AJH: Clinical outcomes of MRD recurrence and role of therapeutic interventions after MRD-negative remission in AML patients

For patients with acute myeloid leukemia (AML), the cure rate is only 40-50% even if complete remission (CR) can be achieved after first-line therapy, confirming that many patients may have persistent residual lesions

While several studies have evaluated the kinetics of MRD clearance under first-line treatment and its relevance to clinical outcomes, none have systematically assessed the effect of MRD recurrence on prognosis in patients with AML after initially achieving AND-negative remission; Understanding the outcomes of AML patients with MRD recurrence can not only inform the prognosis of these patients, but also guide treatment decisions

To address these concerns, Professor Nicholas J.

Research results

The included patients received first-line AML treatment at MD Anderson Cancer Center with CR or CRi as the optimal response and MRD-negative by multiparametric flow cytometry (MFC) at the time of the first response, and the authors evaluated MRD recurrence

The study flowchart is shown in Figure 1A

Of the 740 AML patients who first achieved an MRD-negative response between August 2011 and July 2021, 55 patients (7.

The median to morphological recurrence time in patients with MRD recurrence was 5.

It is worth noting that the risk of recurrence in the first 6 months is particularly high, with 42% of patients having relapsed

Median RFS in patients at high risk of cytogenetics was significantly lower than in patients without high-risk karyotype (2.

Os in patients receiving intensive therapy was significantly higher than in patients receiving low-intensity therapy (median OS 36.

The duration from the last MRD-negative bone marrow to MRD recurrence does not affect RFS or OS (figure below

There was no difference

The figure below shows the interventions and patient distribution

Of the 16 patients who changed treatment at the time of MRD recurrence, the median time to treatment intervention was 1.

In addition, there was no difference in survival outcome between patients who received allo-SCT directly at the time of MRD recurrence and those who changed their chemotherapy regimen (figure below

Overall, 12 patients received allo-SCT when they were still in the first morphological remission after MRD recurrence (9 were transplanted directly after MRD recurrence and 3 were transplanted after receiving a new chemotherapy regimen

discuss

MRD is a strong prognostic factor for patients receiving AML on first-line therapy, with 5-year RFS and OS rate estimates of 25% and 34%
in MRD-positive patients, respectively.
This study specifically analyzed outcomes in patients with MRD recurrence after initial MRD-negative response and found that these patients had very poor outcomes, with estimated 5-year RFS and OS rates of 6% and 22%, respectively, significantly lower than historical expectations in patients with persistent MRD, suggesting that MRD recurrence in AML may mean that many patients are about to relapse
.

Mr.
D recurrence was observed in 55 patients (7.
4% of all MRD-negative patients), but a relatively small proportion of patients who found MRD recurrence prior to morphological recurrence may be due to a lack of frequent MRD monitoring (usually every 3-6 months in clinical practice) and the rapid kinetics of recurrence in many cases, particularly in patients
with high-risk cellular molecular features.

More than 40% of patients in this study had MRD recurrence within 3 months of recurrence, suggesting that very frequent MRD monitoring is required prior to morphological recurrence to reliably identify MRD recurrence
.
However, the current consensus does not provide specific guidance on the frequency of MRD assessment when using MFC MRD, and this data suggest that MRD monitoring may be required at least every 3 months in the first year after the first MRD-negative response to reliably detect MRD recurrence
.

This study also supports
MRD-targeted interventions in patients with MRD recurrence after an initial MRD-negative response.
In the boundary marker analysis, patients who received treatment changes (direct change to allo-SCT or change of chemotherapy regimen, with or without follow-up allo-SCT) had better RFS and OS than patients who continued to receive the same treatment regimen, with a 5-year RFS rate of 31%, indicating that treatment interventions enabled a significant proportion of patients with MRD relapses to achieve durable remission
.

In summary, the authors found that patients with AML who had MRD recurrence after an initial MRD-negative response had very high recurrence rates and low
survival rates.
Therapeutic interventions through treatment changes and/or allo-SCT can improve outcomes in these patients and may allow for lasting remission in some patients; Conversely, relapse
almost universally in patients who continue the same treatment without receiving allo-SCT.
These data suggest that frequent MRD monitoring should be performed in patients receiving first-line AML therapy to identify early which patients who are about to relapse may benefit
from MRD targeting strategies.

References

Nicholas J Short,et al.
Clinical outcomes and impact of therapeutic intervention in patients with acute myeloid leukemia who experience MRD recurrence following MRD-negative remission.
Am J Hematol .
2022 Aug 24.
doi: 10.
1002/ajh.
26698.

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