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. 2022 Aug 25;39(3):196-203.
doi: 10.4274/tjh.galenos.2022.2022-0024. Epub 2022 May 27.

Predictive Factors for Molecular Response in Chronic Myeloid Leukemia: Reduction Ratio and Halving Time of BCR::ABL1 IS Transcript Levels

Funda Ceran  1 , Sema Akıncı  1 , Mehmet Ali Uçar  2 , Gülten Korkmaz  1 , Mehmet Gündüz  3 , Büşranur Çavdarlı  4 , Şule Mine Bakanay  1 , Mesude Falay  5 , Simten Dağdaş  1 , İmdat Dilek  1 , Gülsüm Özet  1
Affiliations

Predictive Factors for Molecular Response in Chronic Myeloid Leukemia: Reduction Ratio and Halving Time of BCR::ABL1 IS Transcript Levels

Funda Ceran et al. Turk J Haematol. .

Abstract
in English, Turkish

Objective: Achieving an early molecular response (EMR) is crucial for improving the prognosis of patients with chronic myeloid leukemia (CML). The halving time (HT) and reduction ratio (RR) of BCR::ABL1 transcript levels have recently emerged as additional prognostic indexes besides the BCR::ABL1 International Scale (IS). We aimed to investigate the prognostic role of BCR::ABL1 transcript levels, HT, and RR on molecular response kinetics at 3 months in patients with newly diagnosed chronic-phase (CP)-CML.

Materials and methods: Forty patients with CP-CML who received first-line imatinib treatment were included in this study. BCR::ABL1 transcript levels and molecular responses at baseline and at 3, 6, 12, and 24 months of treatment were evaluated retrospectively. Major molecular response (MMR) at 12 months and event-free survival (EFS) were determined as primary endpoints and the effects of treatment kinetics on these parameters were examined.

Results: Of the 40 patients, BCR::ABL1 IS was ≤10% at 3 months in 72.5%, representing EMR. The rate of event occurrence was 45.5% in patients with BCR::ABL1 IS of >10%, whereas it was 6.9% in those with BCR::ABL1 IS of ≤10% (p=0.004). MMR was detected in 62.1% of the patients with EMR and in 9.1% of those without EMR (p=0.003). The cut-off value for achieving MMR was 24 days for HT and 0.04 for RR. Deep molecular response (DMR) at 24 months was associated with HT of ≤24 days and RR of ≤0.04. EFS was found to be significantly better in the group with BCR::ABL1 IS of ≤10% and HT of ≤24 days (p=0.001) and in the group with BCR::ABL1 IS of ≤10% and RR of ≤0.04 (p=0.007) compared to others.

Conclusion: Our findings revealed that MMR could be predicted via EMR as well as by HT and RR. Additionally, HT of ≤24 days and RR of ≤0.04 were more important than BCR::ABL1 IS of ≤10% in achieving DMR at 24 months, and the combination of BCR::ABL1 IS of ≤10% with both HT of ≤24 days and RR of ≤0.04 has the best predictive value for EFS.

Amaç: Kronik myeloid lösemili (KML) hastaların prognozunu iyileştirmek için erken moleküler yanıtın (EMR) elde edilmesi çok önemlidir. Son zamanlarda BCR::ABL1 IS değerinin yanı sıra yarılanma zamanı (HT) ve azalma oranı (RR) gibi kavramlar ek prognostik göstergeler olarak ortaya çıkmıştır. Bu çalışmada yeni tanı kronik faz (KF)-KML hastalarında 3 ayda BCR::ABL1 IS transkript düzeyi, HT ve RR ile moleküler yanıt kinetiklerinin prognostik rolünü araştırmayı amaçladık.

Gereç ve yöntemler: Birinci basamak imatinib tedavisi alan KF-KML’li kırk hasta bu çalışmaya dahil edildi. Bazal, 3, 6, 12 ve 24 aylardaki BCR::ABL1 transkript seviyeleri ve moleküler yanıtlar retrospektif olarak değerlendirildi. On ikinci ay majör moleküler yanıt (MMR) ve olaysız sağkalım (EFS) sonlanım noktaları olarak belirlendi ve bu parametreler üzerindeki tedavi kinetiklerinin etkileri incelendi.

Bulgular: Kırk KF-KML hastasının %72,5’inde 3. ayda BCR::ABL1 IS ≤ %10’du (EMR). Üçüncü ayda BCR::ABL1 IS>%10 olanların %45,5 inde olay varken, ≤%10 olanların %6,9’u olaya sahipti (p=0,004). EMR elde edilen hastaların %62,1’inde, elde edilemeyenlerin %9,1’inde MMR saptandı (p=0,003). Bu çalışmada MMR sağlanmasında eşik değeri HT için 24 gün ve RR için 0,04 olarak saptandı. Yirmi dördüncü ay derin moleküler yanıt (DMR), HT ≤24 gün ve RR ≤0,04 olmasıyla ilişkiliydi. BCR::ABL1 IS ≤%10 ve HT ≤24 gün olan grupta (p=0,001) ve BCR::ABL1 IS ≤%10 ve RR ≤0,04 olan grupta (p=0,007) diğer gruplara göre EFS belirgin olarak daha iyi bulundu.

Sonuç: Bulgularımız, MMR’nin, EMR’nin yanı sıra HT ve RR ile de tahmin edilebileceğini gösterdi. Ayrıca, HT ≤24 gün ve RR ≤0,04 olması 24. ay DMR elde edilmesinde BCR::ABL1 IS ≤%10 olmasından daha önemliydi ve BCR::ABL1 IS ≤%10 olmasının hem HT ≤24 gün hem de RR ≤0,04 ile kombinasyonu, EFS için en iyi belirleyici değere sahipti.

Keywords: Chronic myeloid leukemia; BCR::ABL1 IS; Halving time; Reduction ratio; Molecular response.

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Conflict of interest statement

Conflict of Interest: No conflict of interest was declared by the authors.

Figures

Figure 1
Figure 1
(A) Cumulative molecular response rates according to BCR::ABL1 International Scale (IS), reduction ratio (RR), and halving time (HT) cut-off values. (B) Cumulative incidence graphs for major molecular response (MMR) and deep molecular response (DMR). Non-chronic myeloid leukemia-related deaths and temporary interruptions of imatinib due to toxicity were considered as competing risks in the analysis.
Figure 2
Figure 2
Patients were divided into three groups based on the combined evaluation of BCR::ABL1 International Scale (IS) transcript levels and halving time (HT) and reduction ratio (RR). Event-free survival (EFS) analysis was performed based on these groups.
See this image and copyright information in PMC

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