Publication Only: Myeloma and other monoclonal gammopathies - Clinical
MRD-negative status in patients with MM after auto-HSCT is considered as a favorable prognostic factor. Despite the absence of aberrant plasma cells according to flow cytometry data on the 100th day after auto-HSCT, early recurrence of the disease is observed in some patients. Considering the biological features of MM, which consists in diffuse focal lesion of the bone marrow, the study of the bones of the entire skeleton with visual assessment methods are of scientific value. MRI, as the most sensitive method for determining the infiltrative changes in the bone marrow, may become one of the additional criteria for an antitumor response.
To determine the effect of identified bone marrow lesions using MRI in MM patients who have MRD-negative status after auto-HSCT on progression-free survival (PFS).
14 patients with MM (7 male and 7 female) aged 46 to 66 years (median age 56 years) were enrolled in a prospective study in the period from December 2015 to March 2017. The ISS stages at the time of diagnosis were as follows: stage I in 5 patients, stage II in 6, and stage III in 3 subjects. Soft tissue components were observed in 6 patients (43%). All patients received induction therapy with bortezomib. Following induction therapy, single auto-HSCT was performed in 14 patients. MRI of the spine and pelvic bones was carried out with a GE Signa Profile system without contrast enhancement 100 days after auto-HSCT. The nature of the lesions was determined and the bone marrow infiltration lesions (≥ 5 mm) counted. Statistical analysis was done using Statistica 10.
After auto-HSCT, the following antitumour response rates were observed: CR in 10 (72%), VGPR in 2 (14%) and PR in 2 subjects (14%). At 100 days after auto-HSCT all patients achieved strict CR (MRD-negativity according to flow cytometry). Focal changes in the bone marrow by MRI after auto-HSCT were detected in 12 patients: the minimum number of lesions was 1, the maximum was 40 (average 6). The distribution of patients according to the number of lesions after auto-HSCT was as follows: 0 - 1 in 7 (50%) patients, 2 - 40 in 7 (50%) cases. After auto-HSCT patients did not receive maintenance therapy they were monitored until the disease recurred. With a median follow-up of 21 months, relapse was documented among 8 patients. At the same time, in 3 of them, the results of MRI performed on the 100th day after auto-HSCT showed minimal bone marrow damage (less than 1 focus) and in 5 cases more than 1 lesion of the bone marrow was detected.
3-year PFS in the group of patients with minimal bone marrow damage on MR-tomograms (less than 1 lesion) was significantly (p <0.05) higher and amounted to 52% versus 18% in the group of patients with more than 1 lesion detected in the bone marrow by MRI data (Figure 1).
Differences in PFS suggest that in patients with MRD-negativity after auto-HSCT, a whole-body MRI reveals focal lesions in the bone marrow. Flow cytometry examines only local bone marrow damage from a biopsy. MRI of the bone marrow can reduce the false-negative results of the determination of MRD after auto-HSCT.