Side-effects Profile and Outcomes of Ponatinib in the Treatment of Chronic Myeloid Leukemia

Ponatinib is associated with cardiovascular adverse events (CAEs), and its frequency in the real world is limited. In this retrospective study, we examined the survival outcomes and associated toxicities in 78 consecutive ponatinib-treated patients with chronic myeloid leukemia (CML) at the Moffitt Cancer Center from January 2011 through December 2017. The most common non-CAE was thrombocytopenia (39.7%), occurring in a dose-dependent fashion. Eighteen patients (23.1%) experienced some form of CAE, with the most common being arrhythmia (9%) and hypertension (7.7%), whereas 3 patients experienced myocardial infarction (3.8%). Before 2014, most patients were started on ponatinib 45 mg daily. There was an inverse correlation between cardio-oncology referral and the number of CAEs (P = .0440); however, a lower ponatinib starting dose, more frequent dose reduction, and increased cardio-oncology referral all were likely to have contributed to the observed decrease in CAEs after 2014. The response rate and 5-year overall survival (OS) were higher than those observed in the Ponatinib Ph+ ALL and CML Evaluation (PACE) trial (major molecular response, 58.7% vs 40% and OS, 76% vs 73%; median follow-up of 32.5 months). Ponatinib-treated patients with chronic phase–CML did not show a significant improvement with allogeneic stem cell transplantation, whereas those with accelerated phase/blast phase–CML had a much better outcome (median OS of 32.9 months vs 9.2 months; P = .01). These results demonstrate that ponatinib is highly effective. Dose adjustments and increased awareness of the cardiotoxicities associated with ponatinib may help maximize its benefits

Fatigue Perpetuating Factors as Mediators of Change in a Cognitive Behavioral Intervention for Targeted Therapy-Related Fatigue in Chronic Myeloid Leukemia: A Pilot Study

BACKGROUND: Cognitive behavioral therapy for targeted-therapy related fatigue (CBT-TTF) has demonstrated preliminary efficacy in reducing fatigue in patients treated with tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML). PURPOSE: The aim of the current analyses was to explore whether fatigue perpetuating factors (disturbed sleep/wake cycle, dysregulated activity patterns, maladaptive cognitions about fatigue and cancer, insufficient processing of cancer and treatment, inadequate social support and interactions, heightened fear of cancer progression) changed over time in patients receiving CBT-TTF, and whether the effect of CBT-TTF on fatigue was mediated by these factors. METHODS: Secondary data analyses were conducted from a pilot randomized controlled trial. Patients with CML treated with a TKI who reported moderate to severe fatigue were randomized 2:1 to CBT-TTF delivered via FaceTime for iPad or a waitlist control condition (WLC). Self-report measures of fatigue and fatigue perpetuating factors were obtained before randomization and post-intervention (i.e., approximately 18 weeks later). Mixed model and mediation analyses using bootstrap methods were used. RESULTS: A total of 36 participants (CBT-TTF n = 22, WLC n = 14) who had baseline and 18-week follow-up data and attended >5 sessions for CBT-TTF were included. Participants randomized to CBT-TTF reported improvements in activity (mental, physical, social, p's ≤ .023) and cognitions (helplessness, catastrophizing, focusing on symptoms, self-efficacy, p's ≤ .003) compared to WLC. Mental activity, social activity, self-efficacy, helplessness, and focusing on symptoms, as well as sleep and insufficient processing (avoidance) mediated the relationship between treatment group and fatigue. CONCLUSIONS: CBT-TTF appears to improve TKI-related fatigue in CML patients through changes in behavior (sleep, activity patterns) and cognitions about fatigue and cancer. A larger randomized controlled trial is warranted to confirm these findings

Survival Outcomes in Blastic Plasmacytoid Dendritic Cell Neoplasm By First-Line Treatment and Stem Cell Transplant

