Inotuzumab ozogamicin (InO) for relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) in the phase III INO-VATE trial: Efficacy and safety by prior therapy

Background:InO, an anti-CD22 antibody-calicheamicin conjugate, showed superior response vs standard care for R/R ALL in the phase III INO-VATE trial. Herein, effects of prior therapy on response and toxicities were assessed in patients (pts) receiving InO. 


Methods:Per protocol, intent-to-treat analyses of complete remission [CR]/CR with incomplete hematologic recovery [CRi] included the first 218 of 326 pts randomized (ITT218). The safety population included 139 pts who received ≥ 1 InO dose (max 1.8 mg/m2/cycle [0.8 mg/m2 on d1; 0.5 mg/m2 on d8 and 15 of a 21–28 d cycle for ≤ 6 cycles]). Minimal residual disease (MRD) negativity was assessed by central flow cytometry ( < 0.01%). Data as of October 2, 2014 are presented (trial ongoing). 


Results:109 pts in the ITT218 received InO (CR/CRi rate, 81% [95% CI, 72–88]; MRD negativity rate in responders, 78% [95% CI, 68–87]; median remission duration [DoR], 4.6 [95% CI, 3.9–5.4] mo). 67% and 32% of pts received InO as salvage (S) 1 and S2 (missing, n = 1). For S1 vs S2, response was numerically higher, MRD-negativity was similar, and DoR was numerically longer (Table). CR/CRi rate was numerically lower for pts with (n = 17) vs without (w/o) (n = 92) prior SCT (77% [95% CI, 50–93] vs 82% [72–89]). In the safety population, Gr ≥ 3 febrile neutropenia rates were similar for S1 (n = 95) vs S2 (n = 43) (both 23%) and for pts with (n = 24) vs w/o (n = 115) prior SCT (29% vs 23%). Any grade hepatobiliary AE rates were significantly higher in S2 vs S1 (47% vs 17%; P< 0.001) and numerically higher for pts with vs w/o prior SCT (42% vs 23%). For S1 vs S2, 36 vs 11 pts had poststudy SCT. Veno-occlusive liver disease (VOD) including post-SCT VOD occurred in 8% of S1 vs 16% of S2 pts (2 fatal in S1); in 21% with vs 9% w/o prior SCT (1 fatal in each cohort). 


Conclusions:InO may provide clinical benefit in pts with R/R ALL for both S1 and S2 therapy; hepatotoxicity risk increases with number of prior therapies and prior SCT. Clinical trial information: NCT01564784


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