A phase I/II feasibility vaccine study by autologous leukemic apoptotic corpse-pulsed dendritic cells for elderly AML patients

Skin Biopsy

Skin biopsy

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Summary

In this study, autologous leukemic apoptotic corpse-pulsed dendritic cells (DC) are used to investigate the feasibility of a vaccination in patients with acute myeloid leukemia (AML). There were no significant adverse events reported as a result of the study. In order to pinpoint the involvement of DC-vaccines with leukemic apoptotic bodies in older and younger AML populations, larger Phase 2 investigations are now necessary.

Patients characteristics

21 elderly patients with AML (male n = 14; median age: 74 years-old [range: 65–84], secondary AML n = 8) were pre-enrolled at diagnosis (n = 14 including 3 primary refractory) or at first relapse (n = 7, including 3 refractory after salvage regimen). With an ECOG ≤2, at least 50% of leukemic blasts in the bone marrow (BM) or peripheral blood at diagnosis and no contraindication to apheresis.

Methodology

Vaccine production
Patients were pre-included at diagnosis or first relapse. Leukemic cells (≥2.4×108 required) were collected over 1 or 2 days prior to chemotherapy. Blast apoptosis was induced by thermal shock (1 h at 42°C) followed 3 hours later by UVB irradiation (100 kJ/m2) and at least 20 hours of culture. Apoptotic blasts (>99% ToPro-3 fluorescent cells) were frozen at −196°C without DMSO.
Peripheral monocytes were collected by apheresis and cultured for 6 days. Immature DC (iDC) were then generated by addition of GM-CSF (1000 UI/mL) and IL-4 (200 UI/mL). After another 6 days, iDC were pulsed with thawed irradiated (100 grays) autologous apoptotic blasts (ratio: 1/1 to 1/2) and matured for 24 hours with GM-CSF (1000 UI/mL), IL-4 (200 UI/mL), keyhole limpet hemocyanin (10 μg/mL), TNFa (1000 UI/mL), IL-1 (10 ng/mL) and Prostaglandin E2 (1 μg/mL). Pulsed mature DC (mDC) were frozen in DMSO at 5 × 106 cells/mL after checking sterility.

Treatment

Pulsed mDC were administered at doses of 9 × 106 subcutaneously (SC)(1 mL) and 1 × 106 intra-dermally (0.1 mL). Five doses of vaccine were planned on days +1 + 7 + 14 + 21 and +35 ± 2. No chemotherapy was allowed after vaccination. On day +17, for each patient, a skin biopsy was taken under local anesthesia from the site of the third injection.

Results

• No severe adverse event was documented during and after the treatment.
• The median duration of response from CR and from first vaccine was 157 (range: 125–264) and 132 days (range: 38–165), respectively. Two patients relapsed before day+60. At this time, the three other patients were in persistent CR with undetectable minimal residual disease evaluated by flow cytometry.• The median overall survival (OS) from CR was 472 days (range: 169–973). Although all patients died of relapse, the median OS from pre-inclusion was 147,5 days (range: 27–730) for patients not achieving CR (n = 16) and 509 days (range: 271–1003) for the 5 vaccinated CR patients.

Conclusion

Immunotherapy with autologous leukemic apoptotic corpse-pulsed dendritic cells was found to be a promising candidate for treatment of AML in elderly patients.

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Scientific article publishing date 6/21/2021

Immucura identifier BSC21_272EN

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