When myeloma patients relapse, the clone type may differ to the type initially expressed at diagnosis. Early evidence of this was reported by Ayliffe et al. (1) in 2007. The study observed changes in the monoclonal protein production during the course of the disease. These patients initially expressed intact immunoglobulin, but later produced only FLC. Similar changes in monoclonal protein expression have been reported in many other studies over the years for all myeloma types (2-5).
Zamari et al. (6) examined the frequency of clonal change at relapse in 126 myeloma patients, tested with SPE and sFLC, using Freelite assays, at diagnosis and relapse. Overall, it was reported that 44% of patients changed their monoclonal protein type at relapse, 56% express FLC at relapse and 22% undergo light chain escape.
Looking at the different relapse patterns:
- All patients with LCMM relapsed with only FLC expression at relapse. Therefore, it seems that clones that have heavy chain expression switched off at diagnosis do not switch it back on and this “switching off” is a terminal event.
- Among patients that expressed both FLC and intact immunoglobulins at diagnosis, 40% relapsed with production of intact immunoglobulin only, 22% relapsed with light chain production only.? This 22% were the patients with LC escape.
- Among patients that were expressing intact immunoglobulins only at diagnosis, almost 20% of these patients started to produce FLC as well as intact immunoglobulins at relapse.
?Figure 1: Evolution of the types of monoclonal protein present at diagnosis and at relapse or progression of disease.
An enhanced follow-up, including sFLC testing, will help identify the different patterns of relapse for all multiple myeloma patients.
- Ayliffe et al. Demonstration of changes in plasma cell subsets in multiple myeloma. Haematologica. 2007 Aug;92(8):1135-8. doi: 10.3324/haematol.11133. PMID: 17650446.
- Hobbs et al. Frequency of altered monoclonal protein production at relapse of multiple myeloma. British Journal of Haematology, 2010, 148: 659-661.
- Patel et al. Nonsecretory and light chain escape in patients with multiple myeloma. Clinical Lymphoma, Myeloma & Leukemia. CLML. 2018.
- Migkou et al. Clinical characteristics and outcomes of oligosecretory and non-secretory multiple myeloma.?Ann Hematol?99, 1251–1255 (2020).
- Drayson et al. Serum free light-chain measurements for identifying and monitoring patients with non-secretory multiple myeloma. Blood. 2001 May 1;97(9):2900-2.
- Zamarin et al. Patterns of relapse and progression in multiple myeloma patients after auto-SCT: implications for patients' monitoring after transplantation. Bone Marrow Transplant. 2013 Mar;48(3):419-24.
