Impact of Baseline Free Light Chain Ratio (rFLC) On Clinical Outcomes and Change in rFLC During Treatment in Patients with Relapsed/Refractory Multiple Myeloma Treated with Pegylated Liposomal Doxorubicin Plus Bortezomib or Bortezomib Alone.
Authors: Magarotto Valeria , Londhe Anil , Lantz Keith C. , Lowery Colin , Sonneveld Pieter , Bladé Joan , Harousseau Jean-Luc , Orlowski Robert Z. 
Published: October 2019

Abstract 4778

Background

The serum immunoglobulin-free light chain (sFLC) assay measures levels of free κ and » immunoglobulin light chains. In multiple myeloma (MM), similar to other plasma cell dyscrasias, a secretory dysfunction causes an abnormal sFLC (κ/») ratio (rFLC). The rFLC (normal range: 0.26-1.65) is a requirement for documenting stringent complete remission (sCR) and can be a prognostic indicator in newly diagnosed multiple myeloma (Dispenzieri et al. for the International Myeloma Working Group, Leukemia, 2009). As part of a randomized controlled study in MM (Orlowski et al., JCO 2007), we previously have shown that the normalization of rFLC after the first 2 cycles of pegylated liposomal doxorubicin (PLD) + bortezomib (B) or B alone is associated with a prolonged time to progression (TTP) and higher response rate (RR) among patients with relapsed/refractory MM (Orlowski et al., Blood 2007, abstract #2735).

In this analysis, we examined how baseline ratios of sFLC impacted clinical outcomes (TTP and RR), and if sFLC ratios changed over the course of treatment in patients receiving PLD + B or B alone.

Methods

Patients with ≥1 prior therapy were randomized to receive PLD at 30 mg/m2 on day 4 with B at 1.3 mg/m2 on Days 1, 4, 8, and 11, or B alone on this same dose and schedule, for up to eight 21-day cycles, or at least 2 cycles beyond complete response (CR) or optimal response, unless disease progression or unacceptable toxicities occurred. Serial serum κ/» measurements were made prior to the start of therapy and at the end of each cycle throughout the entire study using an immunoassay (Freelite, The Binding Sites, Birmingham, UK).

Results

Sera from 491 patients were available for these analyses: 31 patients (6.3%) had a normal baseline rFLC, while 460 patients (93.6%) had an abnormal baseline rFLC (<0.26 or >1.65). Among patients with a normal baseline rFLC, 14 received B and 17 received PLD + B. The RR (≥partial remission) was 5/14 (35.7%) and 5/17 (29.4%), respectively (P=0.73). Mean TTP was 297 days for B vs. not reached for PLD + B (P=0.93, HR 0.92, CI 95%). In patients with an abnormal baseline rFLC, 232 received B and 228 received PLD + B. The RR was 95/232 (40.9%) and 107/228 (46.9%), respectively (P=0.19). TTP was longer and statistically significant for patients who received PLD + B (282 days) vs. B alone (180 days; P=0.001, HR 1.76, CI 95%). For the overall population, TTP was 297 vs. 218 days (P=0.11, HR 0.51, CI 95%) and RR was 10/31 (32.3%) vs 202/460 (43.9%) for normal vs abnormal baseline rFLC groups, respectively. During the course of therapy, there was a trend for an increase in the percentage of patients in whom the baseline rFLC changed from abnormal to normal (Table). This trend occurred in earlier treatment cycles and reached a plateau in later cycles. When only patients who had completed at least 4 cycles of therapy were examined, the same trend was observed (not shown).

Conclusion

This study showed a correlation between the baseline rFLC and outcomes (TTP and RR) in patients with relapsed/refractory MM treated with PLD + B or B alone. Similar to the overall study results, combination therapy demonstrated better outcomes over B alone in patients with abnormal rFLC at baseline. Regardless of treatment, patients with normal rFLC at baseline had longer TTP but lower RR than patients with abnormal rFLC at baseline, which was possibly due to the small number of patients with normal rFLC at baseline.

Disclosures:

Londhe: Centocor Ortho Biotech Services, LLC: Employment, Equity Ownership. Lantz:Centocor Ortho Biotech Services, LLC: Employment. Lowery:Centocor Ortho Biotech Services, LLC: Employment, Equity Ownership. Sonneveld:Johnson & Johnson: Consultancy. Bladé:Johnson & Johnson / Janssen-Cilag: Honoraria; Schering-Plough: Honoraria.