Summary Patients with myelofibrosis (MF) have significant debilitating symptoms, physical disabilities, and poor health‐related quality of life (HRQoL). Here, we report post‐hoc analyses of the impact of ruxolitinib, a potent and selective JAK1 and JAK2 inhibitor, on disease‐related symptoms and HRQoL in MF patients from the large phase 3 COMFORT‐II study (N = 219). During the follow‐up period of 48 weeks, HRQoL and MF‐associated symptoms improved from baseline for ruxolitinib‐treated patients but remained the same or worsened for best available therapy (BAT)‐treated patients. Based on the European Organization for Research and Treatment of Cancer QoL Questionnaire core 30 items (EORTC QLQ‐C30), treatment‐induced differences in physical and role functioning, fatigue, and appetite loss significantly favoured ruxolitinib versus BAT from week 8 (P < 0·05) up to week 48 (P < 0·05). Ruxolitinib resulted in significantly higher response rates in global health status/QoL and Functional Assessment of Cancer Therapy‐Lymphoma (FACT‐Lym) summary scores versus BAT at most time points (P < 0·05). Significant improvements in the Lymphoma subscale (including symptoms of pain, fever, itching, fatigue, weight loss, loss of appetite, and other patient concerns), FACT‐General, FACT‐Lym trial outcome index, and FACT‐Lym total were also observed with ruxolitinib versus BAT starting at week 8 and continuing thereafter. Overall, these data demonstrated that ruxolitinib improved HRQoL in MF patients and further support the use of ruxolitinib for the treatment of symptomatic MF.
Background: With effective tyrosine kinase inhibitor (TKI) therapy, CML-CP disease burden can be reduced to minimal levels, and pts with CML-CP can have a life expectancy similar to that of the general population. Current guidelines recommend that pts continue TKI therapy indefinitely; however, in clinical trials (eg, the Stop Imatinib trials), some pts with deep molecular responses were able to suspend therapy and remain in TFR. This qualitative study assessed pt perspectives on CML treatment and TFR. Methods: Adults with CML-CP were recruited via third-party panels and interviewed by telephone (≈ 45 min) by trained staff from Oxford Outcomes using a standardized semistructured interview guide and open-ended questions. Some questions were not asked in all interviews; reported data are based on pts with responses for the indicated topic. Key themes and perceptions about TFR and potential impacts on health-related quality of life were identified by thematic analysis. Basic demographic information was also collected. Results: Of 40 participants, 68% were female and 68% were < 60 y old. Mean ± SD time since CML diagnosis was 5.2 y ± 4.6 y. Current CML treatment was imatinib (53%), dasatinib (25%), nilotinib (15%), or ponatinib (3%); 33% of pts were receiving second- or later-line TKI therapy; others were not receiving therapy due to a physician-supervised medication holiday (3%) or pregnancy (3%). Frequency of blood work (hematology/chemistry and/or molecular monitoring) for CML was every 3 mo for 60% of pts; 23% and 18% of pts had more frequent or less frequent blood work, respectively. Approximately half of pts (55%) had been told they achieved complete molecular response (CMR). Most pts (85%) did not experience/expect any positive physical impacts of CMR, but 68% said it would provide peace of mind that their CML was not progressing. Pts reported a variety of negative impacts of CML treatment, including financial burden (53%), limited ability to perform normal activities (social activities [25%], hobbies/physical activities [18%], work productivity [15%], and/or housework [10%]), and concern about long-term effects on their physical well-being (23%); 35% of pts reported low or no impact of CML treatment on their daily lives. Most pts (75%) reported having medication side effects, most commonly fatigue (60%), bone/joint pain (28%), nausea (18%), and active bowels/gastrointestinal issues (15%). Most pts (77%) said they had some understanding of TFR, and 58% were cautiously positive about attempting TFR. If their physician recommended it, 77% of pts ≥ 60 y old and 52% of pts < 60 y old said they would consider attempting TFR. The most frequently expressed expected positive impacts of TFR were relief of medication side effects (75%), reduced financial burden (58%), convenience (43%), positive emotional impact (43%), and increased activity level (30%). The most frequently expressed concerns about TFR included fear of resistance to therapy upon relapse (90%), low chance of successfully maintaining TFR (45%), emotional response to relapse and re-initiation of therapy (35%), desire for more frequent disease monitoring (33%), and fear of severe side effects upon re-initiation of therapy (33%). Some pts (28%) said their families may not want them to risk their health by attempting TFR. Among pts < 60 y old, 15% expressed concerns about the well-being of dependent children if they were to attempt TFR and relapse. Pts expressed a desire for more long-term data evaluating the safety of TFR in clinical trials. Pts reported a willingness to attempt TFR if there was at least a 10% chance of sustaining TFR for 2 y (range, 10%-100%), and the shortest duration of TFR they found acceptable ranged from “any amount of time” to 7 y. Conclusions: In this qualitative study, pts perceived many potential positive impacts of TFR, with relief of medication side effects being the most frequently expressed. Although TFR clinical trials have shown high rates of response to re-initiation of TKI therapy in pts with molecular relapse, a perceived risk of developing resistance to therapy was the most notable pt concern about TFR, and pts felt more clinical data are needed. Pt responses also revealed the importance of considering family when discussing TFR. With effective education and in the context of a controlled clinical trial, TFR may be an appropriate goal associated with meaningful pt benefits. More research into the pt perspective on TFR is needed. Disclosures Boquimpani: Bristol Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau. Off Label Use: Current CML treatment recommendations indicate that BCR-ABL TKI therapy should be administered indefinitely, and treatment-free remission (TFR) is an investigational approach that falls outside of current BCR-ABL TKI labels. However, this concept is not new, and promising preliminary results from several clinical trials of TFR have been reported. This abstract does not include any clinical data, but focuses on patient preferences and perceptions of TFR. . Szczudlo:Novartis: Employment, Equity Ownership. Mendelson:Novartis: Employment, Equity Ownership. Benjamin:Novartis Pharmaceuticals Corporation: Consultancy. Masszi:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees.
