PracticeUpdate Conference Series ASH 2018

Smoking LinkedWith Poorer Outcomes In Newly Diagnosed ALL Treated With TKIs Only non-smokers benefited from superior outcome associated with ponatinib. C igarette smoking is associated with poorer outcomes in patients newly diagnosed with Philadelphia chro- cohort, and 67% for the non-smoker cohort (P < .001).

The combination of hyper-CVAD and ponatinib led to superior outcomes, compared with the combination of chemotherapy and either imatinib or dasatinib, but only among non-smokers. Among patients taking imatinib, 5-year CR duration was 49% for smokers and 70% for non-smokers (P = .202). The 5-year OS was 33% for smokers and 50% for non-smokers (P = .218). In patients treated with dasatinib, 5-year CR duration was 50% for smokers and 70% for non-smokers (P = .249), while 5-year OS was 30% for smokers and 59% for non-smokers (P = .013). Finally, among those on ponatinib, 5-year CR duration was 63% for smokers and 93% for non-smokers (P = .018), and 5-year OS was 23% for smokers and 91% for non-smokers (P < .001). Dr. Jabbour and his colleagues identified the presence of central nervous system disease (HR 3.141; 95% CI 1.306–7.553; P = .011), P190 transcript type (HR 0.254; 95% CI 0.113–0.570; P = .001), the achieve- ment of complete molecular response within 3 months of therapy (HR 2.119; 95% CI 1.163–3.860; P = .014), and smoking pack-years (HR 1.014; 95% CI 1.005–1.022; P = .001) as prognostic factors for OS. The cumulative incidence of relapse was 36% in the smoker cohort, compared with 19% among non-smokers (P = .027), while the cumulative incidence of death in CR was 31% with smokers and 17% with non-smokers (P = .011). In addition, each pack-year history of smok- ing prior to diagnosis was associatedwith 1% increase of death in patients with Ph+ ALL. The results of the study led Dr. Jabbour and his colleagues to conclude in their abstract that smoking “is an independent poor prog- nostic factor of outcome in patients treated with chemotherapy and TKI” and that the best outcome was found in non-smokers who were treated with chemotherapy and ponatinib.

mosome-positive acute lymphoblastic leukemia (Ph+ ALL) who are being treated with a combination of intensive chemother- apy and a tyrosine kinase inhibitor (TKI), according to new research presented at ASH 2018. According to the researchers, the idea behind the study was the fact that a prior history of cigarette smoking is known to contribute to poor outcomes in patients with other types of cancer. In addition, it may increase the risk of vascular events, particularly in patients treated with TKIs. The objective of this study was to evaluate the impact of cigarette smoking in patients with newly diagnosed Ph+ ALL who were treated with intensive chemotherapy com- bined with a TKI, as it related to complete response (CR) duration, overall survival (OS), and cumulative incidence of relapse and death in CR. Researchers led by Elias J. Jabbour, MD, of theUniversity of TexasMDAndersonCenter in Houston, analyzed data on 202 patients who were newly diagnosed with Ph+ ALL and who were treated with hyper-CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone) in combination with the TKI imatinib (n=54), dasatinib (n=72) or ponatinib (n=76) between 2001 and 2018. Median follow-up was 77 months. Overall, 82 of the patients were identified as smokers, with a median smoking history of 20 pack-years. Smokers were defined as having 1 pack-year history of smoking before diagnosis. They were also older, more likely to be male, and had worse performance status than the non-smokers. There was also a trend toward non-smok- ers being more likely to receive allogeneic stem cell transplantation (P = .056). There were no differences between smok- ers and non-smokers with respect to rates of CR, negativity of flow cytometry, and complete molecular response. The 5-year CR duration was 53% in the smoker cohort compared with 78% in the non-smoker cohort (P = .006), while the 5-year OS rate was 31% for the smoker

unimportant or not related to their ITP. I think this disconnect between what patients describe and what physicians believe about fatigue occurs for a num- ber of reasons,” she said. “First, there has not been much research up until recently looking at the correlation between fatigue and thrombocytopenia and other auto- immune diseases. Second, physicians tend to address bleeding and bruising symptoms as opposed to something they can’t see or quantify like fatigue. Third, even if doctors accept that fatigue is a real problem in ITP, they don’t know what to do about it.” Ms. Kruse also suggested that the impact of ITP on patient quality of life has been underestimated as well, explaining that patients frequently describe the unpre- dictability and frustration of living with ITP, feeling limited in their life choices and worn out or depressed by the many ups and downs that accompany the condition. “ITP patients’ platelet counts can fluctuate dramatically, typically requiring patients and their families to carefully monitor their platelets to guard against an unexpected drop that might signal a relapse or height- ened risk for serious bleeding,” she said. “People with ITP regularly cite the stress and anxiety associated with watching their numbers. This all has a huge impact on quality of life, ability to work, go to school, travel, and just enjoy life.”

www.practiceupdate.com/c/77030

www.practiceupdate.com/c/77042

ASH 2018 • PRACTICEUPDATE CONFERENCE SERIES 13