Main Article Content
Objective: To study the predictive value of reduction of involved free light chain level on Day 21 of chemotherapy for achievement of VGPR after 4 cycles of induction chemotherapy.
Methods: We conducted a prospective observational study in twenty eight patients of newly diagnosed Multiple Myeloma with iFLC ≥ 100mg/L. Serum FLC assay was done at baseline and on day 21 of therapy. All patients were followed up till the end of induction therapy for response assessment based on the IMWG criteria. Receiver Operator Characteristic (ROC) curve analysis was done to determine the cut off value of percent reduction in day 21 iFLC for achievement of VGPR or better.
Results: After the induction chemotherapy, out of 28 patients, 13 patients achieved CR, 8 patients achieved VGPR, 4 patients achieved PR and 2 patients had stable disease (≥ VGPR = 21 patients, < VGPR = 6 patients). One patient expired after 2nd cycle of chemotherapy. The mean per cent reduction in day 21 iFLC level as compared to baseline was 91.5% and 57.1% in patients achieving ≥ VGPR and < VGPR (P < 0.0001), respectively. No other baseline parameter was found to be significantly different between the 2 groups. ROC curve analysis demonstrated a cut off of 84% reduction in iFLC value on day 21 (AUC of 0.937) had a sensitivity of 85.7% and a specificity of 100% in predicting the achievement of VGPR after four cycles of induction chemotherapy.
Conclusion: Monitoring iFLC levels on Day 21 can be used as an important tool for early identification of responders/non responders to myeloma therapy. We recommend serum FLC assay to be done on day 21 as a real time assessment of treatment response in newly diagnosed myeloma patients. Key words- Multiple Myeloma, involved Free Light Chain (iFLC), Very Good Partial Response (VGPR)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
- Rajkumar SV. Multiple Myeloma: 2018 update on Diagnosis, Risk-stratification and Management. American Journal of Hematology, 2018, 93(8): 981-1114. https://doi.org/10.1002/ajh.25117
- Katzmann JA, Clark RJ, Abraham RS, et al. Serum Reference Intervals and Diagnostic Ranges for Free and Free Immunoglobulin Light Chains: Relative Sensitivity for Detection of Monoclonal Light Chains. Clinical Chemistry, 2002, 9: 8. https://doi.org/10.1093/clinchem/48.9.1437
- Tacchetti P, Cavo M, Rocchi S, et al. Prognostic impact of serial measurements of serum-free light chain assay throughout the course of newly diagnosed multiple myeloma treated with bortezomibbased regimens. Leuk Lymphoma, 2016, 57(9): 2058-2064. https://doi.org/10.3109/10428194.2015.1124994
- Hansen CT, Pedersen PT, Nielsen LC, et al. Evaluation of the serum free light chain (sFLC) analysis in prediction of response in symptomatic multiple myeloma patients: rapid profound reduction in involved FLC predicts achievement of VGPR. European Journal of Haematology, 2014, 93(5): 407-413. https://doi.org/10.1111/ejh.12376
- Binding Site. A Laboratory Overview. https://www.bindingsite.com/en/our-products/freelite-and-hevylite/freelite/laboratory-information/a-laboratory-overview
- Snozek C, Katzmann J, Kyle R, et al. Prognostic value of the serum free light chain ratio in newly diagnosed myeloma: proposed incorporation into the international staging system. Leukemia, 2008, 22(10): 1933-1937. https://doi.org/10.1038/leu.2008.171
- Kyrtsonis M-C, Vassilakopoulos TP, Kafasi N, et al. Prognostic value of serum free light chain ratio at diagnosis in multiple myeloma. British Journal of Haematology, 2007, 137(3): 240-243. https://doi.org/10.1111/j.1365-2141.2007.06561.x
- Mead GP, Carr-Smith HD, Drayson MT, et al. Serum free light chains for monitoring multiple myeloma. British Journal of Haematology, 2004, 126(3): 348-354. https://doi.org/10.1111/j.1365-2141.2004.05045.x
- Dejoie T, Corre J, Caillon H, et al. Serum free light chains, not urine specimens, should be used to evaluate response in light-chain multiple myeloma. Blood, 2016, 128(25): 2941-2948.
- Dispenzieri A, Zhang L, Katzmann JA, et al. Appraisal of immunoglobulin free light chain as a marker of response. Blood, 2008, 111(10): 4908-4915. https://doi.org/10.1182/blood-2008-02-138602
- Mori S, Crawford BS, Roddy JV, et al. Serum free light chains in myeloma patients with an intact M protein by immunofixation: potential roles for response assessment and prognosis during induction therapy with novel agents.Hematological Oncology, 2012, 30(3): 156-162. https://doi.org/10.1002/hon.1019
- van Rhee F, Bolejack V, Hollmig K, et al. High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis. Blood, 2007, 110(3): 827-832. https://doi.org/10.1182/blood-2007-01-067728
- Hutchison CA, Cockwell P, Stringer S, et al. Early Reduction of Serum-Free Light Chains Associates with Renal Recovery in Myeloma Kidney. American Society of Nephrology, 2011, 22(6): 1129-1136. https://doi.org/10.1681/ASN.2010080857
- Sugihara H, Chihara D, Seike K, et al. Percentage of urinary albumin excretion and serum-free light-chain reduction are important determinants of renal response in myeloma patients with moderate to severe renal impairment. Blood Cancer Journal, 2014, 4(8): e235. https://doi.org/10.1038/bcj.2014.56