Serum Free Light Chain Measurement Has Prognostic Value in All Stages of Myeloma

A normalized serum free light chain (sFLC) ratio in multiple myeloma treatment following a complete response has been tied to better survival. For those patients who don’t achieve complete response an sFLC measurement may still be a powerful prognostic tool for disease monitoring, according to researchers at the Mayo Clinic in Rochester, Minnesota, who report their findings in the journal Leukemia.

“What we have been able to show is that a normal sFLC ratio in a patient who achieved partial response after treatment of his or her myeloma is associated with an improved survival outcome, suggesting that the sFLC data may be providing information regarding the disease biology rather than being a simple quantitative estimate of tumor burden,” corresponding author Shaji Kumar, MD, professor of medicine at the Mayo Clinic, told ASH Clinical News.

In the retrospective study led by Muhamad Moustafa MD, also of the Mayo Clinic, the investigators analyzed medical records of 449 newly diagnosed patients (median age, 65 years) with measurable disease (serum M-spike ≥1 g/dl at the time of diagnosis). Researchers then analyzed patients’ serum electrophoresis results and sFLC values corresponding with the date of best response.

The most common first-line therapy for the cohort was lenalidomide with or without dexamethasone (212 patients [47%]). Thirty-four patients (8%) also received cyclophosphamide or melphalan in combination with this treatment. A bortezomib-based regimen was used in 60 patients (13%); 15 patients (3%) received bortezomib-lenalidomide-dexamethasone; and four patients (1%) were treated with bortezomib-thalidomide-dexamethasone. Of the remaining patients, 45 (10%) had a thalidomide-based regimen, while 79 (18%) had conventional therapies.

The authors reported that 363 patients (81%) achieved a partial response or better, including 144 patients (32%) with a “very good” partial remission and 219 patients (49%) with a partial response.

“The median time to the best first response for the whole cohort was 6.9 months (range, 0.3-83 months),” they wrote. “The median progression-free survival from time of diagnosis was 21 months (95% CI 19-24) for those achieving a partial response or better, compared with seven months (95% CI 5-12) for the remainder (p<0.001).”

In terms of sFLC ratios at the time of best first response:

  • 153 patients (34%) had a normal sFLC ratio
  • 296 patients (66%) had an abnormal sFLC ratio

sFLC ratio normalization was associated with improved progression-free survival in each of three response groups (stable disease, partial response, or very good partial response); however, when considering overall survival, only partial response patients who had a normal sFLC ratio had a better outcome (TABLE).

Due to the diagnostic insight sFLC ratio measurements demonstrated in the study, Dr. Kumar predicts that this measurement will start to be used in additional settings in multiple myeloma therapy.

“Currently, the response criteria in myeloma utilizes only sFLC measurements for confirmation of stringent complete response and in patients with light chain–only multiple myeloma,” he noted. “We believe that the current study should raise the question as to whether we should be measuring sFLC in all stages of response. Until we adopt such a change to the response criteria, though, we recommend using it only in the situations described above.”

In current practice, sFLC testing should be done at baseline and at the time complete response is obtained in all patients, Dr. Kumar emphasized.

However, in patients with light chain–only myeloma, the measurements would be done at baseline and after every one to two cycles of treatment for response assessment, he explained. “Intermittent assessment of sFLC in patients who are in a plateau phase after responding to therapy will allow for prompt detection of light chain escape – a phenomenon where myeloma cells stop making an intact immunoglobulin and only secrete a light chain,” he said.

The study limitations associated with a retrospective study design, including the potential for ascertainment bias, and there was also a lack of predefined schedules for response assessments. Enrolled patients were seen at a referral center, so approximately 20 percent did not have baseline sFLC measurements. Finally, the types of anti-myeloma therapies used, and the duration of treatments, varied widely among the patient cohort.


Reference

Moustafa M, Rajkumar S, Dispenzieri A, et al. Utility of serum free light chain measurements in multiple myeloma patients not achieving complete response to therapy. Leukemia. 2015 May 12. [Epub ahead of print]


TABLE. Effect of sFLC Ratio Normalization on Survival Outcomes According to IMWG Response Categories
Stable Disease Partial Response Very Good Partial Response
Normal sFLC ratio (n=7) Abnormal sFLC ratio (n=70) p Value Normal sFLC ratio (n=62) Abnormal sFLC ratio (n=157) p Value Normal sFLC ratio (n=85) Abnormal sFLC ratio (n=60) p Value
Progression-free survival, months, median (95% CI) 27 (14-36) 6 (4-10) 0.008 26 (20-36) 17 (13-20) 0.0005 29 (23-34) 21 (18-26) 0.02
Overall survival, months, median (95% CI) 68 (49-68) 41 (30-57) Not significant NR (65 – NR) 61 (50 – NR) 0.004 91 (67-107) 73 (59 – NR) Not significant
*NR = not reached

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