Abstract
BACKGROUND: MM is the second most common hematalogical malignancy in the U.S. The expansion of myeloma cells in bone, which is characteristic of MM, results in increased osteoclast activity that cause osteolytic lesions, which can lead to spinal cord compression, pathologic fracture, surgery or radiation therapy to bone, and bone pain. Denosumab is a fully human monoclonal antibody that can inhibit bone resorption by reducing the number and activity of osteoclasts by inhibiting RANK ligand, a key mediator of osteoclast activity. The objective of this analysis was to evaluate the pain and HRQoL in patients with MM being treated with denosumab.
METHODS: 96 patients with either ≥2 prior treatment regimens and relapsed following a response to any conventional MM therapy (relapsed) or response to the most recent MM therapy and stable M-protein for ≥3 months (PP) were enrolled in a phase 2, multicenter, open-label, single-arm study of denosumab. Patients received 120mg denosumab SC on days 1, 8, 15, and 29 then every 28 days thereafter until disease progression or discontinuation. The Brief Pain Inventory-Short Form (BPI) and Functional Assessment of Cancer Therapy-General (FACT) were assessed at baseline (BL) and prior to treatment on day 1 of each 28-day cycle. BPI “pain at worst in the past 24 hours” scores were categorized as no pain (BPI 0), mild pain (BPI 1–4), moderate pain (BPI 5–6) or severe pain (BPI 7–10). BL and month 3 (relapsed) and month 5 (PP) pain and HRQoL data were analyzed. Longitudinal data regarding pain and HRQoL data were reported at BL and the latest assessment timepoint where <30% of patients had dropped out.
RESULTS: 45 patients with relapsed MM (Table 1) and 37 patients with PP MM (Table 2) had BL and ≥1 post-BL assessment. 30% or more patients dropped out after month 3 of treatment in relapsed patients and after month 5 in PP patients. In relapsed patients, 12 (27%), 21 (47%), 8 (18%), and 4 (9%) patients reported no pain, mild pain, moderate pain and severe pain at BL, respectively. In PP patients, 15 (41%), 13 (35%), 5 (14%), and 4 (11%) patients reported no pain, mild pain, moderate pain and severe pain at BL, respectively. 68% and 89% of relapsed and PP patients, respectively, demonstrated improvement or no categorical change in pain. At BL, mean (sd) FACT total scores (0–108, higher score indicating better HRQoL) for relapsed and PP patients were 77.4 (15.3) and 82.5 (11.2), respectively. FACT total scores remained relatively constant in relapsed and PP patients, 77.9 (19.4) and 83.6 (13.3), respectively. In addition, mean change from baseline in FACT domain scores varied between 1.2 to 0.2 in relapsed patients and between 0.3 to 1.1 in PP patients.
CONCLUSION: The majority of patients with relapsed and PP MM demonstrated maintenance or improvement in pain and maintenance of HRQoL during treatment with denosumab. These results suggest denosumab may be associated with stabilization of pain and maintenance of HRQoL in patients with MM. Randomized trials are needed to further understand the impact of denosumab on pain and HRQoL in patients with MM.
Table 1. “Pain at Worst in the past 24 hours” Category Shift between BL and month 3 in relapsed patients (n=45).
Follow-up Pain Category No Pain Mild Moderate Severe TOTAL BL Pain Category No Pain 7 2 2 1 12 Mild 4 10 4 3 21 Moderate 2 3 1 2 8 Severe 0 0 2 2 4 TOTAL 13 15 9 8 45
Table 2. “Pain at Worst in the past 24 hours” Category Shift between BL and month 5 in PP patients (n=37).
Follow-up Pain Category No Pain Mild Moderate Severe TOTAL BL Pain Category No Pain 13 2 0 0 15 Mild 4 7 1 1 13 Moderate 1 2 1 1 5 Severe 0 0 2 2 4 TOTAL 18 11 4 4 37
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