DEFINITION OF PARTIAL RESPONSE IN YOUNGER AML PATIENTS AFTER FIRST INDUCTION COURSE MAY BE EXTENDED BY INCLUSION OF IMMUNOPHENOTYPIC DETECTION OF MEASURABLE RESIDUAL DISEASE IN CR
Author(s): ,
Sylvie Freeman
Affiliations:
Institute of Immunology and Immunotherapy,University of Birmingham,Birmingham,United Kingdom
,
David Grimwade
Affiliations:
King's College London School of Medicine,London,United Kingdom
,
Robert K Hills
Affiliations:
Centre for Trials Research,Cardiff University,Cardiff,United Kingdom
,
Paul Virgo
Affiliations:
North Bristol NHS Trust,Bristol,United Kingdom
,
Naeem Khan
Affiliations:
Institute of Immunology and Immunotherapy,University of Birmingham,Birmingham,United Kingdom
,
Steve Couzens
Affiliations:
University Hospital of Wales,Cardiff,United Kingdom
,
Amanda F Gilkes
Affiliations:
Cardiff University School of Medicine,Cardiff,United Kingdom
,
Ian Thomas
Affiliations:
Centre for Trials Research,Cardiff University,Cardiff,United Kingdom
,
Alan K Burnett
Affiliations:
Isle of Arran,Isle of Arran,United Kingdom
Nigel H Russell
Affiliations:
Nottingham University Hospital,Nottingham,United Kingdom
EHA Library. Freeman S. Jun 23, 2017; 181401; S114
Sylvia Freeman
Sylvia Freeman
Contributions
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Abstract

Abstract: S114

Type: Oral Presentation

Presentation during EHA22: On Friday, June 23, 2017 from 12:30 - 12:45

Location: Hall C

Background

In AML response by morphology after a first cycle of induction therapy is used to guide further therapy including second cycles of induction and choice of consolidation. It is still uncertain how the quality of response post cycle 1 with inclusion of MRD assessment impacts on outcomes within AML risk subgroups including NPM1 wild type standard risk and whether this adds information to MRD status in CR  post cycle 2.  

Aims

To quantify the effect of MRD positivity for response after each cycle of induction therapy in younger patients with AML.

Methods

As part of the UK NCRI AML17 trial (ISRCTN: 55675535) for patients with AML or high risk MDS up to the age of 60, prospective flow cytometric MRD (MFC-MRD) monitoring was performed after each course of induction.  Any level of MRD detected was considered MRD+ (sensitivity thresholds: ~0.02% by tracking diagnostic leukemic aberrant phenotypes /LAIP, ~0.05-0.1% by “different-from normal” blast LAIP). Clinicians were not informed of MFC-MRD results. Following their first cycle of induction with daunorubicin/ara-C based therapy, patients were allocated a risk group by a validated score (comprising cytogenetics, WBC, age, secondary disease, blast response to cycle 1 and mutation status). Poor risk patients received intensified therapy in cycle 2 with a view of proceeding to SCT.

Results

MFC-MRD results after either induction course are available for 1555 patients randomised from 4/09-12/14 (median age 51, range 0-73). Cycle 1 (C1) response data with MFC-MRD was available for 1,400 patients. 70% achieved morphological CR at this time-point; 14% had resistant disease (RD) and 16% were in partial remission (PR) according to clinician. Of patients in CR (n=984) 56% had detectable MFC-MRD (MRD+). Excluding poor-risk patients 14% of patients did not achieve CR (7% RD, 7% PR), 51% of patients in CR were MRD+.  5 year OS for MRD- vs MRD+ vs PR vs RD were 63% vs 44% vs 37% vs 25% for all patients; 69% vs 51% vs 50% vs 30% excluding poor risk patients and 66% vs 49% vs 49% vs 30% for standard risk alone (Figure). The similar OS in this group between CR MRD+ and PR at C1 was maintained in NPM1wt standard risk patients and if censored at stem cell transplant.  
771 patients were in CR post cycle 2 (C2) and provided MFC-MRD data. As expected, there were significant differences in 5 year OS between CR MFC MRD+ vs CR MFC MRD- for all patients (35% vs 63%) and excluding poor-risk (38% vs 70%, n=512). Importantly post cycle 2 MFC-MRD status also differentiated OS for NPM1wt standard risk patients with 5 year OS of 32% vs 64% (P=0.002) for MRD+ vs MRD- (Figure). In stratified analyses, there was some evidence that the effect of MRD positivity on OS was lower in poor-risk patients (test for trend p=0.02 for both C1 and C2). The effect of MFC-MRD status on relapse and OS appeared greater at C2 (relapse, OR 2.00(1.56- 2.55), p<0.001; survival, OR 1.80(1.42-2.28) p<0.001) than C1 (relapse, OR 1.69(1.37- 2.07), p<0.001; survival, OR 1.46(1.19-1.79) p<0.001). In patients with data for both time points, C2 MRD remained significant on OS when adjusting for C1 response. 24 patients converted from C1 MRD- to C2 MRD+, with a poor prognosis (15 relapses, 13 deaths). C1 MRD-/C2 MRD- had the best prognosis.  

Conclusion

MFC-MRD in CR post cycle 1 has similar outcomes to partial remission in younger patients with AML, particularly in patients with good and standard risk disease. Assessment of MFC-MRD post cycle 2 appears to provide additional discrimination to cycle 1: MFC-MRD in courses 1-2 may be useful in further stratifying standard risk patients.

Session topic: 4. Acute myeloid leukemia - Clinical

Keyword(s): Remission, MRD, Induction chemotherapy, AML

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