Impact of sFLC Ratio on Outcome in Patients with MM: Validating the Utility of sFLC in Response Definition

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.3080-3080
• Main Authors: Abdallah, Nadine, Rajkumar, S. Vincent, Jevremovic, Dragan, Kapoor, Prashant, Dispenzieri, Angela, Gertz, Morie A., Lacy, Martha Q., Buadi, Francis K., Hayman, Suzanne R., Dingli, David, Muchtar, Eli, Gonsalves, Wilson I, Kourelis, Taxiarchis, Warsame, Rahma M, Siddiqui, Mustaqeem A., Go, Ronald S., Leung, Nelson, Hwa, Yi L., Hobbs, Miriam A., Fonder, Amie, Kyle, Robert A., Kumar, Shaji K.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-131835

Background: The treatment of Multiple Myeloma (MM) has evolved significantly in the past decade with the introduction of novel agents and drug combinations, thus enhancing treatment efficacy and allowing more patients to achieve complete response (CR). This has created a need to identify surrogates for depth of treatment response. Serum free light chain (sFLC) ratio normalization has been shown to be prognostic for progression free survival as well as overall survival in patients achieving a complete response to therapy. Consequently, it has been incorporated as a defining feature for stringent CR, along with lack of clonal plasma cells by immunohistochemistry (IHC) or low sensitivity flow cytometry. The routine use of multiparametric flow cytometry with higher sensitivity to detect residual disease than IHC or the older 4-color flow cytometry, has raised the question as to whether sFLC ratio is still a valid indicator of response depth. Moreover, in nearly half of the patients with an abnormal sFLC ratio after treatment, the abnormality is secondary to suppression of one or both serum light chains. Therefore, we designed a retrospective study to address these issues. Patients and Methods: This is a retrospective study using the Multiple Myeloma Database at Mayo Clinic, Rochester. We included patients who, after any line of therapy, had negative serum and urine immunofixation and absence of clonal bone marrow plasma cells by flow cytometry (PC-PRO), which has a sensitivity of >10-4. Simultaneous sFLC data was also extracted. Patients were grouped into three categories based on their sFLC ratios: 1) normal ratio (normal), 2) abnormal ratio due to suppression of the uninvolved light chain (LC), involved LC, or both (Abn-suppressed) and 3) abnormal ratio due to elevation of the involved LC (Abn-inv elevated). The primary endpoint was the median time to next treatment (TTNT), defined as the time from sample collection to the time of initiation of the subsequent therapy or time of last follow up if a subsequent line of treatment was not initiated. Results: The cohort consisted of 510 patients. 285 (56%) were males and 225 (44%) females. Median age was 61 years (IQR: 55-67). Median Follow-up was 41 months. The last treatments administered prior to data collection included stem cell transplant (SCT) (with or without maintenance) in 290 (57%) patients, and non-SCT regimens in the others. The sFLC ratio was normal in 337 (66%) and abnormal in 173 (34%) patients. Am