Xiaolei Zhou

Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study

PURPOSEnTwenty percent of patients with follicular lymphoma (FL) experience progression of disease (POD) within 2 years of initial chemoimmunotherapy. We analyzed data from the National LymphoCare Study to identify whether prognostic FL factors are associated with early POD and whether patients with early POD are at high risk for death.nnnPATIENTS AND METHODSnIn total, 588 patients with stage 2 to 4 FL received first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Two groups were defined: patients with early POD 2 years or less after diagnosis and those without POD within 2 years, the reference group. An independent validation set, 147 patients with FL who received first-line R-CHOP, was analyzed for reproducibility.nnnRESULTSnOf 588 patients, 19% (n = 110) had early POD, 71% (n = 420) were in the reference group, 8% (n = 46) were lost to follow-up, and 2% (n = 12) died without POD less than 2 years after diagnosis. Five-year overall survival was lower in the early-POD group than in the reference group (50% v 90%). This trend was maintained after we adjusted for FL International Prognostic Index (hazard ratio, 6.44; 95% CI, 4.33 to 9.58). Results were similar for the validation set (FL International Prognostic Index-adjusted hazard ratio, 19.8).nnnCONCLUSIONnIn patients with FL who received first-line R-CHOP, POD within 2 years after diagnosis was associated with poor outcomes and should be further validated as a standard end point of chemoimmunotherapy trials of untreated FL. This high-risk FL population warrants further study in directed prospective clinical trials.

Health-related quality of life and symptoms in patients with myelofibrosis treated with ruxolitinib versus best available therapy.

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.

Prevalence, incidence, and treatments of Dupuytren’s disease in the United States: results from a population-based study

BackgroundThis large population-based study was conducted to estimate the prevalence of Dupuytren’s disease in US adults and describe associated treatment patterns.MethodsA total of 23,103 individuals from an Internet-based research panel representative of the US population completed a brief online survey designed to identify individuals with symptoms, diagnoses, and/or treatment experience indicative of Dupuytren’s disease (mean age = 50xa0years).ResultsThe prevalence of Dupuytren’s disease defined as a self-reported physician diagnosis and/or surgical treatment was estimated as 1% (95% CI = 0.8–1.2), but the estimated prevalence is much higher (7.3%) when including self-reported symptoms of ropelike growth or hard bumps on the hand. The annual incidence proportion was estimated at about 3 cases per 10,000 adults. A total of 326 participants who reported relevant Dupuytren’s symptoms, treatment, and/or diagnosis completed a more in-depth survey focusing on timing of medical treatments after first symptom noticed, description of functional impairment, treatment patterns, and family history. From the second survey, most patients who reported seeking treatment for hand symptoms initially saw a primary care physician, and the mean time from noticing the first hand symptom to seeing a doctor was 23.1xa0months. At their first doctor visit for hand symptoms, only 9% of patients received a diagnosis of Dupuytren’s disease and 48% were advised to “wait and see” or received no treatment.ConclusionsResults from the current study indicate a number of unmet medical needs, so strategies to raise physician awareness of disease symptoms and effective treatment options may be helpful.

Examination of the follicular lymphoma international prognostic index (FLIPI) in the National LymphoCare study (NLCS): a prospective US patient cohort treated predominantly in community practices

BACKGROUNDnBecause follicular lymphoma (FL) patients have heterogeneous outcomes, the FL international prognostic index (FLIPI) was developed to risk-stratify patients and to predict survival. However, limited data exist regarding the role of FLIPI in the era of routine first-line rituximab (R) and R-chemotherapy regimens and in the setting of community oncology practices.nnnPATIENTS AND METHODSnWe evaluated the outcome data from the National LymphoCare Study (NLCS), a prospective, observational cohort study, which collects data on patients with FL in the United States (US) community practices.nnnRESULTSnAmong 1068 male and 1124 female patients with FLIPI data, most were treated in US community practices (79%); 35% were FLIPI good risk, 30% intermediate risk, and 35% poor risk. FLIPI risk groups were significant predictors of overall survival (OS) and progression-free survival (PFS) for patients who undergo watchful waiting (WW), and those who receive non-R-containing regimens, R-alone, and R-chemotherapy combinations.nnnCONCLUSIONSnIn the setting of contemporary practice with routine R use, stratifying patients into good, intermediate, and poor FLIPI risk groups predicts distinct outcomes in terms of OS and PFS. FLIPI remains an important prognostic index in the R era and should be used in clinical practices to support discussions about prognosis.BACKGROUNDnBecause follicular lymphoma (FL) patients have heterogeneous outcomes, the FL international prognostic index (FLIPI) was developed to risk-stratify patients and to predict survival. However, limited data exist regarding the role of FLIPI in the era of routine first-line rituximab (R) and R-chemotherapy regimens and in the setting of community oncology practices.nnnPATIENTS AND METHODSnWe evaluated the outcome data from the National LymphoCare Study (NLCS), a prospective, observational cohort study, which collects data on patients with FL in the United States (US) community practices.nnnRESULTSnAmong 1068 male and 1124 female patients with FLIPI data, most were treated in US community practices (79%); 35% were FLIPI good risk, 30% intermediate risk, and 35% poor risk. FLIPI risk groups were significant predictors of overall survival (OS) and progression-free survival (PFS) for patients who undergo watchful waiting (WW), and those who receive non-R-containing regimens, R-alone, and R-chemotherapy combinations.nnnCONCLUSIONSnIn the setting of contemporary practice with routine R use, stratifying patients into good, intermediate, and poor FLIPI risk groups predicts distinct outcomes in terms of OS and PFS. FLIPI remains an important prognostic index in the R era and should be used in clinical practices to support discussions about prognosis.

