Abstract Background: JAK2 inhibitors have been shown to improve symptoms and produce durable reductions in splenomegaly in patients with myelofibrosis (MF), and ruxolitinib has been shown to improve survival in MF patients (Cervantes et al., 2013; Verstovsek et al., 2013). Current prognostic models such as DIPSS plus (Gangat et al., 2011) predict survival in MF based on clinical, laboratory, and cytogenetic information, but their value in predicting clinical response or survival during treatment with JAK2 inhibitors remains unknown. We hypothesized that clinical features such as bone marrow fibrosis and splenomegaly may have independent effects on therapy response. Therefore, we conducted a retrospective analysis to create a new model to risk stratify patients with respect to their likelihood of responding to oral JAK2-inhibitor therapy. Methods: We studied a cohort of 203 patients with bone marrow biopsy-proven MF seen at University of Michigan, Stanford University, and Mayo Clinic in Scottsdale, AZ. These patients were all treated with ruxolitinib or an experimental JAK2 inhibitor. Our primary endpoint was defined as IWG-MRT criteria for splenic response by palpation (Tefferi et al., 2013). Response in patients with spleen size of less than 5 cm was defined as complete resolution of splenomegaly. Of the 203 patients studied, splenic response was evaluated after 3 months of therapy in 167 patients and after 6 months of therapy in 138 patients; 127 patients were in both groups. A logistic regression was performed to identify factors that would predict clinical response. Results: The following characteristics were significantly associated with spleen response at 3 and 6 months: initial spleen size, European consensus criteria grading of MF on bone marrow biopsy, initial DIPSS plus score, and initial WBC count. Cellularity on marrow biopsy was not significant. We enriched a baseline logistic model of initial dose of oral JAK2 therapy and DIPSS plus score with additional prognostic factors. We found the following clinical characteristics to be jointly associated with splenic response: normalized initial dose of oral JAK2 inhibitor, initial spleen size, DIPSS plus score, degree of fibrosis by European consensus criteria. Duration of disease from time of diagnosis to time of treatment initiation was not prognostic for splenic response. We used this model to calculate the probability of splenic response based on a risk score: Risk score = –1.18(Dose) + 0.09(Initial Spleen Size in cm) + 0.20(DIPSS-plus Points) +0.92 (if fibrosis is MF-3). The probability at 6 months can then be calculated from the risk score as follows: [1/(1+e(risk score-2.6))]. The figure demonstrates the prognostic gain of our model over a model based on DIPSS plus alone. Conclusion: With this observational study, we propose a predictive model which may serve as a clinical tool to identify which patients are most likely to benefit from JAK2 inhibitor-based therapies. Further validation in independent data sets will be required before this model can be more widely applied. Disclosures Mesa: Incyte Corporation, CTI, NPS Pharma, Inc., Gilead Science Inc., Celgene: Research Funding. Gotlib:Incyte: Consultancy, Honoraria, Research Funding, Travel Reimbursement Other; Gilead: Research Funding; Sanofi: Research Funding; Novartis: Research Funding, Travel Reimbursement, Travel Reimbursement Other. Talpaz:ARIAD Pharmaceuticals, Inc., BMS, Sanofi, Incyte, Pfizer: Research Funding.
Limitations of fibrosis grade as diagnostic criteria for post polycythemia vera and essential thrombocytosis myelofibrosis.
Journal of Clinical Oncology | March 7, 2019 | Volume: 33 | Issue: 15_suppl | Pages: e18078-e18078
Myeloproliferative neoplasms (MPNs) are rare hematological malignancies with a significant symptom burden often left unresolved despite recent advances in pharmacological therapy. Yoga is a nonpharmacological strategy that has been shown to improve symptoms in other cancers and may be effective for improving symptoms in MPN patients. Online yoga helps address many of the commonly reported barriers of cancer patients to in-person interventions and may make yoga more accessible to MPNs. An exploration of MPN patient perceptions of participation in online yoga is needed to tailor interventions to patient needs and inform future studies. The purpose of this study was to explore the perceptions of MPN patients participating in a 12-week online yoga intervention. This article represents the combined qualitative interview data from two studies. Participants were asked to complete 60 min/wk of online, home-based yoga and were asked to participate in a 15- to 20-minute phone interview postintervention. The qualitative data was coded in NVivo 11 for content analysis. The total sample included 39 MPN patients. Online yoga was well accepted and liked among these patients. They reported physical (eg, improved sleep, reduced fatigue) and mental (eg, reduced stress) health benefits and liked the convenience of being able to do yoga at home. Online yoga provides a feasible and attractive format through which to deliver a nonpharmacological intervention among MPN patients. Randomized controlled trials are needed to confirm the effects of online yoga on MPN patient symptoms. The qualitative findings presented here help inform the development of these future trials.
