Magnetic resonance imaging (MRI) is increasingly being used to diagnose bone marrow lesions in patients with multiple myeloma (MM). Since 2014, the results of MRI have been included in the updated criteria of the International Myeloma Working Group. The presence of >1 bone marrow lesion larger than or equal to 5 mm on MRI is considered sufficient for the diagnosis of symptomatic MM, requiring initiation of treatment. MRI assessment of bone marrow is also possible with functional sequences such as diffusion-weighted imaging (DWI), which provide additional information about the bone marrow. This article provides an overview of the possibilities of MRI with anatomical sequences and with DWI for diagnosing, monitoring and evaluating the response to treatment in patients with MM. In patients with monoclonal gammopathy of undetermined significance and smoldering myeloma, in some cases, pathological changes in the bone marrow can be detected by MRI. The presence of >1 bone marrow lesion on MRI is a cut-off value as a prognostic factor for the progression of monoclonal gammopathy of undetermined significance or smoldering myeloma to symptomatic MM. In symptomatic MM, there are four patterns of bone marrow infiltration on MRI – focal, diffuse, “salt-and-pepper” infiltration, and combined diffuse and focal pattern, which have prognostic significance. Patients with diffuse pattern of infiltration on MRI had a 3-year overall survival of 35 % versus 92 % in patients with normal MRI bone marrow. During treatment of MM patients, residual bone marrow lesions are often identified on MRI. MRI residual bone marrow lesions increase the risk of MM relapse. In the group of patients who had residual bone marrow lesions on MRI on the 100th day after autologous hematopoietic stem cell transplant, 2-year progression-free survival was 50 % versus 89 % in patients without bone marrow lesions at the same time. The addition of DWI to the scan protocol helps to differentiate persistent focal bone marrow lesions that can lead to MM relapse after the treatment phase. Apparent diffusion coefficient is a quantitative indicator of DWI. MRI can serve as a valuable tool for assessing the treatment response in patients with MM.

AIMThis study conducted the possibilities of diffusion-weighted magnetic resonance imaging of the whole body diffusion WB-MRI (in comparison with positron emission tomography with computed tomography PET/CT) in assessing the volume and prevalence of the tumor, as well as determining bone marrow (BM) damage (for various cytological types) in the diagnosis and staging of the disease in patients with FL.MATERIALS AND METHODSA prospective comparative search study included 15 patients (4 men and 11 women, with a median age of 53 years) with newly diagnosed FL. Patients have not received antitumor chemotherapy previously. After the diagnosis was established, all patients (with the blindness of both the cases themselves and some specialists regarding the results of other specialists) were examined by PET/CT and diffusion WB-MRI, after which a BM examination was performed (histological examination and determination of B-cell clonality in BM puncture by PCR). Using the diffusion WB-MRI method, the prevalence of tumor lesion (nodal and extranodal foci) in each patient was estimated, and the total tumor volume was calculated, BM lesion was detected, and BM lesion volume was calculated. For lesions of different localization, the measured diffusion coefficient (DC) of the diffusion WB-MRI and the standardized rate of accumulation of the radiopharmaceutical in tissues (SUV) of the PET/CT method were determined and compared with each other (for the same areas). Statistical analysis was performed using the estimate of agreement (by Cohens kappa coefficient and asymptotic test) of the results of the compared methods.RESULTSEstimates of the prevalence of tumor damage (lymph nodes and extranodal foci) using the diffusion WB-MRI and PET/CT methods were the same. High DC and SUV were observed in the peripheral lymph nodes, extranodal foci and bulky, low DC and SUV in the foci of BM. All 4 methods successfully determined BM damage, however, the diffusion WB-MRI had comparatively less negative results. The highest values of SUV and CD were noted in cases of the 3 grade of FL. Using the diffusion WB-MRI method, the prevalence of tumor lesion was assessed in each patient (nodal and extranodal foci were detected) and the total tumor volume was calculated, BM lesion detection was performed, and the volume of BM lesion was calculated. It is important to note that with the help of diffusion WB-MRI, it was possible to measure separately the total tumor volume (462025 cm3) and separately the volume of bulky (251358 cm3). The diffusion WB-MRI allowed us to differentiate the volume of tumor tissue (reduced as a result of treatment) and residual (fibrous-adipose) tissue in residual formations (which averaged 21% of the initial volume). The predictors of a poor antitumor response were the maximum SUV values (more than 14.0) and the minimum DC values (0.510-3mm2/s) in the BM foci.CONCLUSIONThe diffusion WB-MRI allows for detailed visualization of BM lesions and surrounding soft tissues both in the debut of the FL and in the process of tracking the effectiveness of chemotherapy, which makes it possible to use it along with PET/CT. Diffusion WB-MRI allows to separately evaluate the volume of true tumor tissue and residual tissue. Cases of the 3 grade of FL (including the transformation of FL into diffuse B-large cell lymphoma) are isolated due to low DC values (and high SUV values) in the tumor tissue. BM foci of FL lesion also have (in comparison with nodal and extranodal foci) lower DC values. The predictors of a poor antitumor response were high (from 14.0 or more) SUV valuesin the tumor (and especially in bulky), and low (about 0.5103mm2/s) DC values of BM foci. The PET/CT and diffusion WB-MRI have proven to be reliable diagnostic tools for establishing the stage of FL and detecting BM damage. Diffusion WB-MRI for FL is an informative first-line diagnostic method that allows regular monitoring of the disease and early detection of foci of relapse and disease progression.

