Strålande nyhet för Epicept!

European Leukemia Net (ENL) är ett Europeiskt nätverk bestående av ledande hematologer. En av deras uppgifter är att skriva riktlinjer för behandling av aml - patienter. Dessa riktlinjer ÄR betydelsefulla på nationell nivå då många EU-länder följer dessa europeiska riktlinjer för behandling. Nyligen hade ENL ett medlemsmöte där behandling av AML-patienter i remission togs upp. Epicepts läkemedel Ceplene har tagits upp och beskrivningen är milt uttryckt glädjande.

Viktigaste är att behandling med Ceplene/Il2 nämns som ett möjligt paradigmskifte i behandling av patienter i remission. Frågan blir: Är det viktigt? Jag svarar: Har påven en lustig mössa?

Full text från mötet nedan

A novel approach of IL-2 directed treatment is based on the in vitro observation that histamine dihydrochloride (HDC, CepleneR) can reduce the inhibitory effects of myeloid-derived suppressor cells and thus protect T-cells and NK-cells and synergises with IL-2 to induce killing of leukemic cells. Feasibility studies in melanoma and AML have shown that cytotoxic lymphocytes are more efficiently activated by the combination of HDC/IL-2 than by IL-2 alone and also that the administration of HDC/IL-2 approved to be safe.

The results from a phase III randomised controlled trial in 320 patients with AML ranging from 18-84 years of which 39% were older than 60 y, 260 were in CR1 and 59 in subsequent CR were published by Mats B rune in B lood 2006. HDC/IL-2 (low dose!) was administered subcutaneously in repeated 3-week courses. In cycle 1-3 off-treatment periods were 3 weeks, in cycle 4-10 4 weeks. A total of 10 courses of HDC (CepleneR)/IL-2 were given during 18 months, thus coinciding with the period of highest relapse risk. Patients received HDC 0.5mg and IL-2 16.400 U /kg subcutaneously twice a day and treated safely themselves at home without supervision throughout the trial. The control arm received no treatment and was only observed.

The primary trial endpoint was improvement of leukemia-free survival (LFS), the trial met its primary endpoint and demonstratedthat the combination of HDC (CepleneR)/IL-2 improved the L FS by reducing the incidence of relapse at 3 years by approximately 50% (p=0.008, log rank test). For patients in CR1 3-year L FS estimates 40% (HDC/IL-2) compared with 26% (controlarm)

The prevention of relapse was particularly pronounced in patients < 60 years (p=0.005), but a strong treatment effect was observed also in patients < 70 years (p=0.0047). The trial was not powered for differences in survival however a trend towards improved overall survival (OS) was observed with a 64-week prolongation of median OS for patients receiving CepleneR/IL-2.

The side-effect profile for the HDC (CepleneR) /IL-2 combination was typically mild to moderate and there were no therapyrelated deaths. Severe IL-2 related toxicities were not observed because the dose of IL-2 was considerably lower than in other trials. The E ORTC QLC 30 analysis showed no significant impairment of global health status or quality of life in the CepleneR/IL-2 treated patients.

Conclusion
Maintenance therapy after induction and consolidation treatment is generally not recommended in AML. However immunotherapy can change the paradigm. The combination of HDC (CepleneR) /IL-2 is the first and only approved remission maintenance immunotherapy for AML and has the potential to significantly improve post-consolidation management of AML patients. As authorized by the EMEA, HDC (CepleneR) is administered in conjunction with low-dose IL-2 and is indicated as maintenance therapy for adult patients with AML in first remission.

Slutligen vill jag tacka Flex 2 på avanzas forum som har luskat fram denna nyhet.

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