TY - JOUR
T1 - Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia
T2 - Final report and long-term survival follow-up from the randomized, phase 3 INO-VATE study
AU - Kantarjian, Hagop M.
AU - DeAngelo, Daniel J.
AU - Stelljes, Matthias
AU - Liedtke, Michaela
AU - Stock, Wendy
AU - Gökbuget, Nicola
AU - O’Brien, Susan M.
AU - Jabbour, Elias
AU - Wang, Tao
AU - Liang White, Jane
AU - Sleight, Barbara
AU - Vandendries, Erik
AU - Advani, Anjali S.
N1 - Publisher Copyright:
© 2019 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society
PY - 2019/7/15
Y1 - 2019/7/15
N2 - Background: Inotuzumab ozogamicin (InO) is an antibody-drug conjugate used for adults with relapsed/refractory B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The INotuzumab Ozogamicin trial to inVestigAte Tolerability and Efficacy (INO-VATE) previously reported improved outcomes with InO versus standard-of-care (SoC) chemotherapy. This article reports the final INO-VATE results (≥2 years of follow-up) and additional analyses of patient characteristics associated with improved outcomes. Methods: Between August 27, 2012, and January 4, 2015, this multicenter, parallel, open-label, phase 3 trial randomized 326 adults with relapsed/refractory ALL to InO (n = 164) or SoC (n = 162); 307 received 1 or more doses of the study drug (164 in the InO arm and 143 in the SoC arm). Results: The complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) rate was higher with InO versus SoC (73.8% vs 30.9%; 1-sided P <.0001), with consistent CR/CRi rates across patient subgroups. The median overall survival (OS) was 7.7 months with InO and 6.2 months with SoC, with 2-year OS rates of 22.8% and 10.0%, respectively (overall hazard ratio, 0.75; 97.5% confidence interval [CI], 0.57-0.99; 1-sided P =.0105). The predictors of OS with InO were the best minimal residual disease status, baseline platelet count, duration of first remission, achievement of CR/CRi, and follow-up hematopoietic stem cell transplantation (HSCT; all 2-sided P values <.05). More InO arm patients proceeded directly to HSCT after achieving CR/CRi before any follow-up induction therapy (39.6% [95% CI, 32.1%-47.6%] vs 10.5% [6.2%-16.3%]; 1-sided P <.0001). The most frequent all-grade and grade 3 or higher adverse events in both arms were hematologic. Veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) was more frequent with InO (23 of 164 [14.0%] vs 3 of 143 [2.1%]). Conclusions: In patients with relapsed/refractory BCP ALL in INO-VATE, InO was associated with a greater likelihood of CR/CRi across key patient subgroups, and it served as a bridge to HSCT. Potential VOD/SOS risk factors must be considered when InO treatment decisions are being made.
AB - Background: Inotuzumab ozogamicin (InO) is an antibody-drug conjugate used for adults with relapsed/refractory B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The INotuzumab Ozogamicin trial to inVestigAte Tolerability and Efficacy (INO-VATE) previously reported improved outcomes with InO versus standard-of-care (SoC) chemotherapy. This article reports the final INO-VATE results (≥2 years of follow-up) and additional analyses of patient characteristics associated with improved outcomes. Methods: Between August 27, 2012, and January 4, 2015, this multicenter, parallel, open-label, phase 3 trial randomized 326 adults with relapsed/refractory ALL to InO (n = 164) or SoC (n = 162); 307 received 1 or more doses of the study drug (164 in the InO arm and 143 in the SoC arm). Results: The complete remission (CR)/complete remission with incomplete hematologic recovery (CRi) rate was higher with InO versus SoC (73.8% vs 30.9%; 1-sided P <.0001), with consistent CR/CRi rates across patient subgroups. The median overall survival (OS) was 7.7 months with InO and 6.2 months with SoC, with 2-year OS rates of 22.8% and 10.0%, respectively (overall hazard ratio, 0.75; 97.5% confidence interval [CI], 0.57-0.99; 1-sided P =.0105). The predictors of OS with InO were the best minimal residual disease status, baseline platelet count, duration of first remission, achievement of CR/CRi, and follow-up hematopoietic stem cell transplantation (HSCT; all 2-sided P values <.05). More InO arm patients proceeded directly to HSCT after achieving CR/CRi before any follow-up induction therapy (39.6% [95% CI, 32.1%-47.6%] vs 10.5% [6.2%-16.3%]; 1-sided P <.0001). The most frequent all-grade and grade 3 or higher adverse events in both arms were hematologic. Veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) was more frequent with InO (23 of 164 [14.0%] vs 3 of 143 [2.1%]). Conclusions: In patients with relapsed/refractory BCP ALL in INO-VATE, InO was associated with a greater likelihood of CR/CRi across key patient subgroups, and it served as a bridge to HSCT. Potential VOD/SOS risk factors must be considered when InO treatment decisions are being made.
KW - acute lymphoblastic leukemia
KW - adults
KW - hematopoietic stem cell transplantation
KW - hepatic veno-occlusive disease
KW - inotuzumab ozogamicin
KW - remission induction
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U2 - 10.1002/cncr.32116
DO - 10.1002/cncr.32116
M3 - Article
C2 - 30920645
AN - SCOPUS:85063585100
SN - 0008-543X
VL - 125
SP - 2474
EP - 2487
JO - Cancer
JF - Cancer
IS - 14
ER -