Mini-hyper-CVD plus inotuzumab ozogamicin, with or without blinatumomab, in the subgroup of older patients with newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukaemia: long-term results of an open-label phase 2 trial.

BACKGROUND

The outcome of older patients with B-cell acute lymphocytic leukaemia is inferior to that in younger patients due to the adverse disease biology and their inability to tolerate intensive therapy. We aimed to study the long-term outcomes of inotuzumab ozogamicin with or without blinatumomab in combination with low-intensity chemotherapy in these patients.

METHODS

For this open-label phase 2 trial, patients aged 60 years or older with newly diagnosed, Philadelphia-chromosome negative, B-cell acute lymphocytic leukaemia, and an ECOG performance status of 3 or lower were eligible. This study was conducted at the University of Texas MD Anderson Cancer Center. The induction chemotherapy consisted of mini-hyper-CVD and has been published before; inotuzumab ozogamicin was administered intravenously on day 3 of the first four cycles at a dose of 1·3-1·8 mg/m

RESULTS

Between Nov 11, 2011, and March 31, 2022, 80 patients were enrolled and treated (32 female and 48 male patients; median age 68 years [IQR 63-72]), 31 of whom were treated after the protocol amendment. With a median follow-up of 92·8 months (IQR 8·8-67·4), the 2-year progression-free survival was 58·2% (95% CI 46·7-68·2) and 5-year progression-free survival was 44·0% (31·2-54·3). At a median follow-up of 104·4 months (IQR 6·6-89·2) for the patients treated before the protocol amendment and 29·7 months (8·8-41·0) for those treated after the protocol amendment, median progression-free survival did not differ significantly between the two groups (34·7 months [95% CI 15·0-68·3] vs 56·4 months [11·3-69·7]; p=0·77). The most common grade 3-4 events were thrombocytopenia in 62 (78%) patients and febrile neutropenia in 26 (32%) patients. Six (8%) patients developed hepatic sinusoidal obstruction syndrome. There were eight (10%) deaths due to infectious complications, nine (11%) from complications related to secondary myeloid malignancy, and four (5%) from sinusoidal obstruction syndrome.

INTERPRETATION

Inotuzumab ozogamicin with or without blinatumomab added to low-intensity chemotherapy showed promising activity in terms of progression-free survival in older patients with B-cell acute lymphocytic leukaemia. Further attenuation of the chemotherapy regimen might improve tolerability while maintaining efficacy in older patients.

FUNDING

Pfizer and Amgen.

Informations de copyright

Copyright © 2023 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests EJ reports research grants from AbbVie, Adaptive Biotechnologies, Amgen, Pfizer, and Takeda; and consultancy fees from AbbVie, Adaptive Biotechnologies, Amgen, Bristol Myers Squibb, Genentech, Incyte, Novartis, Pfizer, and Takeda. NJS reports research grants from Takeda Oncology, Astellas Pharma, Xencor, and Stemline Therapeutics; consultancy fees from Pfizer and Jazz Pharmaceuticals; and honoraria from Novartis, Amgen, Sanofi, and BeiGene. ND reports research funding from Daiichi-Sankyo, Bristol Myers Squibb, Pfizer, Gilead, Servier, Genentech, Astellas, Daiichi-Sankyo, Abbvie, Hanmi, Trovagene, FATE therapeutics, Amgen, Novimmune, Glycomimetics, Trillium, and ImmunoGen; and served in a consulting or advisory role for Daiichi-Sankyo, Bristol Myers Squibb, Arog, Pfizer, Novartis, Jazz, Celgene, AbbVie, Astellas, Genentech, Immunogen, Servier, Syndax, Trillium, Gilead, Amgen, Shattuck labs, and Agios. HK reports research grants from AbbVie, Amgen, Ascentage, Bristol Myers Squibb, Daiichi-Sankyo, Immunogen, Jazz, Novartis, and Pfizer; and honoraria from AbbVie, Amgen, Aptitude Health, Ascentage, Astellas Health, Astra Zeneca, Ipsen, Pharmaceuticals, KAHR Medical, NOVA Research, Novartis, Pfizer, Precision Biosciences, and Taiho Pharmaceutical Canada. All other authors declare no competing interests.