The use and effectiveness of rituximab maintenance in patients with follicular lymphoma diagnosed between 2004 and 2007 in the United States.

The authors examined the “real‐world” effectiveness of rituximab (R) maintenance therapy (R‐maintenance) compared with observation after R‐based induction therapy in patients with previously untreated follicular lymphoma (FL) in the United States.

Outcomes following watchful waiting for stage II-IV follicular lymphoma patients in the modern era

To examine the effectiveness of an initial management strategy of watchful waiting for follicular lymphoma (FL) in clinical practice, we compared outcomes for patients diagnosed 2004–2007 in the United States initially managed with watchful waiting with outcomes following initial rituximab monotherapy and chemoimmunotherapy. In total, 1754 stage II–IV patients in the National LymphoCare Study underwent watchful waiting (n = 386), rituximab monotherapy (n = 296) or rituximab plus chemotherapy (n = 1072) as initial management strategy. Female patients and those who received treatment in the Northeast or in an academic setting more commonly underwent watchful waiting versus initial chemoimmunotherapy; whereas patients with grade 3 histology, anaemia, elevated lactate dehydrogenase, extranodal involvement, B symptoms or performance status ≥1 more commonly received chemoimmunotherapy. Although time to new treatment and progression‐free survival following first‐ and second‐line therapy were improved with chemoimmunotherapy, and time to chemotherapy was improved with rituximab monotherapy, there were no differences in overall survival between watchful waiting and chemoimmunotherapy or rituximab monotherapy. With 8‐year overall survival estimates of 74%, initial management with watchful waiting in the context of sequential therapy remains a viable option for FL patients in the modern era. This trial was registered at www.clinicaltrials.gov (NCT00097565).

Disease, treatment, and outcome differences between men and women with follicular lymphoma in the United States

We aimed to comprehensively study sex differences in disease and patients characteristics, treatment and outcomes in patients with follicular lymphoma (FL) in the United States (USA) utilizing the National LymphoCare Study registry (2004–2014). Among evaluable males (nu2009=u20091277) and females (nu2009=u20091375) with FL, females less commonly received anthracyclines and were more likely to receive rituximab monotherapy. Overall response rates were comparable between sex groups. With a median follow‐up of 8.1 years, male sex emerged as an adverse factor for PFS (HR, 0.84, 95% CI, 0.72–0.97). Lymphoma‐related mortality (HR, 0.46; 0.23–0.93) and overall survival (HR, 0.63; 0.41–0.97) favored females aged ≤60 years. There are subtle differences in outcomes between male and female FL patients diagnosed and treated in the contemporary era. These data represent the largest prospective analysis of FL patients in the USA based on sex and can aid design of clinical trials for this disease. Am. J. Hematol. 91:770–775, 2016.

Disease characteristics, treatment patterns, prognosis, outcomes and lymphoma‐related mortality in elderly follicular lymphoma in the United States

Data from the National LymphoCare Study (a prospective, multicentre registry that enrolled follicular lymphoma (FL) patients from 2004 to 2007) were used to determine disease characteristics, treatment patterns, outcomes and prognosis for elderly FL (eFL) patients. Of 2650 FL patients, 209 (8%) were aged >80 years; these eFL patients more commonly had grade 3 disease, less frequently received chemoimmunotherapy and anthracyclines, and had lower response rates when compared to younger patients. With a median follow‐up of 6.9 years, 5‐year overall survival (OS) for eFL patients was 59%; 38% of deaths were lymphoma‐related. No treatment produced superior OS among eFL patients. In multivariate Cox models, anaemia, B‐symptoms and male sex predicted worse OS (P < 0·01); a prognostic index of these factors (0, 1 or ≥2 present) predicted OS [hazard ratio (95% CI): ≥2 vs. 0, 4·72 (2·38–9·33); 1 vs. 0, 2·63 (1·39–4·98)], with a higher concordance index (0·63) versus the Follicular Lymphoma International Prognostic Index (0·55). The index was validated in an independent cohort. In the largest prospective US‐based eFL cohort, no optimal therapy was identified and nearly 40% of deaths were lymphoma‐related, representing baseline outcomes in the modern era.

