ALL-026: Evaluating Efficacy and Safety of Tisagenlecleucel Reinfusion Following Loss of B-Cell Aplasia in Pediatric and Young Adult Patients with Acute Lymphoblastic Leukemia: HESTER Phase II Study

2021 ◽  
Vol 21 ◽  
pp. S262-S263
Author(s):  
Michael W. Boyer ◽  
Sonali Chaudhury ◽  
Kara L. Davis ◽  
Timothy Alan Driscoll ◽  
Stephan A. Grupp ◽  
...  
2017 ◽  
Vol 52 (3) ◽  
pp. 268-276 ◽  
Author(s):  
Troy Z. Horvat ◽  
Amanda N. Seddon ◽  
Adebayo Ogunniyi ◽  
Amber C. King ◽  
Larry W. Buie ◽  
...  

Objective: To review the pharmacology, efficacy, and safety of Food and Drug Administration approved and promising immunotherapy agents used in the treatment of acute lymphoblastic leukemia (ALL). Data Sources: A literature search was performed of PubMed and MEDLINE databases (1950 to July 2017) and of abstracts from the American Society of Hematology and the American Society of Clinical Oncology. Searches were performed utilizing the following key terms: rituximab, blinatumomab, inotuzumab, ofatumumab, obinutuzumab, Blincyto, Rituxan, Gazyva, Arzerra, CAR T-cell, and chimeric antigen receptor (CAR). Study Selection/Data Extraction: Studies of pharmacology, clinical efficacy, and safety of rituximab, ofatumumab, obinutuzumab, inotuzumab, blinatumomab, and CAR T-cells in the treatment of adult patients with ALL were identified. Data Synthesis: Conventional chemotherapy has been the mainstay in the treatment of ALL, producing cure rates of approximately 90% in pediatrics, but it remains suboptimal in adult patients. As such, more effective consolidative modalities and novel therapies for relapsed/refractory disease are needed for adult patients with ALL. In recent years, anti-CD20 antibodies, blinatumomab, inotuzumab, and CD19-targeted CAR T-cells have drastically changed the treatment landscape of B-cell ALL. Conclusion: Outcomes of patients with relapsed disease are improving thanks to new therapies such as blinatumomab, inotuzumab, and CAR T-cells. Although the efficacy of these therapies is impressive, they are not without toxicity, both physical and financial. The optimal sequencing of these therapies still remains a question.


2009 ◽  
Vol 83 (6) ◽  
pp. 512-518 ◽  
Author(s):  
Christine Dudler ◽  
Mario Bargetzi ◽  
Andr�� Tichelli ◽  
Alois Gratwohl ◽  
Jakob R. Passweg ◽  
...  

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5016-5016 ◽  
Author(s):  
Leping Zhang ◽  
Xin Du ◽  
Yan Li ◽  
Zhen Cai ◽  
Kang Yu ◽  
...  

Abstract Background Clofarabine is a second generation purine nucleoside which inhibits DNA polymerase alpha and ribonucleotide reductase, leading to the depletion of intracellular deoxynucleotide triphosphate pools, disruption of mitochondrial function and apoptosis. A phase II study was conducted to evaluate the safety and efficacy of clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia (ALL) in China. Method Patients aged 1-21 years with histologically confirmed, relapsed and/or refractory ALL were eligible. Clofarabine was administered intravenously for 5 days at 52 mg/m2/d during induction and consolidation. The primary end point was overall remission rate (ORR; complete remission [CR] plus CR with incomplete counts [CRi]). Blood samples were obtained from patients who agreed to blood drawing for pharmacokinetic determinations. Results A total of 44 patients were treated in this study, in which 43 were evaluable for response. The median age was 13 years (range: 5 to 22 years), and the majority were B cell-ALL (75%, 33/44). The overall remission rate was 44.2% (19/43), including two complete remissions (CR), and 17 CRis. 39 patients had progressive disease at cut-off time, the overall median remission duration was 2.9 months, and the median remission duration was 3.4 months for patients achieved CR or CRi. Seven CR/CRi patients had chance to got HSCT after clofarabine treatment. Subgroup analysis showed that patients younger than 14 years and with B cell-ALL had a higher ORR than patients older than 14 years and with T cell-ALL, and the difference were statistically significant (age < 14 years vs. age ≥14 years: 60.9% vs. 25%, p =0.0308; B cell-ALL vs. T cell-ALL: 57.6% vs. 0, p=0.002). The most common (≥10%) adverse reactions (ADR) were hematological toxicity, gastrointestinal reaction, and abnormal liver function, and the most common grade 3/4 non-hematologic ADRs was ALT elevation (13.6%). PK analysis demonstrated that after multiple administrations the mean elimination half-life of clofarabine was 6.43 h, and the Tmax was around 2 h. The mean Cmax and exposure to clofarabine over the dosing period (AUC 0-24) achieved 581 ug/L and 2602.56 ug/L, respectively. It seems that there is no significant difference of PK profiles between Chinese and Caucasian patients. Conclusion Single clofarabine treatment is effective in Chinese pediatric patients with multiple relapsed or refractory ALL with acceptable safety profiles. Disclosures: No relevant conflicts of interest to declare.


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