Loss of CD22 expression and expansion of a CD22dim subpopulation in adults with relapsed/refractory B-lymphoblastic leukaemia after treatment with Inotuzumab-Ozogamicin

Reinert, Jochim; Beitzen-Heineke, Antonia; Wethmar, Klaus; Stelljes, Matthias; Fiedler, Walter; Schwartz, Stefan

doi:10.1007/s00277-021-04601-0

Cited by 11 publications

(6 citation statements)

References 19 publications

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“…15 Furthermore, response in a CD22-negative patient was also described in a case report. 37 Thus, INO might be active in CD22-negative patients and/or those with very dim CD22 [40][41][42] In our cohort, VOD/SOS occurred in only three patients, including one after allogeneic HSCT, although up to four INO cycles were administered prior to transplantation. These data compare favorably to previously reported data.…”

Section: Discussionmentioning

confidence: 74%

Characteristics and outcome of patients with acute myeloid leukemia and trisomy 4

et al. 2022

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We retrospectively studied 125 patients with acute myeloid leukemia and trisomy 4 (median age at diagnosis, 58 years; range, 16-77 years) treated between 2000 and 2019 within a multicenter study. Trisomy 4 was the sole abnormality in 28 (22%) patients and additional abnormalities were present in 97 (78%) patients. Twenty-two (22%) and 15 (15%) of 101 tested patients harbored NPM1 and FLT3-ITD mutations. Two (3%) of 72 tested patients had double CEBPA mutations. Data on response to intensive anthracycline-based induction therapy were available for 119 patients. Complete remission was achieved in 67% (n=80) and the early death rate was 5% (n=6). Notably, patients with trisomy 4 as sole abnormality had a complete remission rate of 89%. Allogeneic hematopoietic cell transplantation was performed in 40 (34%) patients, of whom 19 were transplanted in first complete remission. The median follow-up of the intensively treated cohort was 5.76 years (95% confidence interval [95% CI]: 2.99-7.61 years). The 5-year overall survival and relapse-free survival rates were 30% (95% CI: 22-41%) and 27% (95% CI: 18-41%), respectively. An Andersen-Gill regression model on overall survival revealed that favorable-risk according to the European LeukemiaNet classification (hazard ratio [HR]=0.34; P=0.006) and trisomy 4 as sole abnormality (HR=0.41; P=0.01) were favorable factors, whereas age with a difference of 10 years (HR=1.15; P=0.11), female gender (HR=0.74; P=0.20) and allogeneic hematopoietic cell transplantation (HR=0.64; P=0.14) did not have an significant impact. In our cohort, patients with trisomy 4 as their sole abnormality had a high complete remission rate and favorable clinical outcome. Allogeneic hematopoietic cell transplantation did not seem to improve overall survival.

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Section: Discussionmentioning

confidence: 74%

Characteristics and outcome of patients with acute myeloid leukemia and trisomy 4

et al. 2022

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“… 15 Furthermore, response in a CD22-negative patient was also described in a case report. 37 Thus, INO might be active in CD22-negative patients and/or those with very dim CD22 expression, but this remains to be elucidated in larger studies. Recent data from the INO-VATE trial suggest that patients with high (≥90%) CD22 expression levels had a higher CR rate compared to those with <90% expression (42.1% [n=45/107] vs .…”

Section: Discussionmentioning

confidence: 98%

Outcome of relapsed or refractory acute B-lymphoblastic leukemia patients and <i>BCR-ABL</i>-positive blast cell crisis of B-lymphoid lineage with extramedullary disease receiving inotuzumab ozogamicin