Poster: ECR 2020 / C-03990 / Whole body MRI with DWIBS for patients with plasma cell neoplasms: values of ADC depending on bone marrow patterns by: N. Lutsik , G. Yatsyk, L. Mendeleeva, M. Solovev, V. Savchenko; Moscow/RU

Introduction. Whole-body diffusion-weighted magnetic resonance imaging (MRI) is an informative method for bone marrow infiltration diagnosis in patients with multiple myeloma (MM) and post-monitoring in autologous haematopoietic stem cell transplantation (auto-HSCT).Aim: to study bone marrow lesions in MM patients using whole-body MRI prior to and after chemotherapy with subsequent auto-HSCT.Materials and methods. Forty patients with MM were included in a prospective study of whole-body MRI before and after high-dose chemotherapy with auto-HSCT. All patients had whole-body MRI prior to and at +100 day of auto-HSCT. Antitumour response was assessed after induction and at +100 day. The number and volume of bone marrow lesions prior to and at +100 day of auto-HSCT were determined, along with apparent diffusion coefficient (ADC) in the lesions.Results. We observed a significant reduction of 29 % in the number of lesions, 40 % — in their volume and 33 % — in ADC. A significant correlation was revealed between relative reduction in the number and volume of foci (r = 0.52, p = 0.0017). A correlation was found between relative reduction in the foci number and ADC (r = 0.47, p = 0.016). Patients with lesions > 7 cm3 in MRI data exhibited a lesser reduction in the foci number and volume and ADC values after auto-HSCT compared to patients with lesions < 7 cm3.Conclusion. Whole-body MRI with diffusion-weighted imaging and subsequent estimation of the number and volume of lesions and their ADC values prior to and after auto-HSCT add power to assessing antitumour response in MM patients with auto-HSCT.

Background: 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. Aims: 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). Methods 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. Results: 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).Summary/Conclusion: 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.

BACKGROUND: Follicular lymphoma (FL) is a B-cell tumor, which in most patients is characterized by slow growth and an "indolent" clinical course. In 80% of patients bone marrow is affected, which is a reflection of the pathogenesis of the tumor. The "watch and wait" tactic is a frequently used variant of patient management. For effective therapy, it is necessary to establish the stage of the disease, which requires the examination of the bone marrow (bilateral trepanobiopsy) and the identification of nodal and extranodal lesions (using PET/CT or CT of the whole body). The use of these methods is associated with high radiation exposure and the risk of complications in the intravenous radiopharmaceuticals and contrast agents. Whole body diffusion-weighted magnetic resonance imaging (WB-DWI) makes it possible to detect the burden of the tumor process without the use of contrast agents. AIM: Assess the capabilities of the WB-DWI method for determining the prevalence of a tumor and the detection of BM lesions in patients with FL. PATIENTS AND METHODS: The study was conducted during the fourth quarter of 2018 in the National Research Center for Hematology (Moscow), covered 8 patients (3 men and 5 women, with an average age of 53 years). According to the developed design of the study at the time of diagnosis of PL, all patients underwent a WB-MRI study, and then performed (with masking of participants): PET/CT, a histological examination of the bone marrow and the determination of B-cell clonality in bone marrow punctate (using PCR method). The results of the last two examinations were taken as reference (true) estimates for the detection of bone marrow lesions, and compared with the results obtained using the WB-MRI and PET/CT methods. Cohen's kappa statistical coefficient was used to assess the agreement between comparing methods. RESULTS: All 8 patients had a generalized lesion of the lymph nodes and extranodal foci (stage 4 according to An-Arbor). It was found that the measured diffusion coefficient in the lesions of the BM was 0,5‒0,9 х 10-3 mm/s. Reference tests showed that in 7 out of 8 patients, BM was affected. PET/CT gave two false-negative results, WB-DWI - one false-negative results (Tables 1‒2). Estimates of the prevalence of lesions of the lymph nodes and extranodal foci by WB-DWI and PET/CT were consistent with the accuracy of the methods. Estimates of the extent of lymph node involvement and extranodal lesions using WB-DWI and PET/CT were coincided with the accuracy of the methods errors. CONCLUSION: The results (Table 3.) of this exploratory research show that the WB-DWI method reveals a bone marrow damage not worse than the PET/CT method: kappa coefficient for WB-DWI was 0.6 and for PET/CT ‒ 0,5, respectively (due to the small sample size, strict statistical significance was not reached). WB-DWI allows you to quickly and informatively determine the affected areas and the involvement of BM, and thereby establish the stage of the disease. The results suggest an opportunity (along with the PET/CT method) to use the WB-DWI method as well. Disclosures No relevant conflicts of interest to declare.

