Validation of the Serial Use of the Myelofibrosis Symptom Assessment Form (MF-SAF) for Measuring Symptomatic Improvement: Performance in 86 Myelofibrosis Patients On INCB018424 Clinical Trial.

Abstract 3917 Poster Board III-853 Background Patients with Myelofibrosis (MF) suffer from significant fatigue, constitutional symptoms and splenomegaly (Mesa et. al. Cancer 2007) not improved by current therapy. The MF-SAF is a 19 item self administered instrument specific to MF associated symptoms previously validated for use at a single time point (Mesa et. al. Leukemia Research 2009). We sought to assess the performance characteristics of the MF-SAF when administered sequentially in the context of a prospective clinical trial. Methods Sequential MF patients enrolled in the prospective, uncontrolled Phase II, trial were given a 15 item modified MF-SAF to complete at enrollment, and after 15 days, 1 month, 2 months, 3 months and every 3 months thereafter. The MF-SAF was scored as previously published on a 0 (absent) to 10 (maximal) scale. Cross validation of serial change in MF-SAF scores was undertaken by comparison to objective measurements made as part of the therapeutic drug trial. Results Patients Eighty six MF patients were enrolled and had 2 or more MF-SAF instruments completed to allow for sequential analysis. Patients were of a median age (65 years), gender distribution (35 % females), and disease subtype (53 % PMF) typical for a clinical trial in MF. Baseline MF-SAF Responses: Baseline assessment of the most frequent MF abnormalities reported by patients completing the MF-SAF (see [Table 1][1]) confirmed the wide prevalence of MF associated symptoms, and their significant severity. General fatigue was the most frequent symptom cited (91%), while cough was the least frequently observed symptom (44%). 95% of patients had at least 2 symptoms present on the MF-SAF. Serial MF-SAF Changes in Response to Therapy Therapy with INCB018424 resulted in a significant and rapid reduction in MF associated symptoms with 46% to 85% of patients experiencing improvement in a given symptom. The greatest improvements in MFSAF score improvements were reported by patients experiencing abdominal discomfort, night sweats, pruritus and fever (see [Table 1][1]), and corresponded to significant improvements in the individual MF symptom scales as well as the patient's overall assessment of quality of life (QOL). Correlation of MF-SAF to Objective Changes during INCB018424 Therapy Objective measurements obtained on the INCB018424 trial included MRI measurements of splenic reduction, the six minute walk test (6MWT) for inactivity, and serial weights. Reduction in spleen size (by ≥ 35% by volume or ≥ 50% by palpable length) corresponded to improvement in MF-SAF scores of abdominal discomfort and fatigue (50% of patients, median score decrease of -1.2, and -1.8, respectively). Improvement in the 6MWT by > 50 meters was associated with a 2-fold greater improvement in inactivity score on the MF-SAF compared to subjects who improved 6MWT performance by <50 meters. Finally, improvements in weight loss and fever were corroborated by objective measurements made at physician visits on the trial. Conclusions The MF-SAF is a brief, easily self administered, MF specific instrument which was successfully administered sequentially in the conduct of a large Phase II clinical trial. The significant symptomatic improvements reported by patients in the open label trial of INCB018424 corresponded to both improvements in symptom specific scores on the MF-SAF and objective measurements. Further validation of the MF-SAF will be possible by inclusion in upcoming randomized placebo controlled trials in MF patients. Parallel trials performed in MF patients should consider use of this instrument to allow for comparisons. | | General Fatigue* | Abdom Pain/ Discomfort | Night Sweats | Pruritus | Bone/Muscle Pain | Fever | Cough | Appetite (wt gain or loss) | Ability to move/walk | QOL | |:--------------------------------------------- | ---------------- | ---------------------- | ------------ | -------- | ---------------- | ----- | ----- | -------------------------- | -------------------- | ---- | | N = | 86 | 86 | 85 | 86 | 84 | 86 | 86 | 86 | 86 | 86 | | % with baseline score of > 1 | 91% | 76% | 54% | 45% | 65% | 54% | 44% | 74% | 83% | 91% | | Median Baseline Score | 4.0 | 3.0 | 4.0 | 2.0 | 3.0 | 2.0 | 2.0 | 2.5 | 3.0 | 4.0 | | % Improved | 53% | 66% | 83% | 85% | 46% | 77% | 76% | 61% | 54% | 50% | | Median Score at 6 Months | 2.0 | 1.0 | | | 2.0 | | | 1.0 | 2.0 | 2.0 | | Median Score change from baseline at 6 months | -1.0 | -2.0 | -2.0 | -1.0 | | -2.0 | -1.0 | -1.0 | -1.0 | -1.0 | Table 1 Baseline and Serial change in Myelofibrosis Symptoms in 86 Patients Taking INCB018424 Disclosures: Levy: Incyte Corporation: Employment, Equity Ownership. Vaddi: Incyte Corporation: Employment, Equity Ownership. Erickson-Viitanen: Incyte Corporation: Employment, Equity Ownership. Verstovsek: Incyte: Research Funding. [1]: #T1