et al. 2022

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Acute lymphoblastic leukemia (ALL) can relapse in the extramedullary compartment, with or without medullary involvement. Response to treatment may be unique. We evaluated response to inotuzumab ozogamicin (INO) in 31 relapsed/refractory (r/r) BALL patients with extramedullary disease (EMD). Median age was 31 (range, 19-81) years. All patients were heavily pretreated, including allogeneic hematopoietic stem cell transplantation (allo-HCT; n=18). Overall response rate after two INO cycles was 84% (complete remission (CR), 55%; partial remission (PR), 29%; resistant disease (PD), 13%; early death, 3%). Median follow-up was 29 months and median overall survival (OS) 12.8 months. One-year and 2-year OS rates were 53% (95%-CI, 37-76%) and 18% (95%-CI, 8-43%), respectively. Age had no impact on OS when assessed as a continuous variable or dichotomized at 60 years. Twelve patients proceeded to allo-HCT (CR, n=6; PR, n=3; PD, n=3). Prior to allo-HCT, eight patients received ≤2 and four patients 3-4 INO cycles. Sinusoidal obstruction syndrome was reported in three patients, including one after transplant. Allo-HCT evaluated as a time-dependent variable had no impact on OS. INO seems to be effective as debulking strategy in r/r-ALL with EMD. However, INO followed by allo-HCT seems not to be effective in maintaining long term disease control.

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“…Resistance to CD20-targeted therapies encompasses a spectrum of mechanisms, ranging from alterations in CD20 antigen levels to compromised immune system effector functions, and extending to diverse mechanisms of immune evasion (Figure 4). One of the main causes of resistance is the loss of the CD20 antigen on the surface of the target cell, which can be caused by changes in the expression of the MS4A1 gene, including silenced expression and alternative splicing Frontiers in Immunology frontiersin.org 10 (28,(155)(156)(157)(158). A recent study has shown that the gene encoding CD20 in both healthy and malignant B cells is alternatively spliced into four 5'-UTRs variants, of which especially variants V3 and V4 support robust translation.…”

Section: Resistance To Cd20directed Immunotherapiesmentioning

confidence: 99%

Anti-tumor Activity of Cytotoxic Immune Cells: Basic Research and Clinical Perspectives

2024

Frontiers Research Topics

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Frontiers is more than just an open access publisher of scholarly articles: it is a pioneering approach to the world of academia, radically improving the way scholarly research is managed. The grand vision of Frontiers is a world where all people have an equal opportunity to seek, share and generate knowledge. Frontiers provides immediate and permanent online open access to all its publications, but this alone is not enough to realize our grand goals. Frontiers journal seriesThe Frontiers journal series is a multi-tier and interdisciplinary set of openaccess, online journals, promising a paradigm shift from the current review, selection and dissemination processes in academic publishing. All Frontiers journals are driven by researchers for researchers; therefore, they constitute a service to the scholarly community. At the same time, the Frontiers journal series operates on a revolutionary invention, the tiered publishing system, initially addressing specific communities of scholars, and gradually climbing up to broader public understanding, thus serving the interests of the lay society, too. Dedication to qualityEach Frontiers article is a landmark of the highest quality, thanks to genuinely collaborative interactions between authors and review editors, who include some of the world's best academicians. Research must be certified by peers before entering a stream of knowledge that may eventually reach the public -and shape society; therefore, Frontiers only applies the most rigorous and unbiased reviews. Frontiers revolutionizes research publishing by freely delivering the most outstanding research, evaluated with no bias from both the academic and social point of view. By applying the most advanced information technologies, Frontiers is catapulting scholarly publishing into a new generation. What are Frontiers Research Topics?Frontiers Research Topics are very popular trademarks of the Frontiers journals series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area.

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Loss of CD22 expression and expansion of a CD22dim subpopulation in adults with relapsed/refractory B-lymphoblastic leukaemia after treatment with Inotuzumab-Ozogamicin

Cited by 11 publications

References 19 publications

Characteristics and outcome of patients with acute myeloid leukemia and trisomy 4

Characteristics and outcome of patients with acute myeloid leukemia and trisomy 4

Outcome of relapsed or refractory acute B-lymphoblastic leukemia patients and <i>BCR-ABL</i>-positive blast cell crisis of B-lymphoid lineage with extramedullary disease receiving inotuzumab ozogamicin

Anti-tumor Activity of Cytotoxic Immune Cells: Basic Research and Clinical Perspectives

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