795FN2 Background: Ruxolitinib (INC424), a potent and selective oral JAK1 and JAK2 inhibitor, demonstrated rapid and durable reductions in splenomegaly and improved disease-related symptoms, role functioning, and quality of life (QoL) in 2 phase 3 studies in patients with myelofibrosis (MF) (the COMFORT studies). Per-protocol, patient-reported, health-related QoL (HRQoL) and symptoms analyses in the COMFORT-II study are limited. Here we report on additional post hoc analyses of these outcomes. The COMFORT-II study includes 219 patients (ruxolitinib, n=146; best available therapy [BAT], n=73). At entry, all patients were classified into intermediate 2-risk or high-risk prognostic groups (Cervantes F, et al. Blood, 2009;113(13):2895-2901) and had palpable splenomegaly ≥5 cm below the costal margin. Patients could have received prior therapy for MF. On BAT, doses and schedules or no therapy were selected by the investigator; therapy adjustments were permitted during the randomized treatment phase at the investigator's discretion. Patients in both arms continued in the randomized treatment phase as long as there was no protocol-defined disease progression. Methods: The European Organisation for the Research and Treatment of Cancer (EORTC) QoL Questionnaire–Core 30 (QLQ-C30) and Functional Assessment of Cancer Therapy–Lymphoma (FACT-Lym) questionnaires were assessed at baseline and weeks 8, 16, 24, and 48. EORTC QLQ-C30 consists of 30 items combined into 15 subscales (Global Health Status/QoL, 5 functioning subscales, and 9 symptom subscales; scores range from 0 to 100, and higher scores indicate better HRQoL and functioning but a worsening of symptoms). FACT-Lym consists of 42 items combined into 8 subscales (4 well-being subscales; 1 symptom subscale [LymS]; and 3 total scale scores: FACT-General [G], FACT-Lym trial outcome index [TOI], and FACT-Lym total; scores for the different subscales vary from 0–28 to 0–168, and higher scores indicate better outcomes). This analysis includes evaluable patients in the randomized treatment phase and assesses changes from baseline in HRQoL and MF symptom scores, including the EORTC subscales, LymS, and FACT total scores, which incorporate well-being and/or symptom subscales. Mixed-model analyses, adjusted for age, sex, baseline score, and prognostic risk category, are used to evaluate treatment differences at each time point and overall across time. Results: HRQoL and MF symptoms, on average, improved compared with baseline for patients receiving ruxolitinib, but remained the same or worsened for patients receiving BAT. Based on the EORTC QLQ-C30, the treatment differences in physical functioning, role functioning, fatigue, and appetite loss significantly favored ruxolitinib starting at week 8 (P <.05) and remained significant at week 48 (P <.05). The overall between-treatment differences (on average across time) in adjusted mean change from baseline for MF symptom scores (95% confidence interval) were: Fatigue, –10.2 (–15.9, –4.5; P <.001); Dyspnea, –11.6 (–17.6, –5.6; P <.001); Appetite loss, –16.3 (–21.5, –11.1; P <.0001); Insomnia, –9.8 (–16.7, –3.0; P <.01); and Pain, –9.0 (–14.9, –3.0), P <.01); negative values favor ruxolitinib. Global Health Status/QoL (Figure) was significantly improved in the ruxolitinib arm compared with the BAT arm at weeks 8, 16, and 48. Scores on the LymS, which includes symptoms of pain, swelling, fever, night sweats, itching, trouble sleeping, fatigue, weight loss, loss of appetite, trouble concentrating, and other patient concerns, also improved significantly during treatment (Figure). Additionally, FACT-G, FACT-Lym TOI, and FACT-Lym total scores were all significantly (P <.05) improved for patients receiving ruxolitinib treatment compared with BAT. Most EORTC QLQ-C30 and FACT-Lym scores improved significantly on ruxolitinib compared with BAT. The treatment effect between the high-risk and intermediate 2-risk prognostic groups was not significantly different based on an analysis of the risk group–by–treatment interaction. Conclusions: These additional analyses from the COMFORT-II study further support that ruxolitinib significantly improves overall HRQoL and MF symptoms compared with BAT. Disclosures: Harrison: Novartis: Honoraria; Incyte: Honoraria; S*Bio: Honoraria; Celgene: Honoraria; Sanofi Aventis: Honoraria. Kiladjian:Novartis: Honoraria; Celgene: Honoraria. Gisslinger:Novartis: Speakers Bureau; Celgene Austria: Research Funding, Speakers Bureau; Aop-Orphan: Speakers Bureau. Knoops:Novartis: Consultancy. Waltzman:Novartis: Employment. Mendelson:Novartis: Employment, Equity Ownership. Zhou:RTI-HS: Employment; Novartis: Research Funding. Copley-Merriman:RTI-HS: Employment; Novartis: Research Funding. Hunter:Incyte Corporation: Employment, Equity Ownership. Levy:Incyte Corporation: Employment, Equity Ownership. Cervantes:Bristol-Myers-Squibb: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Passamonti:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Vannucchi:Novartis: Honoraria. Barosi:Novartis: Consultancy.
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