Disease characteristics, treatment patterns, and outcomes of follicular lymphoma in patients 40 years of age and younger: an analysis from the National Lymphocare Study

BACKGROUNDnFollicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma, with median age at diagnosis in the seventh decade. FL in young adults (YAs), defined as diagnosis at ≤40 years, is uncommon. No standard approaches exist guiding the treatment of YA FL, and little is known about their disease characteristics and outcomes. To gain further insights into YA FL, we analyzed the National LymphoCare Study (NLCS) to describe characteristics, initial treatments, and outcomes in this population versus patients aged >40 years.nnnPATIENTS AND METHODSnUsing the NLCS database, we stratified FL patients by age: 18-40 (YA), 41-60, 61-70, 71-80, and >80 years. Survival probability was estimated using Kaplan-Meier methodology. We examined associations between age and survival using hazard ratios and 95% confidence intervals (CIs) from multivariable Cox models.nnnRESULTSnOf 2652 eligible FL patients in the NLCS, 164 (6%) were YAs. Of YA patients, 69% had advanced disease, 80% had low-grade histology, and 50% had good-risk disease according to the Follicular Lymphoma International Prognostic Index (FLIPI). Nineteen percent underwent observation, 12% received rituximab monotherapy, and 46% received chemoimmunotherapy [in 59% of these: R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone)]. With a median follow-up of 8 years, overall survival (OS) at 2, 5, and 8 years was 98% (95% CI 93-99), 94% (95% CI 89-97), and 90% (95% CI 83-94), respectively. Median progression-free survival (PFS) was 7.3 years (95% CI 5.6-not reached).nnnCONCLUSIONSnIn one of the largest cohorts of YA FL patients treated in the rituximab era, disease characteristics and outcomes were similar to patients aged 41-60 years, with favorable OS and PFS in YAs. Longer-term outcomes and YA-specific survivorship concerns should be considered when defining management. These data may not support the need for more aggressive therapies in YA FL.nnnCLINICAL TRIAL NUMBERnRoche/Genentech ML01377 (U2963n).

Assessing Methotrexate Adherence in Rheumatoid Arthritis: A Cross-Sectional Survey

IntroductionLimited data are available to explain nonadherence to methotrexate (MTX) therapy in patients with rheumatoid arthritis (RA). Better understanding of patterns of MTX use and reasons for nonadherence may help identify patients who would benefit from alternative RA treatments and potentially aid in developing strategies to increase overall adherence. The purpose of this study was to assess patients’ self-reported adherence to MTX and to identify reasons for nonadherence.MethodsPatient panel members in the US self-reporting a diagnosis of RA of ≥3xa0months’ and current MTX use of ≥4xa0weeks’ duration, with or without concomitant use of another RA prescription medication, participated in this cross-sectional, web-based survey.ResultsThe sample population (251 MTX monotherapy, 250 MTX combination therapy) was predominantly female, white, non-Hispanic, and educated; 48% were 18–44xa0years-old, 47% had medical comorbidities, 66% were first diagnosed with RA ≤5xa0years earlier, 51% reported MTX use of <1xa0year, and 83% reported oral MTX use. Forty-two percent reported not taking MTX exactly as prescribed. Reasons for nonadherence included forgetting to take it (33%), not needing it when feeling well (24%), and concern about long-term safety (24%). Among nonadherent patients, 53% took smaller doses, 52% skipped doses, and 6% reported other nonprescribed ways of taking MTX. Younger age, male sex, and shorter duration of MTX use were associated with poorer self-reported adherence. Compared with monotherapy patients, combination therapy patients, particularly those taking ≥2 other RA prescriptions, were less likely to report high adherence.ConclusionNearly half the sample reported poor MTX adherence because they forgot to take it, thought it was not needed when they felt well, or had long-term safety concerns. Patients taking ≥2 other RA prescription medications were less likely to report good adherence. Reducing treatment burden without sacrificing efficacy may be a strategy worth evaluating.