Predictive models for splenic response to JAK-inhibitor therapy in patients with myelofibrosis
e21704 Background: Patients with myeloproliferative neoplasms (MPN) have difficult symptom burden (i.e. fatigue, pruritus, night sweats) not resolved by current medical therapies including jak inhibitor therapy. We hypothesize that on-line (at home) yoga might alleviate MPN symptoms and complement medical therapy. Methods: MPN patients, recruited by social media, were asked to complete 60 min/week of online yoga (designed for MPN patients) for 12 weeks and completed online self-report surveys (weeks 0,7,12 and 16) on participation (Qualtrics), disease features, and symptom burden (MPN Symptom Assessment Form; NIH PROMIS measures of pain, anxiety, depression, sleep, and sexual function). Results: Two hundred and forty-four MPN patients completed the eligibility survey, 134 were eligible, 55 completed the informed consent, and 38 MPN patients completed the 12-week intervention. The majority of participants were diagnosed with either PV (n = 16) or ET (n = 16), with MF being less common (n = 6). Approximately 37% (n = 14) of study participants averaged ≥60 min/week of yoga (i.e., demand). Yoga participation averaged 50.8±36.2 min/week. Overall, 68% of participants were satisfied with online yoga and 75% felt that is was helpful for coping with MPN-related symptoms (i.e., acceptability, practicality). Additionally, 75% of participants felt safe from injury while participating in online yoga. Only one adverse event was reported (irritated enlarged spleen). From week 0 to week 12 (n = 38), there were significant improvements in total symptom burden (effect size [ES] in standard deviation units = -0.36, p = 0.004), anxiety (ES = -0.67, p = 0.002), depression (ES = -0.41, p = 0.049), sleep (ES = -0.58, p < 0.001), and fatigue (ES = -0.33, p = 0.04). These improvements remained significant at follow-up week 16 (n = 28) for all outcome measures with a trend for maintained fatigue improvement (ES = -0.34, p = 0.06) (see Table 1). There were no significant differences in outcomes between those that averaged < 60 min/week of yoga compared to those that averaged ≥60 min/week of yoga. Conclusions: A 12-week online yoga intervention is feasible (i.e., accepted, practical) for MPN patients and merits a randomized trial as complementary therapy.
Supportive care and symptom burden in patients with myeloproliferative neoplasms.
Journal of Clinical Oncology | September 6, 2018 | Volume: 35 | Issue: 15_suppl | Pages: e21684-e21684
e21684 Background: Pharmacologic therapy stabilizes hematologic counts and splenomegaly in myeloproliferative neoplasms (MPN), however only partial symptom improvement typically occurs. Evidenced-based supportive care interventions are needed, however data is limited in patients with MPNs. Methods: Patients were recruited internationally via social media. Informed consent and online self-report surveys (Qualtrics) were completed capturing patient demographics, disease specific data, supportive care utilization, and symptom burden via MPN-SAF TSS. ANOVA, chi square tests, and Wilcoxon rank sum tests methods were applied. Results: Patients:1087 patient surveys were consented. Of these, 858 had 10 or more responses. There were 338 essential thrombocytosis (ET), 188 myelofibrosis (MF), 315 polycythemia vera (PV), and 17 other. In MF: DIPSS risk categories included low (8%), Int-1 (19%), Int-2 (29%), high (12%), and unknown (32%). Supportive care:The most frequently utilized therapies were aerobic activity in 442 patients (51.5%), massage in 244 (28.4%), yoga in 220(25.6%), nutrition in 216 (25.1%), and strength training in 204 (23.7%). Symptom association: Among all respondents, aerobic activity (p=<0.001), massage (p=<0.001), yoga (p=0.02), and strength training (p=<0.001) was associated with lower symptom burden by the MPN-SAF TSS however, nutrition was not (p=0.10). In ET and PV subgroups, yoga intervention was no longer statistically significant (p=0.35, p=0.14). In the MF subgroup, no intervention was found to be significant in any risk category. Conclusions: Supportive care with aerobic activity, massage, yoga, and strength training is associated with improved symptom burden in patients with MPN. Further studies are needed to understand the benefits of such therapies. [Table: see text]
Integrative medicine modality utilization and impact on quality of life in cancer patients: A single academic cancer center experience.
