TY - JOUR
T1 - Time to First Subsequent Salvage Therapy in Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia Treated With Inotuzumab Ozogamicin in the Phase III INO-VATE Trial
AU - Stelljes, Matthias
AU - Advani, Anjali S.
AU - DeAngelo, Daniel J.
AU - Wang, Tao
AU - Neuhof, Alexander
AU - Vandendries, Erik
AU - Kantarjian, Hagop
AU - Jabbour, Elias
N1 - Funding Information:
MS declares research support and honoraria from Pfizer. ASA declares consulting fees and honoraria from Pfizer, research funding from Amgen and AbbVie, and honoraria from Kite Pharma. DJD declares honoraria from Amgen, Autolos, Agios, Blueprint Pharmaceuticals, Forty-Seven, Incyte, Jazz Pharmaceuticals, Kite Pharma, Novartis, Pfizer, Shire, and Takeda; and research funding from AbbVie, Gylcomimetics, Novartis, and Blueprint Pharmaceuticals. TW, AN, and EV are employees of and own stock in Pfizer. HK declares honoraria and research grants from AbbVie, Amgen, Daiichi-Sankyo, and Pfizer; grants from Ascentage, Bristol-Myers Squibb, Immunogen, Jazz Pharmaceuticals, and Sanofi; honoraria from Bio Ascend, Novartis, Takeda, Adaptive Biotechnologies, Aptitude Health, Delta Fly, Janssen Global, and Oxford Biomedical; and has served on an advisory board for Actinium. EJ has received research grants and consultancy fees from Amgen, Pfizer, Takeda, Adaptive Biotechnologies, AbbVie, Bristol-Myers Squibb, Spectrum, and Genentech.
Publisher Copyright:
© 2022 The Authors
PY - 2022/9
Y1 - 2022/9
N2 - Background: In relapsed/refractory acute lymphoblastic leukemia (R/R ALL), successive salvage therapies may worsen outcomes and decrease quality of life. This post hoc analysis of the phase III INO-VATE trial investigates subsequent salvage therapies and compared the time from randomization to first subsequent salvage therapy (TST) in the inotuzumab ozogamicin (InO) and standard-of-care chemotherapy (SoC) arms. Patients and Methods: Adults (aged ≥18 years) with CD22+ R/R ALL were randomized to InO (n = 164) or SoC (n = 162) treatment. We determined TST and proportion of patients receiving subsequent salvage therapies by treatment arm and for subgroups based on transplantation status and baseline characteristics. Results: In the InO versus SoC arm, a smaller proportion of patients received subsequent salvage therapy (34.1% [n = 56] vs. 56.8% [n = 92]), and TST was longer (median 19 vs. 4 months, hazard ratio 0.339, P < .0001). Similar benefits were seen with InO versus SoC irrespective of transplantation status, age, salvage phase, first remission duration, Philadelphia chromosome status, or CD22 expression. Following receipt of subsequent salvage therapy, median overall survival was 4 months, irrespective of treatment arm. Conclusion: Patients in the InO versus SoC arm were less likely to receive subsequent salvage therapy, and showed a clinically meaningful extension of TST irrespective of subgroup. This suggests InO treatment leads to improved outcomes by increasing the likelihood that subsequent salvage therapies and their associated adverse impacts can be delayed or avoided. Plain language summary: Available in Supplementary Materials. Clinical Trial Registration: NCT01564784.
AB - Background: In relapsed/refractory acute lymphoblastic leukemia (R/R ALL), successive salvage therapies may worsen outcomes and decrease quality of life. This post hoc analysis of the phase III INO-VATE trial investigates subsequent salvage therapies and compared the time from randomization to first subsequent salvage therapy (TST) in the inotuzumab ozogamicin (InO) and standard-of-care chemotherapy (SoC) arms. Patients and Methods: Adults (aged ≥18 years) with CD22+ R/R ALL were randomized to InO (n = 164) or SoC (n = 162) treatment. We determined TST and proportion of patients receiving subsequent salvage therapies by treatment arm and for subgroups based on transplantation status and baseline characteristics. Results: In the InO versus SoC arm, a smaller proportion of patients received subsequent salvage therapy (34.1% [n = 56] vs. 56.8% [n = 92]), and TST was longer (median 19 vs. 4 months, hazard ratio 0.339, P < .0001). Similar benefits were seen with InO versus SoC irrespective of transplantation status, age, salvage phase, first remission duration, Philadelphia chromosome status, or CD22 expression. Following receipt of subsequent salvage therapy, median overall survival was 4 months, irrespective of treatment arm. Conclusion: Patients in the InO versus SoC arm were less likely to receive subsequent salvage therapy, and showed a clinically meaningful extension of TST irrespective of subgroup. This suggests InO treatment leads to improved outcomes by increasing the likelihood that subsequent salvage therapies and their associated adverse impacts can be delayed or avoided. Plain language summary: Available in Supplementary Materials. Clinical Trial Registration: NCT01564784.
KW - ALL
KW - Inotuzumab ozogamicin
KW - TST
KW - TTNT
KW - Time to next treatment
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U2 - 10.1016/j.clml.2022.04.022
DO - 10.1016/j.clml.2022.04.022
M3 - Article
C2 - 35643855
AN - SCOPUS:85131101248
SN - 2152-2650
VL - 22
SP - e836-e843
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 9
ER -