PS1545 IMPACT OF MOLECULAR RESPONSE ON SURVIVAL AMONG ALLOGENEIC STEM CELL TRANSPLANTATION RECIPIENTS WITH B‐LYMPHOBLASTIC LEUKAEMIA WITH BCR‐ABL1
Authors: Chong S. , Leong T. , Hon S. , Tan S. , Ong T. , Alkudsi S. , Tan J. , Lau N. , Sathar J. , Yegappan S. , Law K. 
Published: June 2019

Background:

Assessment of minimal residual disease (MRD) has emerged as a prognostic tool for patients with acute lymphoblastic leukaemia (ALL). In patients with B‐Lymphoblastic Leukaemia with BCR‐ABL1, MRD assessment can identify patients more likely to benefit from stem cell transplantation (SCT) in first complete remission (CR1). However, the impact of achieving complete molecular response (CMR) in B‐Lymphoblastic Leukaemia with BCR‐ABL1 remains undefined. The addition of immunotherapies and tyrosine kinase inhibitors (TKI) to standard chemotherapy has led to deeper molecular responses, as measured by quantitative polymerase chain reaction of the BCR‐ABL1 transcript, and are associated with improved outcomes. MRD was monitored after induction time point (TP)1, consolidation phase at week 16 (TP2) and end of therapy or pre transplant (TP3).

Aims:

The aim of this study was to investigate the prognostic impact of achieving a complete molecular response (CMR) among our adult B‐Lymphoblastic Leukaemia patients with BCR‐ABL1 with the treatment outcomes in Hospital Ampang, the national tertiary referral centre in Malaysia.

Methods:

Patients above 12 years of age diagnosed at Hospital Ampang between 2007 and 2017 were included in this study. Major molecular response MMR was defined as BCR‐ABL1:ABL1 ratio ≤0.1% on the International Scale for p210 BCR‐ABL1 or a 3‐log reduction in transcripts for p190 BCR‐ABL1. Overall survival (OS) was analysed using Kaplan‐Meier survival function, calculated from the time of treatment initiation till death and divided into 2 groups of BCR‐ABL1:ABL1 ratio ≤0.1% and BCR‐ABL1:ABL1 ratio >0.1%. The different groups were compared using log‐rank test.

Results:

A total of 96 adult patients were identified with median age of diagnosis of 37.5 years old (range from 14 to 69 years old), female predominance (56%), and majority Malay ethnicity (50%). At the time of analysis, 33 (34.4%) patients were alive. The median overall survival (OS) of this cohort was 16.8 months (95%CI: 12.0; 20.9). Median OS was not significantly different (p > 0.05) between those who had achieved major molecular response (MMR) (BCR‐ABL1:ABL1 ratio ≤ 0.1) and those who did not (20.4 months vs 16.8 month) at TP1, those who had achieved MMR at TP2 (35.7 months vs 17.5 months) and those who had additional myeloid markers (13.1 months vs 25.3 months). Median OS was significantly different between patients who achieved MMR at TP3 as compared to those who did not (77.0 months vs 20.4 months, p = 0.006). The risk of dying is 3 times higher for those who did not achieved MMR at TP3 (hazard ratio = 3.0, 95%CI: 1.97; 6.70, p = 0.009) compared to those who had MMR.

Summary/Conclusion:

Achievement of MMR at TP3 prior to allogeneic stem cell transplantation is associated with superior survival outcomes. Prospective trials using MRD‐based risk stratification and to guide treatment decision for B‐Lymphoblastic Leukaemia patients with BCR‐ABL1 may elucidate the optimal post remission management of these patients.