TY - JOUR
T1 - Inotuzumab ozogamicin for relapsed/refractory acute lymphoblastic leukemia in the INO-VATE trial
T2 - CD22 pharmacodynamics, efficacy, and safety by baseline CD22
AU - Kantarjian, Hagop M.
AU - Stock, Wendy
AU - Cassaday, Ryan D.
AU - DeAngelo, Daniel J.
AU - Jabbour, Elias
AU - O’Brien, Susan M.
AU - Stelljes, Matthias
AU - Wang, Tao
AU - Luisa Paccagnella, M.
AU - Nguyen, Kevin
AU - Sleight, Barbara
AU - Vandendries, Erik
AU - Neuhof, Alexander
AU - Douglas Laird, A.
AU - Advani, Anjali S.
N1 - Funding Information:
This study was sponsored by Pfizer Inc. Medical writing support was provided by Shuang Li, PhD, of Engage Scientific Solutions and funded by Pfizer. Navigate BioPharma Services, Inc. were paid contractors to Pfizer Inc. for CD22 and MRD flow cytometry analyses and KMT2A assessment by FISH.
Funding Information:
H.M. Kantarjian reports grants and other from AbbVie, Amgen, Daiichi Sankyo, and Pfizer; grants from Ascentage, BMS, Immunogen, Jazz, and Sanofi; and other from Actinium, Adaptive Biotechnologies, Aptitude Health, Bio Ascend, Delta Fly, Jansen Global, Novartis, Biometical, and Takeda during the conduct of the study. W. Stock reports grants from Pfizer during the conduct of the study, other from Pfizer outside the submitted work, and speaking fees from Pfizer for educational conferences focused on care of ALL that have included discussion of inotuzumab ozogamicin. R.D. Cassaday reports grants and personal fees from Pfizer during the conduct of the study; grants and personal fees from Amgen and Kite/Gilead; grants outside the submitted work from Merck and Vanda Pharmaceuticals; and his spouse is employed by and owns stock in Seagen. D.J. DeAngelo reports other from AbbVie, GlycoMimetics, Novartis, and Blueprint Pharmaceuticals during the conduct of the study and personal fees from Amgen, Autolus, Agios, Blueprint, Forty-Seven, Incyte, Jazz, Kite, Novartis, Pfizer, Servier, and Takeda outside the submitted work. E. Jabbour reports grants and personal fees from Pfizer, Amgen, Takeda, AbbVie, and BMS and personal fees from Genentech outside the submitted work. S.M. O’Brien reports other from Celgene, GlaxoSmithKline, Janssen Oncology, Aptose Biosciences, Vaniam Group, AbbVie, Verastem, Vida Ventures, Autolus, Johnson & Johnson, Merck, Kite, Regeneron, Acerta, Gilead, Pharmacyclics, TG Therapeutics, Pfizer, and Sunesis outside the submitted work. M. Stelljes reports grants and personal fees from Pfizer and personal fees from Amgen during the conduct of the study. T. Wang, M.L. Paccagnella, B. Sleight, E. Vandendries, A. Neuhof, and A.D. Laird are employees of and have stock and/or other ownership interests in Pfizer. A.S. Advani reports grants and nonfinancial support from Pfizer during the conduct of the study; grants and other from Pfizer, Amgen, Seattle Genetics, and GlycoMimetics; other from Kite Pharmaceuticals; and grants from Immunogen, MacroGenics, AbbVie, and OBI Pharmaceuticals outside the submitted work. No disclosures were reported by the other authors.
Publisher Copyright:
© American Association for Cancer Research.
PY - 2021/5
Y1 - 2021/5
N2 - Purpose: We assessed the relationship between cluster of differentiation-22 (CD22) expression and outcomes of inotuzumab ozogamicin versus standard of care (SC) in INO-VATE (NCT01564784). Patients and Methods: Adults with relapsed/refractory B-cell precursor CD22-positive (by local or central laboratory) acute lymphoblastic leukemia were randomized to inotuzumab ozogamicin (n ¼ 164) or SC (n ¼ 162). Outcomes were analyzed by baseline CD22 positivity (percentage of leukemic blasts CD22 positive, ≥90% vs. <90%) and CD22 receptor density [molecules of equivalent soluble fluorochrome (MESF), quartile analysis]. Results: Most patients had high (≥90%) CD22 positivity per central laboratory. The response rate was significantly higher with inotuzumab ozogamicin versus SC. Minimal/measurable residual disease negativity, duration of remission (DoR), progression-free survival, and overall survival (OS) were significantly better with inotuzumab ozogamicin versus SC in patients with CD22 positivity ≥90%. Fewer patients had CD22 positivity <90%; for whom, response rates were higher with inotuzumab ozogamicin versus SC, but DoR and OS appeared similar. Similar trends were evident in quartile analyses of CD22 MESF and CD22 positivity per local laboratory. Among inotuzumab ozogamicin–responding patients with subsequent relapse, decrease in CD22 positivity and receptor density was evident, but not the emergence of CD22 negativity. Rates of grade ≥3 hematologic adverse events (AEs) were similar and hepatobiliary AEs rate was higher for inotuzumab ozogamicin versus SC. No apparent relationship was observed between the rates of hematologic and hepatic AEs and CD22 expression. Conclusions: Inotuzumab ozogamicin demonstrated a favorable benefit–risk profile versus SC in patients with higher and lower CD22 expression. Patients with high CD22 expression and normal cytogenetics benefited the most from inotuzumab ozogamicin therapy.
AB - Purpose: We assessed the relationship between cluster of differentiation-22 (CD22) expression and outcomes of inotuzumab ozogamicin versus standard of care (SC) in INO-VATE (NCT01564784). Patients and Methods: Adults with relapsed/refractory B-cell precursor CD22-positive (by local or central laboratory) acute lymphoblastic leukemia were randomized to inotuzumab ozogamicin (n ¼ 164) or SC (n ¼ 162). Outcomes were analyzed by baseline CD22 positivity (percentage of leukemic blasts CD22 positive, ≥90% vs. <90%) and CD22 receptor density [molecules of equivalent soluble fluorochrome (MESF), quartile analysis]. Results: Most patients had high (≥90%) CD22 positivity per central laboratory. The response rate was significantly higher with inotuzumab ozogamicin versus SC. Minimal/measurable residual disease negativity, duration of remission (DoR), progression-free survival, and overall survival (OS) were significantly better with inotuzumab ozogamicin versus SC in patients with CD22 positivity ≥90%. Fewer patients had CD22 positivity <90%; for whom, response rates were higher with inotuzumab ozogamicin versus SC, but DoR and OS appeared similar. Similar trends were evident in quartile analyses of CD22 MESF and CD22 positivity per local laboratory. Among inotuzumab ozogamicin–responding patients with subsequent relapse, decrease in CD22 positivity and receptor density was evident, but not the emergence of CD22 negativity. Rates of grade ≥3 hematologic adverse events (AEs) were similar and hepatobiliary AEs rate was higher for inotuzumab ozogamicin versus SC. No apparent relationship was observed between the rates of hematologic and hepatic AEs and CD22 expression. Conclusions: Inotuzumab ozogamicin demonstrated a favorable benefit–risk profile versus SC in patients with higher and lower CD22 expression. Patients with high CD22 expression and normal cytogenetics benefited the most from inotuzumab ozogamicin therapy.
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U2 - 10.1158/1078-0432.CCR-20-2399
DO - 10.1158/1078-0432.CCR-20-2399
M3 - Article
C2 - 33602684
AN - SCOPUS:85106211895
SN - 1078-0432
VL - 27
SP - 2742
EP - 2754
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 10
ER -