Regular Follow-Up of MGUS Allow Early Detection of Malignant Transformation Before Severe Complications Occur.
Authors: Decaux Olivier , Besnard Sophie , Perlat Antoinette , Cazalets Claire , Cador Berengere , Sebillot Martine , Jego Patrick , Grosbois Bernard 
Published: October 2019

Abstract
Background: Monoclonal gammapathy of unknown significance (MGUS) is a frequent disorder that carries a 1% per year risk of progression to multiple myeloma (MM). Patients should be monitored annually to detect malignant transformation before complications occur.
Objective: To assess if MGUS regular follow-up allow early detection of malignant transformation before severe complications occur. Progression to multiple myeloma was established according to the criteria defined by the International Working Group. Criteria for severe complication were: hypercalcemia (> 3 mmol/l), acute renal insufficiency needing dialysis, bone fracture, sepsis.
Methods: We retrospectively reviewed medical data of patients treated for post-MGUS multiple myeloma in Internal Medicine Departement of Rennes University Hospital (France) between 1980 and 2006.
Results: Forty two patients were identified (23 men and 19 women). Median age was 66 years old (49 – 79) at the time of MGUS diagnosis and 70,5 years old (51 – 84) at the time of MM diagnosis. Isotype was: IgG in 37 patients (88%), IgA in 2 (5%) and biclonal IgG/IgA in 3 (7%). Median level of monoclonal component was 19,9 g/L (4,9 – 42,2) at MGUS diagnosis and 35,3 g/L (15,2 – 68) at the time of MM diagnosis. Median bone marrow plasmocytosis was 4% (0–10) for MGUS and 12% (1–30) for MM. Median time from MGUS diagnosis to malignant transformation was 4 years (1 – 12). Anemia (hemoglobin concentration ≤12 g/dL) was present at the time of MM diagnosis in 16 (38%) patients. It was generally moderate in severity; only 6 (14,2%) patients had a hemoglobin value of 10 g/dL or less and no patients had a haemoglobin value of 8 g/dL or less. The serum creatinine level was increased (more than 100 μmol/L) in 6 (14,2%) patients and no patients had a serum creatinine value of 200 μmol/L or more at the time of MM diagnosis. Two patients had an hypercalcemia (2,60 mmol/L or more) at the time of MM diagnosis. In 30 patients (71%), malignant transformation was detected before a severe complication occurs. In 8 patients (19%) a severe complication occurred before multiple myeloma diagnosis: hypercalcemia (2 cases), sepsis (2 cases), spinal fracture with epiduritis (3 cases), spontaneous sternum fracture (1 case). Four of these patients had refused follow-up and were not monitored for MGUS evolution despite medical explanations as regards to the risk of malignant transformation. In 4 patients (10%) criteria of MM diagnosis were not found in medical file because diagnosis was made in another hospital.) Most patients were treated with conventional chemotherapy (40% with MP) and two with autologous hematopoietic stem cell transplantation. The median survival after malignant transformation was 48 months.
Conclusions: Regular follow up of patients with MGUS allows earlier diagnostis of MM and prevent them for severe complications. We plan to compare this group with patients treated in our department for de novo MM during the same period of time.