Validation Of The Functional Assessment Of Cancer Therapy - Lymphoma (Fact-Lym) In Patients With Relapsed/Refractory Mantle Cell Lymphoma.

Abstract BACKGROUND: The FACT-Lym was developed to assess health-related quality of life (HRQL) in patients with non-Hodgkin’s lymphoma (NHL). Cella and colleagues developed the instrument in a general NHL population, including patients with either aggressive or indolent disease (Cella et al, Proc ASH 2005). The current research explores the validity of the FACT-Lym in patients with relapsed/refractory mantle cell lymphoma (MCL) and estimates minimally important differences (MIDs), which can be defined as the smallest change in a patient-reported outcome (PRO) measure that may be perceived as beneficial or result in change in treatment. Data were collected as part of a phase II, single-arm, open-label study of enzastaurin in relapsed/refractory MCL patients (Morschhauser et al, Ann Oncol 2008). METHODS: The FACT-Lym (version 4) was administered prior to the start of therapy, at 2-month intervals while on therapy for up to 6 months, and approximately 30 days after discontinuation. The 30-day discontinuation assessment was commonly associated with disease progression. Descriptive statistics were used to report FACT-Lym scores, with emphasis placed on the lymphoma-specific subscale, the total FACT-Lym, and the Trial Outcome Index (TOI; physical and functional well-being plus lymphoma-specific subscale). Criterion validity was assessed by grouping patients by International Prognostic Index (IPI) (assessed at study entry) and by baseline Eastern Cooperative Oncology Group performance status (PS). Patients were grouped according to changes in: PS (improved/stable or worse) and clinical status from baseline to 30-day discontinuation, to assess the FACT-Lym’s responsiveness to change (i.e., ability of an instrument to detect change in clinical status). Analyses included t-tests and one-way analysis of variance (ANOVA). Distribution- and anchor-based methods were used to estimate MIDs. Distribution-based methods included estimates using the standard error of measurement (SEM) and 1/3 or 1/2 standard deviation (SD) approach. Anchors were PS and disease progression. RESULTS: FACT-Lym data were available for 59 of the 60 enrolled patients at baseline and for 40 patients at discontinuation. One patient who did not meet protocol qualifications was excluded from these analyses. The most common reason for missing data was the site failing to administer the instrument. Median age was 66 years, 70% were male, 88% had a baseline PS of 0 or 1, and 52% had an IPI score ≤2. The table below summarizes the baseline and 30-day discontinuation FACT-Lym scores and makes comparisons across IPI and PS scores at baseline. Mean lymphoma subscale, TOI, and total scores were significantly (p<0.05) different between baseline and the 30-day assessment; the differences were −4.8, −10.6, and −11.7 respectively. There was significant difference in the change of the scores from baseline to discontinuation between those patients with improved/stable PS (n=20) and those patients with worsened PS (n=16). For those patients with worsened PS, scores were significantly worse. The estimated MID ranges across the varying methodologies were: lymphoma subscale 2.9–5.4, TOI 5.5–11, and total FACT-Lym 6.5–11.2. CONCLUSIONS: We demonstrated with this retrospective study that the FACT-Lym is valid instrument to assess HRQL in patients with relapsed/refractory MCL. With the FACT-Lym, we were able to differentiate patients based on PS and to measure changes in HRQL associated with worsening health status. IPI was shown to not be a differentiating factor for the FACT-Lym. Despite the limited sample size, these findings are consistent with results from the initial validation work and support the use of the FACT-Lym in patients with MCL. These results can be used to inform future trial designs for relapsed/refractory aggressive lymphoma. FACT-Lym Scores and Comparisons across PS and IPI Groups Lymphoma subscale (0–60) TOI (0–116) Total FACT-Lym (0–168) n Mean ± SD p-value Mean ± SD p-value Mean ± SD p-value Baseline All patients 58 46.3 ± 8.8 - 85.1 ± 16.7 - 123.9 ± 22.3 - PS 0.003 <0.001 0.022 0 26 50.2 ± 6.8 93.0 ± 13.2 131.2 ± 19.8 1 25 44.0 ± 9.2 81.5 ± 15.8 120.6 ± 21.7 2 7 39.9 ± 7.9 68.7 ± 16.4 105.6 ± 25.4 IPI 0.467 0.217 0.587 ≤2 28 47.0 ± 8.7 87.8 ± 13.9 125.2 ± 20.1 ≥3 26 45.3 ± 8.9 82.0 ± 19.5 121.8 ± 25.6 Discontinuation 39 42.8 ± 10.7 - 77.0 ± 22.3 - 115.0 ± 27.6 -