INOTUZUMAB OZOGAMICIN FOR RELAPSED/REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA IN THE GLOBAL PHASE 3 RANDOMIZED CONTROLLED INO-VATE TRIAL: EFFICACY AND SAFETY BY PRIOR THERAPY
(Abstract release date: 05/19/16)
EHA Library. DeAngelo D. 06/11/16; 135255; S499
Daniel J DeAngelo
Contributions
Contributions
Abstract
Abstract: S499
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:45 - 17:00
Location: Auditorium 2
Background
Inotuzumab Ozogamicin (InO), an anti-CD22 antibody-calicheamicin conjugate, showed superior response vs standard care for relapsed/refractory acute lymphoblastic leukemia (ALL) in the ongoing phase 3 INO-VATE trial.
Aims
To assess the effects of prior therapy on response and toxicities in patients with relapsed/refractory ALL receiving InO in the phase 3 trial
Methods
Per protocol, intent-to-treat analyses of complete remission [CR]/CR with incomplete hematologic recovery [CRi] included the first 218 of 326 patients randomized (ITT218). The safety population included 139 patients who received ≥1 InO dose (max 1.8 mg/m2/cycle [0.8 mg/m2 on day 1; 0.5 mg/m2 on days 8 and 15 of a 21–28 day 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). Informed consent was obtained from all patients.
Results
109 patients 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] months). 67% and 32% of patients 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 patients with (n=17) vs without (n=92) prior SCT (77% [95% CI, 50–93] vs 82% [72–89]). In the safety population, grade ≥3 febrile neutropenia rates were similar for S1 (n=95) vs S2 (n=43) (both 23%) and for patients with (n=24) vs without (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 patients with vs without prior SCT (42% vs 23%). For S1 vs S2, 36 vs 11 patients had poststudy SCT. Veno-occlusive liver disease (VOD) including post-SCT VOD occurred in 8% of S1 vs 16% of S2 patients (2 fatal in S1); in 21% with vs 9% without prior SCT (1 fatal in each cohort).
Conclusion
InO may provide clinical benefit in patients with relapsed/refractory ALL for both S1 and S2 therapy; hepatotoxicity risk increases with number of prior therapies and prior SCT.
Session topic: Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia, Chemotherapy, Phase III, Relapsed acute lymphoblastic leukemia
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:45 - 17:00
Location: Auditorium 2
Background
Inotuzumab Ozogamicin (InO), an anti-CD22 antibody-calicheamicin conjugate, showed superior response vs standard care for relapsed/refractory acute lymphoblastic leukemia (ALL) in the ongoing phase 3 INO-VATE trial.
Aims
To assess the effects of prior therapy on response and toxicities in patients with relapsed/refractory ALL receiving InO in the phase 3 trial
Methods
Per protocol, intent-to-treat analyses of complete remission [CR]/CR with incomplete hematologic recovery [CRi] included the first 218 of 326 patients randomized (ITT218). The safety population included 139 patients who received ≥1 InO dose (max 1.8 mg/m2/cycle [0.8 mg/m2 on day 1; 0.5 mg/m2 on days 8 and 15 of a 21–28 day 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). Informed consent was obtained from all patients.
Results
109 patients 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] months). 67% and 32% of patients 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 patients with (n=17) vs without (n=92) prior SCT (77% [95% CI, 50–93] vs 82% [72–89]). In the safety population, grade ≥3 febrile neutropenia rates were similar for S1 (n=95) vs S2 (n=43) (both 23%) and for patients with (n=24) vs without (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 patients with vs without prior SCT (42% vs 23%). For S1 vs S2, 36 vs 11 patients had poststudy SCT. Veno-occlusive liver disease (VOD) including post-SCT VOD occurred in 8% of S1 vs 16% of S2 patients (2 fatal in S1); in 21% with vs 9% without prior SCT (1 fatal in each cohort).
