Content development for the Functional Assessment of Cancer Therapy-Multiple Myeloma (FACT-MM): use of qualitative and quantitative methods for scale construction.

CONTEXT: Multiple myeloma (MM) is a common hematologic malignancy and is associated with symptom burden and impairments in health-related quality of life (HRQL). OBJECTIVES: To develop a disease-specific, patient-reported outcome (PRO) measure for the assessment of HRQL among patients with MM as part of the Functional Assessment of Cancer Therapy (FACT) measurement system. METHODS: HRQL concerns and symptoms associated with MM were tabulated based on a literature review, and 52 candidate PRO items were identified. Expert clinicians (n=13) rated 52 items on relevance to HRQL for MM patients (0-3 scale). Experts added 11 items for comprehensive PRO assessment in MM. A list of 63 candidate items was rated (0-3 scale) by 13 MM patients enrolled through the International Myeloma Foundation website. Qualitative data and quantitative item ratings were reviewed to select FACT-MM scale items. RESULTS: Expert clinicians provided the highest HRQL relevance ratings for bone pain, bodily pain, difficulty walking (2.9), tiring easily (2.6), feeling discouraged (2.5), interference with activities and difficulty with self-care as a result of bone pain (2.5), and fatigue (2.5). Mean age of patients was 57 years; Eastern Cooperative Oncology Group performance status was 0 (38%), 1 (31%), or 2 (31%). Quantitative ratings by patients identified sexual function (1.3), uncertainty about health (1.2), fatigue (1.0), weight gain (1.0), and emotional concerns, such as worry about new symptoms and difficulty planning for the future (1.0) as most relevant to HRQL. CONCLUSION: The 14-item FACT-MM PRO measure was developed based on expert clinician and patient data, ensuring relevance to HRQL for MM patients.

A comparison of lenalidomide/dexamethasone versus cyclophosphamide/lenalidomide/dexamethasone versus cyclophosphamide/bortezomib/dexamethasone in newly diagnosed multiple myeloma.

Novel agents are considered standard components of induction therapy for newly diagnosed patients with multiple myeloma. We retrospectively compared the results of three consecutive phase 2 clinical trials; RD (lenalidomide/dexamethasone, n=34), CRD (cyclophosphamide/lenalidomide/dexamethasone, n=53) and CyBorD (cyclophosphamide/bortezomib/dexamethasone, n=63) (N=150). Response rates after four cycles of treatment were: ≥near complete response (nCR), 12% vs. 2% vs. 41%, P<0·0001 and very good partial response or better, 35% vs. 30% vs. 65%, P=0·0003, respectively. With all cycles of therapy considered, ≥nCR was 35%, 15% and 41%, P=0·006. However, there is no evidence that one regimen produced superior progression-free survival (PFS) (median: 3·2 vs. 2·3 vs. 2·7years, P=0·11) or overall survival (3-year: 88% vs. 79% vs. 88%, P=0·23). Transplantation did not impact PFS (median: 2·7 vs. 2·3 years, P=0·41) but was associated with improved OS (3-year: 93% vs. 75%, P≤0·001). High genetic risk patients (n=40) had earlier relapse despite lenalidomide or bortezomib (median: 2·1 vs. 2·7years, P=0·45). Grade 3/4 toxicities were least with CyBorD while CRD had most toxicity. In conclusion, CyBorD demonstrated superior responses and less frequent serious toxicity but more neuropathy when compared to RD and CRD. Importantly, 80% of patients treated with modern therapeutic approaches are alive at 4years.

A novel report of cig-FISH and cytogenetics in POEMS syndrome.

POEMS syndrome is a plasma cell proliferative disorder whose pathogenesis is poorly understood. We provide the first report of cytoplasmic immunoglobulin/FISH testing (cIg-FISH) in POEMS syndrome using established myeloma markers. We reviewed all 37 POEMS cases seen at our institution in which cIg-FISH testing had been obtained. Monosomy 13 was seen in 14 of the 37 (38%) cIg-FISH samples. One patient had trisomy 3 and 7. Three patients had IgH translocation t(11;14)(q13;q32). No abnormalities were seen at 17p13(p53). The monosomy 13 is in line with other plasma cell disorders while the low prevalence of hyperdiploidy and abnormalities at 14q32 is unique.

A phase II trial of imatinib in patients with refractory/relapsed myeloma.

Although imatinib was designed to specifically inhibit the bcr-abl gene product, it inhibits other receptor tyrosine kinases including c-kit. As pre-clinical data, 126 patients with plasma cell disorders and 19 controls were evaluated for c-kit expression. Patients were eligible for the treatment trial if they had relapsed/refractory myeloma. The primary end-point of the study was response. Of the 145 studied before the trial, c-kit expression was present on the bone marrow plasma cells of control (11%), AL amyloid (53%), MGUS (47%), SMM (67%) and MM (42%) patients. Twenty-three MM patients were enrolled on the therapeutic trial (imatinib 400 mg daily) and 52% had positive c-kit staining. There were no responses. The median duration of treatment was 48 days (range: 12-349). Patients ended treatment due to progressive disease (18 patients), death (3) and other (2). The data suggest that imatinib is not an active agent in patients with relapsed or refractory multiple myeloma.