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27 november 2018: Bron: Dovepress: Published online 2018 Oct 2

Blinatumomab, een vorm van immuuntherapie, heeft bewezen effectief te zijn in zowel minimale ziekte als bij een recidief van Acute Lymfatische Leukemie - All.

In R / R B-cel ALL werd blinatumomab geassocieerd met een verbeterde mediane totale overleving van 7,7 maanden versus 4,0 maanden met traditionele chemotherapie (HR voor overlijden, 0,71, 95% betrouwbaarheidsinterval, 0,55-0,93, P = 0,01).

De fase III TOWER studie liet nog veel indrukwekkender resultaten zien voor blinatumomab met gemiddeld genomen een verdubbeling van de overall overleving in vergelijking met standaard chemotherapie:

Een groep van 405 patiënten werd op basis van 2:1 verhoudiing gerandomiseerd ingedeeld of voor blinatumomab (n=267) of chemotherapie (n=134). Mediane overall overleving (OS) was 7.7 maanden in de blinatumomab groep(n=267) en 4.0 maanden in de chemotherapiegroep (HR for death, 0.71; P=0.01).
Ziektevrije tijd op 6-maanden meting bleek 31% voor blinatumomab vs 12% voor chemo,
P<0.001) en complete remissies  (CR) verdubbelden van 33.6% voor blinatumomab versus 15.7% voor chemo, P<0.001).

Deze resultaten tonen niet alleen aan dat blinatumomab is een effecteive behandeling voor een recidief van ALL, maar blijkt ook kosten efectiever te zijn dan de standaard chemotherapie.

En bedenk daarbij dat alle patienten zwaar waren voorbehandeld en in principe in laatste fase van hun leven en ongeneeslijk.

Hier het werkingsmechanisme van blinatumomab:

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Mechanism of blinatumomab.

Notes: Immunomodulatory therapy of cancer with T-cell-engaging BiTE antibody blinatumomab. Reprinted from Experimental Cell Research. 317(9). Nagorsen D and Baeuerle PA. Immunomodulatory therapy of cancer with T-cell-engaging BiTE antibody blinatumomab. 1255–126, 2011, with permission from Elsevier.

Blinatumomab heeft wel specifieke bijwerkingen in vergelijking met chemotherapie, met name het cytokine-afgifte-syndroom en neurologische toxiciteiten. In vergelijking met standaard chemotherapie, hebben patiënten een betere kwaliteit van leven en minder financiële lasten (In amerika moet vaak nog worden betaald voor medische behandelingen) . Gebruikmakend van de Europese organisatie voor onderzoek en behandeling van de kwaliteit van leven van kanker, deden met blinatumomab behandelde patiënten het beter en hadden een langere tijd tot ziekteprogressie of overlijden (global health status/quality of life subscale: HR 0.66; 95% CI 0.48–0.92; P=0.009) in vergelijking met traditionele chemotherapie. Hier een reviewstudie van de effecten van blinatumomab bij zowel volwassenen als kinderen met ALL - Acute Lymfatische Leukemie. 

Studies met blinatumomab uit deze reviewstudie:

Table 1

Clinical trials of blinatumomab and outcomes

Clinical trialPhase of trialPopulationDosingPrimary end pointsSecondary end pointsNumber of patients
Topp et al, 201114 Phase II Median age: 47 years; relapsed or refractory MRD B-cell ALL 15 µg/m2/24 hours over 4 weeks with 2 weeks off of treatment for a total of 6-week cycle MRD response rates after one cycle of blinatumomab None 20
Topp et al, 20149 Phase II Median age: 32 years; relapsed or refractory B-cell ALL Cohort 1: 15 µg/m2/24 hours; cohort 2: initial dose of the first week of 5 µg/m2/24 hours for the first week and if able increased to 15 µg/m2/24 hours; cohort 3: initiated at 5 µg/m2/24 hours then 15 µg/m2/24 hours, and then to 30 µg/m2/24 hours CR or CRh 69% MRD RR 88%; RFS 7.6 months; median OS 9.8 months 36
Von Stackelberg et al, 201620 Phase I/II Median age: 8 years; relapsed or refractory B-cell ALL Phase I: maximum tolerated dose of blinatumomab was 15 µg/m2/24 hours, initiated at 5 µg/m2/24 hours for the first week and increased to 15 µg/m2/24 hours Phase I: MTD; Phase II: CR rate within the first two cycles 32% Phase II: proportion of patients HSCT post-Tx among responders 48%; RFS among responders 4.4 months; OS all patients (70) 7.5 months Phase I: 49; Phase II: 44
Kantarjian et al, 201711 Phase III Blinatumomab: median age 40.8 years; chemotherapy median age 41.1 years; relapsed or refractory B-cell ALL 9 µg/24 hours for the first week, and 28 µg/24 hours for the remainder of the 4 weeks, and 2 weeks off Blinatumomab vs chemotherapy: OS: 7.7 months vs 4.0 months (95% CI, 5.6–9.6) Blinatumomab vs chemotherapy: CR with CRh within 12 weeks: 24% vs 16%; P<0.001; CR, CRh, or CRi within 12 weeks, 44% vs 25%; P<0.001 Blinatumomab: 271; chemotherapy 134
Martinelli et al, 201713 Phase II Median age: 55 years; Ph-positive B-cell ALL relapsed and refractory 9 µg/24 hours for the first week, and 28 µg/24 hours for the remainder of the 4 weeks, and 2 weeks off CR or CRh during first two cycles: 36% MRD RR during the first two cycles: 88%; RFS: 6.7 months; OS: 7.1 months; HSCT after remission:44% 45
Gökbuget et al, 201819 Phase II Median age 45.0 years; refractory MRD B-cell ALL 15 µg/m2/24 hours over 4 weeks with 2 weeks off of treatment for a total of 6-week cycle MRD response rates after one cycle of blinatumomab RR: 78% RFS at 18 months: 54% 113

