Impact of blinatumomab on patient outcomes in relapsed/refractory acute lymphoblastic leukemia: evidence to date

Hathaway, Lindsey J.; Sen, Jeremy; Keng, Michael

doi:10.2147/prom.s149420

Cited by 19 publications

(13 citation statements)

References 23 publications

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“…Our findings demonstrate an acceptable safety profile and high response rate with blinatumomab in pediatric patients with r/r BCP-ALL. Blinatumomab is generally better tolerated compared with chemotherapy 5,8,9 ; however, it is associated with distinct AEs, including neurologic toxicities and CRS. In this study, such events at ≥grade 3 were infrequent.…”

Section: Dear Editormentioning

confidence: 99%

Blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia: results of the RIALTO trial, an expanded access study

et al. 2020

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Section: Dear Editormentioning

confidence: 99%

Blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia: results of the RIALTO trial, an expanded access study

et al. 2020

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“…Despite the excellent survival rates achieved in pediatric acute lymphoblastic leukemia [9,10], relapsed and refractory ALL represents a distinct entity with dismal prognosis and outcome [1][2][3][4][5][6][7][8][9].…”

Section: Discussionmentioning

confidence: 99%

“…Key words: blinatumomab; refractory or relapsed acute lymphoblastic leukemia (ALL); HSCT; immunotherapy Relapsed or refractory B-cell precursor (Bcp) acute lymphoblastic leukemia (ALL) is associated with dismal outcome and resistance to intensive chemotherapy regimens poses unique therapeutic challenges. [1][2][3][4][5][6][7][8][9] In the pediatric setting, novel immunotherapy approaches offer potential cure opportunities, inducing remission, mediating a successful bridge to allergenic hematopoietic stem cell transplantation (allo-HSCT) [1][2][3][4][5][6][7][8].…”

mentioning

confidence: 99%

Insights from the Greek experience of the use of Blinatumomab in pediatric relapsed and refractory acute lymphoblastic leukemia patients

Ampatzidou¹,

Kattamis²,

Baka³

et al. 2021

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Pediatric refractory or relapsed acute lymphoblastic leukemia (ALL) poses unique therapeutic challenges, with novel immunotherapy approaches offering potential cure opportunities. In this frame, the use of Blinatumomab may induce durable remissions, serving as a successful bridge to allergenic hematopoietic stem cell transplantation (allo-HSCT). Herein, we retrospectively summarize the Greek experience on pediatric relapsed/refractory B-cell precursor ALL patients that were treated with Blinatumomab in a compassionate, off-label setting as an effort to achieve disease clearance and proceed to allo-HSCT. In our cohort of 9 patients, 6/9 (66.7%) responded to Blinatumomab, achieving complete morphological remission (CR) after the 1st cycle, while minimal/measurable residual disease (MRD)-negativity (< 10-4) after the 1st cycle was achieved in 2/2 patients (100.0%) with prior CR. A successful bridge to HSCT was feasible in 5/9 patients (55.6%). Median relapse-free survival (RFS) was 3.0 months (range 0.5-21.4 months) and median overall survival (OS) was 8.7 months (range 1.4-47.1 months) for the whole pediatric cohort. There was a trend of prolonged survival among patients who achieved MRD response after the 1st Blinatumomab administration. MRD response (defined as the >=2-log reduction of MRD value before and after Blinatumomab administration), was associated with a median RFS/OS of 7.4/7.6 months, while lack of MRD response was associated with a median RFS/OS of 0.5/3.0 months, respectively. Novel therapeutic maneuvers, in order to overcome disease resistance, i.e. increased usage of Blinatumomab dose bination with donor lymphocyte infusions (DLIs), use of other immunotherapy salvage approaches (inotuzumabozogamicin), are herein discussed. Additionally, the optimal number of Blinatumomab cycles, the CD19-negative relapses and lineage switch, are also addressed. Our data although referred to a limited however refractory or relapsed and heavily pretreated number of patients, strongly suggest that Blinatumomab may well induce sustained remissions and serve as an effective bridge to HSCT. Whether immunotherapy combined with chemotherapy can outweigh the need for subsequent allo-HSCT, if incorporated into

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“…Blinatumomab is highly effective in both MRD+ and R/R B cell ALL. 117,118 Based on these favorable data, the role of blinatumomab was investigated as post-allo-HCT maintenance. 119 High-risk patients with ALL received blinatumomab 28 mcg daily for 4 weeks during 4 cycles at 3, 6, 9, and 12 months post-HCT.…”

Section: Immunotherapymentioning

confidence: 99%

Maintenance Strategies After Hematopoietic Cell Transplantation

2020

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Hematopoietic cell transplantation (HCT) is an essential component of potentially curative therapy for patients with hematologic malignancies. High‐dose chemotherapy with autologous (auto) stem cell rescue is used to overcome chemoresistance in multiple myeloma, non‐Hodgkin lymphoma, and Hodgkin lymphoma. Alternatively, poor‐risk acute leukemias rely on the graft versus leukemia effect of allogeneic (allo) products. Long‐term remissions are feasible with both auto‐ and allo‐HCT; however, disease relapse is the leading cause of death after HCT for many patients. In recognition of this, novel therapies are being investigated in the upfront, relapsed/refractory, and post‐HCT maintenance settings to deepen response and maintain disease control. To date, the most robust data to support this approach are in multiple myeloma, where post‐transplant maintenance therapy has improved clinical outcomes. In Hodgkin lymphoma, patients with high‐risk features may benefit from post–auto‐HCT vedotin (BV) regardless of pre‐HCT BV exposure. Apart from mantle cell lymphoma, where rituximab maintenance is generally accepted, post–auto‐HCT maintenance in other forms of NHL is less established. In patients who undergo allo‐HCT, the utilization of maintenance therapy is an important component of improving post‐HCT outcomes, however, an individualized approach that considers patient factors such as residual toxicity from HCT, an immature graft with poor graft function, infection, and graft‐versus‐host disease create a complex environment for aggressive interventions. Initiation of directed agents in patients with identified mutations prior to allo‐HCT, including FLT3 in acute myeloid leukemia and Philadelphia chromosome in acute lymphoid leukemia have generally improved post‐HCT outcomes. Ongoing studies are exploring the safety and efficacy of additional maintenance strategies post–allo‐HCT in an effort to further improve post‐HCT outcomes.

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Impact of blinatumomab on patient outcomes in relapsed/refractory acute lymphoblastic leukemia: evidence to date

Cited by 19 publications

References 23 publications

Blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia: results of the RIALTO trial, an expanded access study

Blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia: results of the RIALTO trial, an expanded access study

Insights from the Greek experience of the use of Blinatumomab in pediatric relapsed and refractory acute lymphoblastic leukemia patients

Maintenance Strategies After Hematopoietic Cell Transplantation

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