsed/refractory acute lymphoblastic leukemia (R/R ALL). Previous studies reported higher rates of post– hematopoietic stem cell transplant (HSCT) hepatic sinusoidal obstruction syndrome (SOS) in patients receiving InO versus chemotherapy prior to HSCT. It is unknown if a lower InO dose would reduce risk of post-HSCT SOS or if it would impact efficacy. This study evaluated efficacy and safety of the currently approved InO starting dose and a lower dose in adults with R/R ALL who were eligible for HSCT and were identified as being at higher risk of post- HSCT SOS.
This open-label, phase 4 study (NCT03677596) had 2 phases: in the run-in phase patients received InO at 1.2 mg/m2/cycle (n=22); in the randomized phase patients received InO starting at dose levels of 1.8 mg/m2/cycle (n=38) or 1.2 mg/m2/cycle (n=42). Primary endpoints were rate of SOS and rate of hematologic remission.
Overall, SOS was reported in 10 patients (9.8%); all were post-HSCT SOS. In patients who proceeded to HSCT, post-HSCT SOS rates were 20%, 28.6%, 25.8%, and 16.7% in 1.2 mg/m2/cycle (run-in), 1.2 mg/m2/cycle (randomized), 1.2 mg/m2/cycle (run-in and randomized), and 1.8 mg/m2/cycle (randomized), respectively. The CR/CRi rates were 50.0%, 83.3%, 71.9%, and 68.4% in the respective subgroups.
The study found that a starting dose of 1.2mg/m2/cycle demonstrated consistent efficacy and safety to the recommended 1.8 mg/m2/cycle dose in adults with R/R ALL who were eligible for HSCT and had a higher risk of post-HSCT SOS.
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| format | Article |
| id | doaj-art-05b0e113557949d5a37432afceb33752 |
| institution | Kabale University |
| issn | 0390-6078 1592-8721 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Ferrata Storti Foundation |
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| series | Haematologica |
| spelling | doaj-art-05b0e113557949d5a37432afceb337522025-01-30T19:44:25ZengFerrata Storti FoundationHaematologica0390-60781592-87212025-01-01999110.3324/haematol.2024.286091Efficacy and safety of currently approved and lower starting doses of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukemia: a phase IV studyMuhit Özcan0Ryan D. Cassaday1Ewa Zarzycka2Erik Vandendries3Fan Zhang4Ying Chen5Alejandra Nieto6Fatih Demirkan7Pau Montesinos8Fevzi Altuntas9Ankara University School of Medicine, AnkaraUniversity of Washington and Fred Hutchinson Cancer Center, Seattle, WADepartment of Hematology and Transplantology, Medical University of Gdańsk, GdańskPfizer Inc, Cambridge, MAPfizer Inc, ShanghaiPfizer Inc., La Jolla, CAPfizer Inc, New York, NYDepartment of Hematology, Dokuz Eylul University, IzmirHematology Department, La Fe University and Polytechnic Hospital, ValenciaDr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara Inotuzumab ozogamicin (InO) is approved for treatment of relapsed/refractory acute lymphoblastic leukemia (R/R ALL). Previous studies reported higher rates of post– hematopoietic stem cell transplant (HSCT) hepatic sinusoidal obstruction syndrome (SOS) in patients receiving InO versus chemotherapy prior to HSCT. It is unknown if a lower InO dose would reduce risk of post-HSCT SOS or if it would impact efficacy. This study evaluated efficacy and safety of the currently approved InO starting dose and a lower dose in adults with R/R ALL who were eligible for HSCT and were identified as being at higher risk of post- HSCT SOS. This open-label, phase 4 study (NCT03677596) had 2 phases: in the run-in phase patients received InO at 1.2 mg/m2/cycle (n=22); in the randomized phase patients received InO starting at dose levels of 1.8 mg/m2/cycle (n=38) or 1.2 mg/m2/cycle (n=42). Primary endpoints were rate of SOS and rate of hematologic remission. Overall, SOS was reported in 10 patients (9.8%); all were post-HSCT SOS. In patients who proceeded to HSCT, post-HSCT SOS rates were 20%, 28.6%, 25.8%, and 16.7% in 1.2 mg/m2/cycle (run-in), 1.2 mg/m2/cycle (randomized), 1.2 mg/m2/cycle (run-in and randomized), and 1.8 mg/m2/cycle (randomized), respectively. The CR/CRi rates were 50.0%, 83.3%, 71.9%, and 68.4% in the respective subgroups. The study found that a starting dose of 1.2mg/m2/cycle demonstrated consistent efficacy and safety to the recommended 1.8 mg/m2/cycle dose in adults with R/R ALL who were eligible for HSCT and had a higher risk of post-HSCT SOS. https://haematologica.org/article/view/11921 |
| spellingShingle | Muhit Özcan Ryan D. Cassaday Ewa Zarzycka Erik Vandendries Fan Zhang Ying Chen Alejandra Nieto Fatih Demirkan Pau Montesinos Fevzi Altuntas Efficacy and safety of currently approved and lower starting doses of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukemia: a phase IV study Haematologica |
| title | Efficacy and safety of currently approved and lower starting doses of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukemia: a phase IV study |
| title_full | Efficacy and safety of currently approved and lower starting doses of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukemia: a phase IV study |
| title_fullStr | Efficacy and safety of currently approved and lower starting doses of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukemia: a phase IV study |
| title_full_unstemmed | Efficacy and safety of currently approved and lower starting doses of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukemia: a phase IV study |
| title_short | Efficacy and safety of currently approved and lower starting doses of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukemia: a phase IV study |
| title_sort | efficacy and safety of currently approved and lower starting doses of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukemia a phase iv study |
| url | https://haematologica.org/article/view/11921 |
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