Multiple Myeloma Oligosecretory Relapse: A Cross-Sectional Historical Cohort Study

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Presence of monoclonal antibodies in the serum and/or urine, secreted by malignant plasma cells is the hallmark of multiple myeloma (MM), and central in disease diagnosis and monitoring. Yet, infrequently, monoclonal protein (M-protein) and involved free light chain (iFLC) are either not detected or are both below the threshold for measurable disease, termed oligo-secretory MM. The incidence of oligo-secretory MM at presentation has been estimated at 1-2%, yet data regarding the frequency and clinical phenotype of oligo-secretory relapse (OSR) are lacking. Aims: We report the characteristics and outcomes of OSR. Methods: Patients (Pts) were classified as having an OSR if they had a non-measurable disease (M-protein<1 gr/dL, and U-PEP <200 mg/24 hrs and iFLC< 10 mg/dL) at the time a relapse, based on new or increasing lesion(s), increase in bone marrow or circulating plasma cells (PCs), according to IMWG criteria. All consecutive MM pts who had measurable disease at diagnosis and developed an OSR between January 2016 to July 2020, across two centers (Mayo Clinic Rochester, US and Tel Aviv Sourasky medical center Israel (TLVMC) were included. The first OSR that any given pt experienced was defined as the index OSR for that pt. For each pt with an OSR, we identified a pt with a secretory relapse (SR) in the dataset, matched by the relapse index number, calendar year of relapse, and medical center, to form a SR comparator group. We compared pt and disease characteristics at MM diagnosis and at relapse, therapy patterns, and outcomes between the OSR and SR groups. Results: Fifty-seven pts with an OSR were identified; 40 in Mayo Clinic and 17 in TLVMC. At diagnosis, pts with OSR were younger, their iFLC was more frequently kappa, they had more frequently IgA heavy chain, LC levels were lower, % bone marrow PCs was lower, and renal failure was less frequent (Table). There were no differences between the groups in terms of FISH cytogenetics, RISS, levels of M-protein, and the frequency of extramedullary disease. Treatment patterns and responses to upfront therapy were comparable. Most (66.6%) OSR occurred in early relapses (first (n=21) or second (n=17). OSR pts had higher rates of new lesions or increase in lesion size as relapse criteria; renal failure was more frequent in SR pts. Median follow-up was 3.85 years (range 0.5-9.5). Overall response rate was none evaluable in over a third of OSR pts. TTNT was 15 (95%CI 6.5-23.5) vs 8 (3.22-12.78) months (p=0.187), and the median overall survival was 3.44 vs 3.25 (p=0.785) in OSR and SR, respectively. Summary/Conclusion: MM characteristics at diagnosis for pts that developed OSR were different than SR matched controls: OSR pts were younger, had a lower iFLC and PC infiltration, and had kappa predominance, suggesting an inherent biological difference associated with attenuation of immunoglobulin production at relapse. OSR presented with worse bone disease and extramedullary lesions, and response assessments were frequently unavailable in these pts, probably reflecting the challenge of effective monitoring of disease response in the absence of laboratory biomarkers. Improved monitoring strategies for OSR pts are warranted.Keywords: Myeloma