Analysis of Real-world Population of Patients with CML Essential

Real-world patients with chronic myeloid leukemia (CML) are often different from the ones selected for clinical trial inclusion, according to Giorgina Specchia, MD, of the University of Bari, Italy. At the 60th ASH Annual Meeting and Exposition, Specchia presented results on clinical, hematologic characteristics and treatment response all newly diagnosed patients with CML referred to Italian Hematology Centers of the GIMEMA Study Group between January 2012 and November 2018.

For the analysis, the only exclusion criterion was refusal by the patient to participate. All data was recorded in a web-based database and included clinical, hematological, cytogenetic, and biological information. As of November 26, 2018, there were 2,025 patients enrolled.

“We evaluated 1,200 patients with at least 24 months of follow-up,” Specchia said. Recruitment into the study was initially slow, he said, but grew exponentially from 2015 onwards. At this time, 61.5% of patients were male; the median age was 58.5. Of the total 1,096 patients, at diagnosis 1085 (99%) patients were in chronic phase, 8 (0.7%) patients were in accelerated phase and 3 (0.3%) in blastic crisis.

When evaluating patients by risk scores, the majority of patients were found to have intermediate risk when the Sokal Index or EURO was used, but EUTOS found no intermediate risk patients (and an overwhelming majority were low risk). The EUTOS Long-Term Survival (ELTS) score also found most patients were low risk (only 40% were considered intermediate or high risk). Comparatively, 60% of patients were considered intermediate or high risk by Sokal.

“ELTS is more adherent to the biology of the disease,” Specchia said.

At cytogenetic analysis, there were on 982 patients: 889 (90.6%) had no additional cytogenetic aberrations (ACA), 60 (6.1%) had major route ACA, and 33 (3.3%) had minor route ACA.

According to comorbidity and excluding CML diagnosis as a parameter, among 1,158 cases the Charlson comorbidity index was 0, 1, 2 or ≥3 in 910 (78.6%), 127 (11%), 75 (6.4%) and 52 (4.4%) patients, respectively.

When analyzed by type of comorbidity (n=1,200), cardiovascular disease was the most prevalent (26.2%), followed by lung disease (9.7%), and metabolic disease (7%).

“More than 25% had at least one chronic comorbidity, but 8.1% had other cancers already known at diagnosis,” Specchia said. “And note, we were excluding CML as a diagnosis.”

Overall survival (OS) was high, at 95.7% with a median follow-up of 37 months. There were 49 deaths, 12 of which were considered to be related to CML disease progression.

When using the Sokal risk scoring (n=1,010), there was no difference in OS at 4 years among patients with low, intermediate, or high risk (P=0.1193). However, there was a statistically significant difference when using the ELTS risk score (n=1,028) between low (98%), intermediate (94.3%) and high-risk (86.8%;P<0.0001).

Of the tyrosine kinase inhibitors (TKIs) used as first-line therapy, about one-half of the patients (n=593) were on imatinib while the others were treated with a second-generation TKI. Specchia noted that 356 patients had been pretreated with hydroxyurea.

When analyzed by TKI used, OS at 4 years was 93.5% for imatinib and 97.8% for second-generation TKIs. OS at 4 years by ELTS risk found statistically significant differences in patients regardless of which TKI was used.

Molecular response was better with second-generation TKIs than imatinib; this difference was highly pronounced early in treatment (with 23.9% vs 5.5% MR3 response at 3 months between second-generation and imatinib, respectively), he said. Similar results were found with MR4 and MR5 responses as well, Specchia said.

“Our preliminary results of this observational epidemiologic study suggest that collection of clinical data of CML patients treated out of strictly clinical trials represent an essential tool for long-term treatment, [and we are] able to observe setting strategies based on the clinical characteristics, the degree of response obtained, and the toxicity related to the therapy in overall CML population,” Specchia said. “Molecular responses are faster and deeper with second generation TKIs, and while the OS difference was not statistically significant between TKI treatment groups, it became statistically significant in particular for the ELTS intermediate risk group patients.”