EHA Library - The official digital education library of European Hematology Association (EHA)

Abstract: PB1835

Type: Publication Only

Background
Studies on CML in last decade have correlated early molecular response (EMR) both at 3/ 6 months and velocity of BCR-ABL reduction with MMR at 18 months. But, this requires molecular monitoring at 3 monthly interval to the least till the achievement of MMR as per NCCN/ELN guidelines. For studying velocity of fall, the molecular monitoring is required at further greater frequency. In resource constraint settings, it is very difficult to monitor patient with qPCR for BCR-ABL transcripts at regular interval owing to the poor educational status, financial constraints, logistic issues (non-availability of testing facilities at all places) and lack of standardization at various labs. Considering these limitations, it is very essential to identify surrogate markers which are universally available for predicting MMR at 18 months

Aims
To study the role of CHR as a surrogate for MMR at 12 and 18 months in resource constraint settings in patients unable to afford frequent molecular monitoring

Methods
Study Design: It’s a prospective single center observational study from northern India. This is part of PRICE study (PGIMER Real world Indian CML Experience) registered vide UTN U1111-1177-8918 and under registration in CTRI.Patients: As part of this study a total of 230 CML patients were screened prospectively attending Adult Hematology Clinic of the host institution. All patients (age>12 years) who were fulfilling the diagnostic criteria of CML-CP before initiation of imatinib therapy were included in the study. Exclusion criteria were either (a) patients in accelerated phase and blast crisis or (b) patients in whom Imatinib was discontinued due to hypersensitivity/ intolerant.Protocol: As part of this study protocol, all newly diagnosed cases of CML-CP were managed with TKI therapy with regular molecular monitoring (3, 6, 12, 18 and 24 months). Patients were initially evaluated with complete hemogram, bone marrow analysis and diagnosis was then confirmed with qualitative molecular test to detect the presence of BCR-ABL translocation. Sokal, Hasford and EUTOS scores were calculated at baseline. Imatinib, was started  and Clinical examination and hemogram was done at weekly intervals to assess for complete hematological remission. Molecular responses at 3, 6 months for EMR and 12, 18 months for MMR was monitored in all these patients.  

Results
85.1 % patients achieved CHR within 12 weeks with median time to achieve CHR being 40 days. Median time to achieve CHR was longer in female patients (42 days) as compared to male patients(36 days), difference was not statistically significant (p=0.636). Patients who achieved MMR at 12 months had a mean CHR duration of 42 days (SD-437.79, n=73) and the patients who didn’t achieve MMR at 12 months the mean duration of CHR was 62.81 days (SD-55.8, n=69). The difference was statistically significant (p=0.01). We also compared the duration of CHR with MMR at 18 months. The patients who achieved MMR at 18 months had a mean CHR duration of 35.45 days (SD-25.41 n=56) and among the patients who didn’t achieve MMR at 18 months the mean duration of CHR was 56.71 days (SD-59.6, n=28). The difference was again significant with p value of 0.024. 

Categories of MR	Groups	n	Days to achieve CHR	P value
EMR at 3 months	BCR/ABL < 10%	159	46.79	<0.001
	BCR/ABL > 10%	32	81.34
OMR at 6 months	BCR/ABL < 1%	113	46.11	0.02
	BCR/ABL > 1%	77	64.16
MMR at 12 months	BCR/ABL < 0.1%	69	39.16	0.001
	BCR/ABL > 0.1%	69	62.81
MMR at 18 months	BCR/ABL < 0.1%	56	35.45	0.024
	BCR/ABL > 0.1%	28	56.71

  

Conclusion
CHR is a good marker to predict the disease response in patients with CML on therapy. 

Session topic: E-poster

Keyword(s): Imatinib