Conclusion
InO may provide clinical benefit in patients with relapsed/refractory ALL for both S1 and S2 therapy; hepatotoxicity risk increases with number of prior therapies and prior SCT.
Session topic: Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia, Chemotherapy, Phase III, Relapsed acute lymphoblastic leukemia
Abstract: S499
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:45 - 17:00
Location: Auditorium 2
Background
Inotuzumab Ozogamicin (InO), an anti-CD22 antibody-calicheamicin conjugate, showed superior response vs standard care for relapsed/refractory acute lymphoblastic leukemia (ALL) in the ongoing phase 3 INO-VATE trial.
Aims
To assess the effects of prior therapy on response and toxicities in patients with relapsed/refractory ALL receiving InO in the phase 3 trial
Methods
Per protocol, intent-to-treat analyses of complete remission [CR]/CR with incomplete hematologic recovery [CRi] included the first 218 of 326 patients randomized (ITT218). The safety population included 139 patients who received ≥1 InO dose (max 1.8 mg/m2/cycle [0.8 mg/m2 on day 1; 0.5 mg/m2 on days 8 and 15 of a 21–28 day 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). Informed consent was obtained from all patients.
Results
109 patients 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] months). 67% and 32% of patients 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 patients with (n=17) vs without (n=92) prior SCT (77% [95% CI, 50–93] vs 82% [72–89]). In the safety population, grade ≥3 febrile neutropenia rates were similar for S1 (n=95) vs S2 (n=43) (both 23%) and for patients with (n=24) vs without (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 patients with vs without prior SCT (42% vs 23%). For S1 vs S2, 36 vs 11 patients had poststudy SCT. Veno-occlusive liver disease (VOD) including post-SCT VOD occurred in 8% of S1 vs 16% of S2 patients (2 fatal in S1); in 21% with vs 9% without prior SCT (1 fatal in each cohort).
Conclusion
InO may provide clinical benefit in patients with relapsed/refractory ALL for both S1 and S2 therapy; hepatotoxicity risk increases with number of prior therapies and prior SCT.
Session topic: Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia, Chemotherapy, Phase III, Relapsed acute lymphoblastic leukemia
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:45 - 17:00
Location: Auditorium 2
Background
Inotuzumab Ozogamicin (InO), an anti-CD22 antibody-calicheamicin conjugate, showed superior response vs standard care for relapsed/refractory acute lymphoblastic leukemia (ALL) in the ongoing phase 3 INO-VATE trial.
Aims
To assess the effects of prior therapy on response and toxicities in patients with relapsed/refractory ALL receiving InO in the phase 3 trial
Methods
Per protocol, intent-to-treat analyses of complete remission [CR]/CR with incomplete hematologic recovery [CRi] included the first 218 of 326 patients randomized (ITT218). The safety population included 139 patients who received ≥1 InO dose (max 1.8 mg/m2/cycle [0.8 mg/m2 on day 1; 0.5 mg/m2 on days 8 and 15 of a 21–28 day 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). Informed consent was obtained from all patients.
Results
109 patients 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] months). 67% and 32% of patients 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 patients with (n=17) vs without (n=92) prior SCT (77% [95% CI, 50–93] vs 82% [72–89]). In the safety population, grade ≥3 febrile neutropenia rates were similar for S1 (n=95) vs S2 (n=43) (both 23%) and for patients with (n=24) vs without (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 patients with vs without prior SCT (42% vs 23%). For S1 vs S2, 36 vs 11 patients had poststudy SCT. Veno-occlusive liver disease (VOD) including post-SCT VOD occurred in 8% of S1 vs 16% of S2 patients (2 fatal in S1); in 21% with vs 9% without prior SCT (1 fatal in each cohort).
Conclusion
InO may provide clinical benefit in patients with relapsed/refractory ALL for both S1 and S2 therapy; hepatotoxicity risk increases with number of prior therapies and prior SCT.
Session topic: Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia, Chemotherapy, Phase III, Relapsed acute lymphoblastic leukemia
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