Hypoplastic acute myeloid leukemia in an elderly patient. A long‐term partial remission with low‐dose prednisone and G‐CSF

AbstractThis analysis from the phase II BRIGHT AML 1003 trial reports the long-term efficacy and safety of glasdegib + low-dose cytarabine (LDAC) in patients with acute myeloid leukemia ineligible for intensive chemotherapy. The multicenter, open-label study randomized (2:1) patients to receive glasdegib + LDAC (de novo, n = 38; secondary acute myeloid leukemia, n = 40) or LDAC alone (de novo, n = 18; secondary acute myeloid leukemia, n = 20). At the time of analysis, 90% of patients had died, with the longest follow-up since randomization 36 months. The combination of glasdegib and LDAC conferred superior overall survival (OS) versus LDAC alone; hazard ratio (HR) 0.495; (95% confidence interval [CI] 0.325–0.752); p = 0.0004; median OS was 8.3 versus 4.3 months. Improvement in OS was consistent across cytogenetic risk groups. In a post-hoc subgroup analysis, a survival trend with glasdegib + LDAC was observed in patients with de novo acute myeloid leukemia (HR 0.720; 95% CI 0.395–1.312; p = 0.14; median OS 6.6 vs 4.3 months) and secondary acute myeloid leukemia (HR 0.287; 95% CI 0.151–0.548; p < 0.0001; median OS 9.1 vs 4.1 months). The incidence of adverse events in the glasdegib + LDAC arm decreased after 90 days’ therapy: 83.7% versus 98.7% during the first 90 days. Glasdegib + LDAC versus LDAC alone continued to demonstrate superior OS in patients with acute myeloid leukemia; the clinical benefit with glasdegib + LDAC was particularly prominent in patients with secondary acute myeloid leukemia. ClinicalTrials.gov identifier: NCT01546038.

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Low dose cytosine arabinoside-partial remission of acute myeloid leukemia without evidence of differentiation induction

Pathology ◽

10.1016/s0031-3025(16)38074-6 ◽

1984 ◽

Vol 16 (3) ◽

pp. 364

Author(s):

M. Leyden ◽

A. Manoharan ◽

A. Boyd ◽

Z. Cheng ◽

J. Sullivan

Keyword(s):

Acute Myeloid Leukemia ◽

Cytosine Arabinoside ◽

Partial Remission ◽

Myeloid Leukemia ◽

Low Dose ◽

Differentiation Induction ◽

Acute Myeloid

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PS1029 CLINICAL BENEFIT OF GLASDEGIB PLUS LOW-DOSE CYTARABINE IN PATIENTS WITH DE NOVO AND SECONDARY ACUTE MYELOID LEUKEMIA: LONG-TERM ANALYSIS OF A PHASE 2 RANDOMIZED TRIAL

HemaSphere ◽

10.1097/01.hs9.0000562412.43628.df ◽

2019 ◽

Vol 3 (S1) ◽

pp. 464-465

Author(s):

M. Heuser ◽

W. Fiedler ◽

M.A. Sekeres ◽

P. Montesinos ◽

B. Leber ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Low Dose ◽

De Novo ◽

Phase 2 ◽

Secondary Acute Myeloid Leukemia ◽

Term Analysis ◽

Low Dose Cytarabine ◽

Acute Myeloid

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WT1-targeted dendritic cell vaccination as a postremission treatment to prevent or delay relapse in acute myeloid leukemia.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.2506 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 2506-2506 ◽

Cited By ~ 2

Author(s):

Zwi N. Berneman ◽

Ann Van de Velde ◽

Sebastien Anguille ◽

Nathalie Cools ◽

Ann Van Driessche ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Complete Remission ◽

Partial Remission ◽

Myeloid Leukemia ◽

Residual Disease ◽

Wilms Tumor ◽

Dendritic Cell Vaccination ◽

Clinical Responses ◽

Acute Myeloid

2506 Background: Vaccination with tumor antigen-loaded dendritic cells (DC) holds promise for the adjuvant treatment of cancer. Methods: In a phase I/II trial, we investigated the effect of autologous DC vaccination in 17 patients with acute myeloid leukemia (AML) in remission but at very high risk of full relapse. Wilms’ tumor 1 protein (WT1) was chosen as immunotherapeutic target and introduced into the DC by mRNA electroporation. We are continuing a phase II trial, which is still recruiting. Results: Two out of 3 patients, who were in partial remission with chemotherapy-refractory disease, were brought into complete remission following 4 biweekly intradermal injections of WT1 mRNA-electroporated DC. In those 2 patients as well as in 6 other patients who were in complete remission but who had molecularly demonstrable residual disease, there was a return to normal of the AML-associated WT1 mRNA tumor marker following DC vaccination, compatible with reaching clinical and molecular remission in 8/17 patients. Among the 8 responders, there have been 2 relapses and 2 deaths. Of the 9 non-responders, 8 have relapsed and 7 have died. Of the 2 patients in partial remission who were brought into complete remission by DC vaccination, 1 has died following relapse. Median overall survival was 6 months in non-responders and 52 months in responders (p=0.0007). Median relapse-free survival was 3 months in non-responders as compared to 47 months in responders (p<0.0001). Clinical responses overall were correlated with elevated levels of activated natural killer (NK) cells post-vaccination. Long-term clinical responses, lasting for at least 3 years, were significantly correlated with an increase in polyepitope WT1-specific tetramer+ CD8+ T-cell frequencies. Conclusions: DC-based immunotherapy elicits both innate (NK) and adaptive (T cells) cellular responses correlated with clinical benefit. WT1 mRNA-transfected DC emerge as a feasible and effective strategy to control residual disease in AML, in particular as a post-remission treatment to prevent full relapse.

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