Abstract 3626: Day 21 early bone marrow response does not offer high concordance with response bone marrow in the induction chemotherapy setting of FLT3 mutant acute myeloid leukemia
Authors: Lok Vincent , Hahn Su Bin , Shah Nikesh N. , Kerr Daniel A. , Borrello Ivan M. , Sotomayor Eduardo M. , Swoboda David M. 
Published: March 2024

Purpose: Day 14 early bone marrow biopsies are routinely initiated to determine need for reinduction chemotherapy, but poorly predict true response and risk overtreatment. Day 21 (D21) bone marrow biopsies have been performed in the context of trials utilizing FLT3-targeted therapies in combination with induction chemotherapy (Stone et al. NEJM 2017). However, the utility of D21 bone marrow responses is not well defined.

Methods: We retrospectively identified 26 newly diagnosed FLT3 mutant AML patients who underwent induction chemotherapy with midostaurin and Next Generation Sequencing (NGS) of bone marrow aspirate within a week of diagnosis.

Results: 19/26 (73%) of patients had both D21 and response bone marrow biopsy. Of the remaining 7 patients, 4 patients did not have D21 bone marrow, 2 died of unrelated complications prior to response bone marrow, and 1 did not have recovery marrow available for assessment. Our cohort included 13 (50%) men with a median age of 57 years (range, 21 - 73 years). All patients had ECOG of 0 - 1. 96% of cases were de novo AML and 81% had normal cytogenetics. FLT3 ITD mutations were detected in 17 (65%) patients with a median FLT3 ITD ratio of 0.305 (range, 0.03 - 1) and median FLT3 VAF of 23.8% (range, 3.2 - 80.6%). 7 patients (26.9%) underwent additional allogeneic stem cell transplant.

In the 19 patients evaluable for analysis, 13/13 (100%) patients with blast % ≤ 5 at D21 achieved a complete response (CR) based on recovery marrow. 4/6 (67%) patients with blast % &gt; 5 at D21 which were considered to have residual disease based on pathology review (median blast % 11 (range, 6 - 17%) ultimately achieved a CR. The 2 patients that did not achieve a CR has a blast % of 29% and 9% on D21 marrow. Thus, the positive predictive value of D21 early bone marrow response corresponding with the response bone marrow was only 33% in our patient cohort. Of the 4 patients that did not have D21 marrow but had recovery marrows available for review, the CR rate was 100%.

No other significant differences in initial disease characteristics were seen. There were no differences proportion of co-mutations in NPM1, DNMT3A, TP53, IDH2, and IDH1, and higher FLT3 ITD ratio nor FLT3 VAF corresponded with ability to clear D21 bone marrow. Additionally, there were no differences in minimal residual disease (MRD) and overall survival (OS) between the groups.

Conclusions: Our study suggests early bone marrow response in the context of FLT3-mutant disease is not dependent on inherent disease characteristics and does not correspond to overall response to targeted induction chemotherapy. The utility of these marrows in is this population needs to be studied further in a larger cohort to better understand the clinical necessity to avoid unnecessary cost/procedures to patients and even more importantly unnecessary reinductions.

Citation Format: Vincent Lok, Su Bin Hahn, Nikesh N. Shah, Daniel A. Kerr, Ivan M. Borrello, Eduardo M. Sotomayor, David M. Swoboda. Day 21 early bone marrow response does not offer high concordance with response bone marrow in the induction chemotherapy setting of FLT3 mutant acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3626.