Abbreviations: MRD, minimal residual disease; ALL, acute lymphoblastic leukemia; RR, response rate; CR, complete remission; CRh, complete remission with partial hematological recovery; RFS, relapse-free survival; OS, overall survival; MTD, maximum tolerated dose; HSCT, hematopoietic stem cell transplantation; Cri, complete remission with incomplete blood count recovery; Ph, Philadelphia chromosome; Tx, treatment.

Conclusie van de auteurs van deze reviewstudie:

Blinatumomab is door de FDA goedgekeurd voor zowel MRD als voor R / R B-cell ALL. Zoals opgemerkt in deze review, is het een effectieve behandeling in vergelijking met chemotherapie en wordt het meestal goed verdragen, maar heeft het bijwerkingen zoals CRS en neurologische toxiciteiten die moeten worden gemonitord. Blinatumomab wordt geassocieerd met betere kwaliteit van leven en economisch voordeel in vergelijking met traditionele chemotherapie.

Blinatumomab heeft de neiging het meest effectief te zijn bij patiënten met een lage B-cel ALL- of MRD-positiviteit bij lage tumorbelasting. Het wordt ook gebruikt als een brug naar HSCT. Van blinatumomab is aangetoond dat het succesvol is als monotherapie, maar toekomstige studies zullen nodig zijn om te bepalen of een combinatietherapie een grotere respons zal hebben en dus te vertalen in verdere verbeteringen in OS en kwaliteit van leven voor patiënten met MRD of R / R B-cel ALL.

Het volledige studierapport: Impact of blinatumomab on patient outcomes in relapsed/refractory acute lymphoblastic leukemia: evidence to date is gratis in te zien.

Heir het abstract van de studie met referentielijst:

Blinatumomab is FDA-approved for both MRD and for R/R B-cell ALL. Blinatumomab is an effective treatment when compared to chemotherapy and it is usually well-tolerated, but has side effects such as CRS and neurological toxicities that need to be monitored. Blinatumomab is associated with better quality of life scores as well as economic benefit when compared to traditional chemotherapy

. 2018; 9: 329–337.
Published online 2018 Oct 2. doi:  [10.2147/PROM.S149420]
PMCID: PMC6173178
PMID: 30323696

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

Abstract

Relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) is associated with a poor prognosis in both children and adults. Traditionally, there were limited options for salvage therapy, which consisted mostly of conventional chemotherapy. However, in the past 5 years, novel agents have changed our treatment strategies in this population. Blinatumomab, a bispecific CD19 directed CD3 T-cell engager, has shown to be effective in both minimal residual disease and R/R B-cell ALL. In R/R B-cell ALL, blinatumomab was associated with an improved median overall survival of 7.7 months vs 4.0 months with traditional chemotherapy (HR for death, 0.71; 95% CI, 0.55–0.93; P=0.01). It has distinctive side effects as compared to chemotherapy, specifically cytokine release syndrome and neurological toxicities. When compared to standard of care chemotherapy, patients have higher quality of life scores and less financial burden. Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, blinatumomab-treated patients fared better and had a longer time to deterioration or death (global health status/quality of life subscale: HR 0.66; 95% CI 0.48–0.92; P=0.009) compared to conventional chemotherapy. Using an incremental cost effective ratio threshold of US$150,000 per quality adjusted life year, blinatumomab was determined to be more cost effective compared to chemotherapy with a probability of 73.7%. This review summarizes the current and future data with blinatumomab in R/R B-cell ALL in the adult and pediatric population.

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Articles from Patient Related Outcome Measures are provided here courtesy of Dove Press

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