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with dismal clinical outcomes. Conventional chemotherapies were previously shown to have some clinical efficacy, however, long-term outcomes of BPDCN patients remain poor. In a recent clinical trial, SL-401 demonstrated an overall response rate (ORR) of 90% in previously untreated BPDCN patients. Despite promising outcomes observed in SL-401 studies, there remains a lack of data regarding the optimal first-line therapy. In this single institution retrospective study, we explored the survival outcomes based on front-line treatment and allogeneic stem cell transplant (allo-SCT). A total of 49 patients with confirmed diagnosis of BPDCN were included in the study. Median age at diagnosis was 71.4 (32.0-91.4) years with a male predominance (82%). Among these, 11 (22%) patients had concurrent hematologic neoplasms at the time of BPDCN diagnosis. The most common site of disease involvement was skin (n=42, 86%) followed by bone marrow (BM) (n=32, 65%), lymph node (LN) (n=13, 27%), and nasopharynx (n=2, 4%) with 14 (29%) and 5 (10%) patients having skin and BM involvement only, respectively. Of note, 17 (35%) patients had both skin and BM disease and 8 (16%) had simultaneous skin, BM, and LN involvement. In the front-line setting, CHOP-based regimens, hyper-CVAD, and SL-401 were used in 10 (20%), 11 (22%), and 12 (24%) patients, respectively. The median cycle number of SL-401 treatment was 6 (1-73). Allo-SCT was performed in 10 (20%) patients and 4 (8%) patients received autologous stem cell transplant (auto-SCT). Transplant was performed following first-line therapy in 11 patients (CR, n=10; PR, n=1) and second-line therapy in 3 patients (CR, n=3). Among 21 vs. 12 patients who received chemotherapy vs. SL-401 as their first-line therapy, a total of 11 (52%) and 3 (25%) patients underwent transplant. A total of 23 (55%), 13 (31%), and 6 (14%) patients achieved a complete response (CR), partial response (PR), and progressive disease (PD), respectively. CR rate was higher in patients who were treated with hyper-CVAD compared to others, however, it was not statistically significant (50% in CHOP-based regimens vs. 91% in hyper-CVAD, P=0.064; 50% in SL-401 vs. 91% in hyper-CVAD, P=0.069). The median PFS was 9.9 months and the median OS was not reached when all patients were included for the analyses. In the subgroup analyses, patients who were treated with hyper-CVAD had longest PFS compared to patients treated with CHOP-based regimens (HR=0.217, 95%CI=0.050-0.933, P=0.003) or SL-401 (HR=0.385, 95%CI=0.126-1.179, P=0.075) although the PFS difference between hyper-CVAD and SL-401 did not reach the statistical significance. There was no PFS difference between SL-401 and CHOP-based regimen treated groups (HR=0.931, 95%CI=0.321-2.70, P=0.894). In the OS analysis based on first-line therapy, there was no difference between patients treated with SL-401 compared to patients treated with chemotherapy regimens (HR=1.597, 95%CI=0.460-5.548, P=0.431). Further, there was no OS difference between individual types of front-line therapies (P=0.678). In contrast, patients who received allo-SCT showed significantly longer OS outcomes compared to patients with no transplant (HR=0.160, 95%CI=0.0453-0.56, P=0.041). Additional OS analyses based on age (<60 vs. ≥60) (HR=0.481, 95%CI=0.146-1.582, P=0.258), ASXL1 mutation (HR=1.705, 95%CI=0.2773-10.48, P=0.5649), or presence of previous or concurrent hematologic malignancy (HR=2.97, 95%CI=0.65-13.57, P=0.1602) did not show any statistical difference. In a multivariate Cox model (adjusting for age, front-line therapy, gender, and transplant) allo-SCT was significant factor for OS (HR=0.137, 95%CI=0.020-0.959, P=0.045). In conclusion, our study supports current recommendations of using SL-401 or hyper-CVAD as the first-line treatments followed by consolidation with allo-SCT in the eligible responders to induction therapy to further improve survival outcomes in BPDCN patients. Disclosures Lancet: Abbvie: Consultancy; Agios Pharmaceuticals: Consultancy, Honoraria; Astellas Pharma: Consultancy; Celgene: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; ElevateBio Management: Consultancy; Jazz Pharmaceuticals: Consultancy; Pfizer: Consultancy. kharfan-Dabaja:Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy. Sokol:Kyowa/Kirin Inc.: Membership on an entity's Board of Directors or advisory committees; EUSA Pharma: Consultancy, Honoraria, Speakers Bureau; Kymera Therapeutics: Membership on an entity's Board of Directors or advisory committees

Internet-assisted cognitive behavioral intervention for targeted therapy–related fatigue in chronic myeloid leukemia: Results from a pilot randomized trial

Background: Fatigue is a common and disabling side effect of targeted therapies such as tyrosine kinase inhibitors (TKIs) used to treat chronic myeloid leukemia (CML). The goal of the current study was to conduct a pilot randomized trial of the first cognitive behavioral intervention developed for fatigue due to targeted therapy. Methods: Patients with CML treated with a TKI who were reporting moderate to severe fatigue were recruited and randomized 2:1 to cognitive behavioral therapy for targeted therapy–related fatigue (CBT-TTF) delivered via FaceTime for the iPad or to a waitlist control (WLC) group. The outcomes were acceptability, feasibility, and preliminary efficacy for fatigue (Functional Assessment of Chronic Illness Therapy–Fatigue; primary outcome) and quality of life (Functional Assessment of Cancer Therapy–General; secondary outcome). Participants were assessed before randomization and after treatment (ie, approximately 18 weeks later). Results: A total of 44 patients (mean age, 55 years; 48% female) were assigned to CBT-TTF (n = 29) or WLC (n = 15). The study participation rate was 59%. Among the patients assigned to CBT-TTF, 79% completed the intervention. Intent-to-treat analyses indicated that patients assigned to CBT-TTF demonstrated greater improvements in fatigue (d = 1.06; P <.001) and overall quality of life (d = 1.15; P =.005) than those assigned to WLC. More patients randomized to CBT-TTF than WLC demonstrated clinically significant improvements in fatigue (85% vs 29%) and quality of life (88% vs 54%; P values ≤.016). Conclusions: CBT-TTF displays preliminary efficacy in improving fatigue and quality of life among fatigued patients with CML treated with TKIs. The findings suggest that a larger randomized study is warranted