VANDA regimen followed by blinatumomab leads to favourable outcome in patients with Philadelphia chromosome‐negative B‐precursor acute lymphoblastic leukaemia in first relapse

Abstract

Adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (R/R BCP-ALL) have a dismal prognosis. 1 Intensive chemotherapy (CT) leads to complete remission (CR) in fewer than 40% of patients and there is no standard schedule. 2 Long-term overall survival (OS) rates are under 20% at 5 years, but prolonged OS is possible for the small subset of patients achieving a CR and proceeding to allogeneic stem cell transplantation (HSCT). 2 Blinatumomab, a CD19/CD3 bispecific T cell engager, has shown its superiority over CT for R/R BCP-ALL and is a valuable option as a bridge to transplantation. 3 Sequential addition of blinatumomab improves outcome for patients in CR with positive measurable residual disease (MRD) after CT, in first line as well as in R/R settings. 4,5 However, concomitant administration of CT and blinatumomab in R/R BCP-ALL to increase the complete response rate has not been explored. The VANDA regimen (etoposide, high-dose cytarabine, mitoxantrone, dexamethasone, asparaginase), an intensive paediatric CT, is used for patients with R/R BCP-ALL before HSCT. Here, we report the outcome of 17 Philadelphia chromosome-negative (Ph−) patients in first relapse BCP-ALL consecutively treated with combination of VANDA and blinatumomab (VANDA-BLI regimen). PATIE N TS A N D ST U DY PROTOCOLThis analysis was conducted at the Bordeaux University Hospital (France). All adult patients (>18 years) with Ph− R/R BCP-ALL diagnosed between January 2016 and June 2021 and considered eligible for intensive CT by clinicians (regarding age and comorbidities) were consecutively treated with VANDA-BLI, and included in this report. All patients received an anthracycline-containing regimen at first line, including a paediatric or paediatric-inspired protocols in 15 patients. According to French law on ethics, patients were

Blinatumomab consolidation for adult B-cell acute lymphoblastic leukemia in first and second complete remission

“… 5 , 6 Moreover, the use of blinatumomab after an attempt to reduce the leukemic burden rather than in overt relapse is now supported by many real-world studies or retrospective analyses of prospective trials showing the prognostic impact of bone marrow tumor infiltration before blinatumomab administration. 7 , 8 , 9 , 10 In the present real-world study, we aim at describing the outcome of adult patients who received blinatumomab in first or second complete remission (CR). As an internal comparator, we also reported on patients from the same institutions who received blinatumomab in overt relapse.…”

Enhancing Leukemia Treatment: The Role of Combined Therapies Based on Amino Acid Starvation

“…For instance, blinatumomab, a bi-specific T cell engager to recognize the CD19 antigen on the B cell surface, has shown activity in refractory/relapsed (R/R) BCP-ALL. When used in combination with VANDA (etoposide, cytarabine, mitoxantrone, dexamethasone, and asparaginase), it achieved complete remission in a significant proportion of patients [ 64 ]. While in a case report, combining inotuzumab ozogamicin (anti-CD22) with high-dose methotrexate and pegaspargase in a patient with extramedullary B-ALL resulted in toxic liver damage [ 65 ].…”

Trending Drugs Combination to Target Leukemia associated Proteins/Genes: using Graph Neural Networks under the RAIN Protocol

“…For further details and characteristics, please refer to Table 3 [171]- [205]. Additionally, the structures of the drugs used in the studies are displayed in Figure 4, while Table 4 provides an overview of the drug properties [171]- [205].…”