Journal of Clinical Oncology | February 24, 2017 | Volume: 34 | Issue: 3_suppl | Pages: 169-169
169 Background: The majority of patients with cancer incorporate integrative medicine strategies into their cancer experience however; patient reported preferences and impact on quality of life is limited. We present cancer patient utilization for specific integrative medicine modalities within the Mayo Clinic Arizona Comprehensive Cancer center and describe the patient perceived impact on quality of life. Methods: Patients and family members attending the 2015 Living with Cancer Symposium at Mayo Clinic Arizona completed a survey indicating whether specific integrative medicine modalities were utilized during cancer treatment and whether utilization had an impact on the patients perceived quality of life. Patient diagnoses and stage were collected. A total of 119 patient surveys were completed and analyzed. Results: The patient diagnoses included hematologic malignancies (27%), breast (25%), prostate (18%), and other (30%). Disease stage was nearly evenly distributed with stage I (21%), stage II (20%), stage III (16%), stage IV (15%), and unknown (28%). The most commonly utilized integrative modalities included nutrition (54%), natural product supplementation (34%), massage (33%), exercise (31%) including yoga (23%) and tai chi (1%), breathing and meditation interventions (26-28%), support groups (23%), and pet therapy (17%). The majority of patients (64%) reported integrative intervention utilization led to an enhanced quality of life during cancer therapy. Conclusions: At a single academic cancer center, in a cancer type and stage diverse population, the majority of patients (64%) reported improved quality of life during cancer therapy with integrative medicine intervention utilization. Nutrition, natural product supplementation, massage, exercise, and meditative modalities were most commonly utilized. Interestingly, a large proportion of patients analyzed in this questionnaire-based study were afflicted with hematologic disease, a population underrepresented in the current integrative medicine intervention research. More studies exploring the feasibility and impact of integrative therapies in the hematologic patient population are needed.
Physical Activity as a Nonpharmacological Symptom Management Approach in Myeloproliferative Neoplasms: Recommendations for Future Research
Integrative Cancer Therapies | July 25, 2016 | Volume: 16 | Issue: 4 | Pages: 439-450
Purpose: Essential thrombocythemia, polycythemia vera, and myelofibrosis are rare chronic hematological malignancies known as myeloproliferative neoplasms (MPNs) and are characterized by deregulated myeloid lineage cell production, splenomegaly, and heterogeneous symptom profiles. MPN patients suffer from a significant symptom burden (eg, fatigue, depressive symptoms, early satiety) and an impaired overall quality of life (QoL). Current treatments typically include pharmacological approaches, which may come with additional side effects and may be limited by treatment-associated toxicities (ie, cytopenias). Nonpharmacological approaches such as physical activity may be beneficial for reducing symptom burden and improving QoL. To date, no studies have examined physical activity as a nonpharmacological approach in MPN patients despite preliminary evidence supporting its benefit in other hematological cancers. The purpose of this article is to (1) review the literature related to physical activity and specific hematological cancer subtypes and to (2) make suggestions for future research involving physical activity in MPN patients as a symptom management strategy. Methods: A brief review of studies examining physical activity in leukemias, lymphomas, and myelomas (excluding stem-cell transplant patients) was conducted. Results: There is preliminary evidence to suggest that physical activity may be an effective approach to improve patient-reported outcomes (fatigue, depression, anxiety, sleep), physical fitness (cardiovascular fitness, balance, body composition), and overall QoL in other hematological cancers. Conclusions: Based on encouraging findings in other hematological cancers, future research should examine the feasibility and effectiveness of physical activity in MPN patients.