Association of leukemic molecular profile with efficacy of inotuzumab ozogamicin in adults with relapsed/refractory ALL.
Yaqi ZhaoA Douglas LairdKathryn G RobertsRolla L YafawiHagop M KantarjianDaniel J DeAngeloMatthias StelljesMichaela LiedtkeWendy StockNicola GökbugetSusan M O'BrienElias J JabbourRyan D CassadayMelanie R LoydScott R OlsenGeoffrey A NealeXueli LiuErik VandendriesAnjali S AdvaniCharles G MullighanPublished in: Blood advances (2024)
The phase 3 INO-VATE trial demonstrated higher rates of remission, measurable residual disease negativity, and improved overall survival for patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) who received inotuzumab ozogamicin (InO) vs standard of care chemotherapy (SC). Here we examined associations between genomic alterations and the efficacy of InO. Of 326 randomized patients, 91 (InO, n=43; SC, n=48) had samples evaluable for genomic analysis. The spectrum of gene fusions and other genomic alterations observed was comparable with prior studies of adult ALL. Responses to InO were observed in all leukemic subtypes, genomic alterations, and risk groups. Significantly higher rates of complete remission (CR)/CR with incomplete count recovery rates were observed with InO vs SC in patients with BCR::ABL1-like ALL (85.7% [6/7] vs 0% [0/5] P=0.0076), with TP53 alterations (100% [5/5] vs 12.5% [1/8], P=0.0047), and in the high-risk BCR::ABL1- (BCR::ABL1-like, low hypodiploid, KMT2A-rearranged) group (83.3% [10/12] vs 10.5% [2/19]; P<0.0001). This retrospective, exploratory analysis of the INO-VATE trial demonstrated potential for benefit with InO for patients with R/R ALL across leukemic subtypes, including BCR::ABL1-like ALL, and for those bearing diverse genomic alterations. Further confirmation of the efficacy of InO in patients with R/R ALL exhibiting the BCR::ABL1-like subtype or harboring TP53 alterations is warranted. This trial was registered at www.clinicaltrials.gov as no. NCT01564784.
Keyphrases
- acute lymphoblastic leukemia
- chronic myeloid leukemia
- tyrosine kinase
- allogeneic hematopoietic stem cell transplantation
- phase iii
- copy number
- acute myeloid leukemia
- phase ii
- study protocol
- clinical trial
- healthcare
- end stage renal disease
- open label
- randomized controlled trial
- squamous cell carcinoma
- newly diagnosed
- disease activity
- peripheral blood
- genome wide
- chronic kidney disease
- gene expression
- double blind
- hodgkin lymphoma
- chronic pain
- single molecule
- diffuse large b cell lymphoma