Inlichtingingen over onderstaande studie kunnen worden ingewonnen bij Zwi N. Berneman, Division of Hematology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Antwerp, Belgium; e-mail: eb.azu@namenreb.iwz.
22 maart 2021: Bron: Blood. 2017 Oct 12; 130(15): 1713–1721.
Een recidief krijgen is een groot probleem bij acute myeloïde leukemie (AML) en heeft invloed op de mediane overall overleving. Als patiënten met AML in remissie komen door chemotherapie en aansluitend dendritische celtherapie krijgen versterkt met een Wilms Tumor 1 mRNA vaccin dan blijft een remissie veel langer weg of helemaal weg dan zonder deze extra dendritische celtherapie. In een fase 2 studie onderzochten onderzoekers deze aanpak bij 30 patiënten met AML, die weliswaar in een complete remissie waren van hun AML, maar waarvan zij wisten dat die een heel hoog risico op een recidief liepen.
Er was een aantoonbare antileukemische respons bij 13 patiënten. Negen patiënten bereikten een moleculaire remissie, zoals aangetoond door normalisatie van WT1-transcriptniveaus, waarvan er 5 duurzaam bleken na een mediane follow-up van 109,4 maanden. Stabiele ziekte werd bereikt bij 4 andere patiënten. De totale mediane overall overleving (OS) na vijf jaar was hoger bij de patiënten die goed reageerden op de dendritische celtherapie dan bij de patiënten die niet of nauwelijks reageerden. Een verdubbeling van de overall overleving op 5 jaar dus. (53,8% versus 25,0%; P = 0,01).
Bij patiënten die de dendritische cellen kregen na de 1e complete remissie, werd er bij 25 procent een recidief gezien. De recidief vrije tijd op 5-jaars meting was stukken hoger bij responders dan bij non-responders (50% versus 7,7%; P <. 0001).
Bij patiënten van ≤ 65 jaar en > 65 jaar die DC kregen na 1e remissie, was de 5-jaars overall overleving respectievelijk 69,2% en 30,8%, vergeleken met 51,7% en 18% zoals geregistreerd in de Zweedse Acute Leukemia Registry.
Kaplan-Meier curves of the OS data. The values on the curves are 5-year relative survival from the start of WT1/DC vaccination; the values underneath in gray (A-C) are 5-year relative survival data from SEER (observed survival of newly diagnosed patients with AML included in SEER*Stat database,50 whereby the following case selection criteria were applied: age [minimum age, 30 years; maximum age, 79 years], race , and year of diagnosis [2005-2012]; the patient with an undefinable response was not included in panel D). For median OS (mOS), values in brackets represent median follow-up. n.r., not reached.
Het volledige studieverslag met grafieken en meer details is gratis in te zien.
Hier het abstract:
Blood. 2017 Oct 12; 130(15): 1713–1721.
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Key Points
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WT1 mRNA-electroporated DCs can prevent or delay relapse in 43% of patients with AML in remission after chemotherapy.
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OS compares favorably with the new survival data from the Swedish Acute Leukemia Registry and correlates with molecular and WT1-specific CD8+ T-cell responses.
Abstract
Relapse is a major problem in acute myeloid leukemia (AML) and adversely affects survival. In this phase 2 study, we investigated the effect of vaccination with dendritic cells (DCs) electroporated with Wilms’ tumor 1 (WT1) messenger RNA (mRNA) as postremission treatment in 30 patients with AML at very high risk of relapse. There was a demonstrable antileukemic response in 13 patients. Nine patients achieved molecular remission as demonstrated by normalization of WT1 transcript levels, 5 of which were sustained after a median follow-up of 109.4 months. Disease stabilization was achieved in 4 other patients. Five-year overall survival (OS) was higher in responders than in nonresponders (53.8% vs 25.0%; P = .01). In patients receiving DCs in first complete remission (CR1), there was a vaccine-induced relapse reduction rate of 25%, and 5-year relapse-free survival was higher in responders than in nonresponders (50% vs 7.7%; P < .0001). In patients age ≤65 and >65 years who received DCs in CR1, 5-year OS was 69.2% and 30.8% respectively, as compared with 51.7% and 18% in the Swedish Acute Leukemia Registry. Long-term clinical response was correlated with increased circulating frequencies of polyepitope WT1-specific CD8+ T cells. Long-term OS was correlated with interferon-γ+ and tumor necrosis factor-α+ WT1-specific responses in delayed-type hypersensitivity-infiltrating CD8+ T lymphocytes. In conclusion, vaccination of patients with AML with WT1 mRNA-electroporated DCs can be an effective strategy to prevent or delay relapse after standard chemotherapy, translating into improved OS rates, which are correlated with the induction of WT1-specific CD8+ T-cell response. This trial was registered at www.clinicaltrials.gov as #NCT00965224
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Articles from Blood are provided here courtesy of The American Society of Hematology
AML, Acute Myeloide Leukemie, WT1 mRNA gemoduleerde dendritische cellen, recidief
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