The free light assay has been reported to be valuable in monitoring patients with non-secretory multiple myeloma (MM). Furthermore, because of its short half-life, it may be useful even in patients who produce intact M-proteins. Recently, FLC has also been included in a revised response criteria for MM (BGM Durie et al International uniform response criteria for multiple myeloma. Leukemia, 7/20/06, online, 1–7,2006). We decided to study the applicability of the measurement of free light chains (FLC) in patients who were treated on clinical trials at our center with novel agents such as bortezomib and lenalidomide. We followed 21 patients with non- or hyposecretory MM with FLC measurements. These patients did not have measurable intact M-proteins and had only small amount of urine total protein (UTP) or Bence-Jones protein (BJP) present (< 0.3 mg/24hours). In 7 patients on bortezomib trials and 6 patients on lenalidomide trials, the involved FLC decreased by > 50% without the ability to detect any change in the UTP or BJP. The disease response seen was confirmed by bone marrow exams when available. Conversely, in 3 patients on each of the 2 agents, there was progression (> 25% increase) in the involved FLC without measurable increase in the small amount of UTP or BJP present, confirmed by either bone marrow or skeletal progression. Thus, in these patients, the FLC provided the only convenient means of monitoring. In 14 and 12 patients on bortezomib and lenalidomide respectively who had measurable UTP and BJP or serum M-proteins, there was a > 50% decrease in the FLC upto 8 weeks before any significant changes were seen in the urine protein measures or in serum M-proteins. Furthermore, the decrease continued after the UTP and BJP had reached a low possibly threshold level. In fact, 1 complete response on bortezomib was seen, confirmed by bone marrow studies, even with residual UTP (possibly due to bisphosphonate effect). Conversely, in 11 and 10 patients on bortezomib and lenalidomide respectively with measurable UTP and BJP or serum M, the increase in the involved FLC preceded progression in the parameters by upto 6 weeks. Thus, in these patients, the FLC provided an early warning system for their response or lack thereof. With respect to the criteria included in the reference cited above, the difference between the FLC was less meaningful in those patients with renal insufficiency, since both are significantly elevated in this state. The ratio however was the least meaningful since it was either 0 or infinite for a long time period depending upon which FLC was involved. Thus, FLC measurements are useful for monitoring patients who might not otherwise be eligible or benefit from clinical trials of novel agents. It can also serve as a early harbinger of response or progression. However, the limitations of the assay with respect to ratios and differences need to noted.
Disclosures: Celgene, Millenium.; Celgene, Millenium.; Celgene, Millenium.