Background . The study of influence of residual tumor mass, determined by magnetic resonance imaging (MRI), on the progression-free survival (PFS) remains an actual problem. Since the visual assessment of tumor bone marrow lesion can be one of the criteria for the subsequent personalized treatment choice in multiple myeloma patients.The objective of study was to determine the effect of bone marrow lesions detected by MRI after autologous hematopoietic stem cells transplantation (auto-HSCT) on PFS in multiple myeloma patients.Materials and methods . The prospective study included 60 patients who underwent spine and pelvic bones MRI on the 100 th day after autoHSCT.Results . Focal bone marrow changes were found in 47 of them – from 1 to 56 lesions (mean 6 ± 9). Significant (p = 0.01) differences of PFS in multiple myeloma patients depending on the presence or absence of tumor mass on 100 th day after auto-HSCT were revealed: with MRI negative status, 2-year PFS was 89 % versus 50 % in a group of patients with residual tumor mass.Conclusion . MRI-negative status after auto-HSCT is a favorable prognostic factor contributing to prolonged disease-free survival.

Introduction. Despite the availability of results from several studies that evaluated the role of magnetic resonance imaging (MRI) in the diagnosis of multiple myeloma (MM), data on the value of MRI after antineoplastic treatment, in particular after autologous hematopoietic stem cell transplantation (auto-HSCT), are limited. Objective. To study changes in bone marrow lesions using MRI in MM patients before and after auto-HSCT. Materials and methods. Forty patients with MM (15 male and 25 female) aged 36 to 66 years (median age 56 years) were enrolled in a prospective study. MRI of the spine and pelvic bones was performed before and 100 days after auto-HSCT to track bone marrow changes after transplantation. MRI was carried out with a GE Signa Profile system without contrast enhancement. The nature of the lesions was determined, and the bone marrow infiltration lesions (>= 5 mm) were counted. Results. MR images showed a decrease in the number of foci after auto-HSCT in 17 (52%) patients, and a reduction in the volume of the tumors in 29 (88%) patients. In most patients, even when a complete response (CR) was achieved, MRI revealed residual tumor load in the bone marrow, which decreased after auto-HSCT (by 1.4 times in the number of detectable lesions, and by 2.4 times in the tumor volume). Conclusion. By making it possible to evaluate the residual tumor load, whole-body bone marrow MRI can be used as an additional non-invasive method for assessing response to antitumor therapy in MM patients.

Aim. To evaluate the efficacy of maintenance therapy in multiple myeloma (MM) patients after autologous hematopoietic stem cell transplantation (auto-HSCT) based on the results of MRI of bone marrow. Materials & Methods. The study included 32 MM patients aged 36 to 66 years (median 57 years) with complete remission after a single auto-HSCT. MRI of spine and pelvic bones was performed to identify the nature of bone marrow lesions and to determine the volume of tumor tissue on the day 100 after auto-HSCT. As maintenance therapy after auto-HSCT 14 patients received daily 15 mg lenalidomide in the period from day 1 to day 21 of the 28-day treatment course within 1 year. Monitoring of 18 patients was conducted without maintenance therapy. Statistical analysis included the assessment of progression-free survival (PFS) and relapse risk relationship to clinical and laboratory parameters. Results. Twenty patients had a positive MRI (tumor volume > 1 cm3). Zero variation of MR signal in bone marrow and detection of a < 1 cm3 tumor were regarded as a negative MRI, which was the case in 12 patients. After reaching the negative MRI the best rates of 2-year PFS were registered: 100 % with maintenance therapy and 84 % without maintenance therapy. In patients with tumor load on MR scans the 2-year PFS significantly (p = 0.03) varied and accounted for 80 % in patients who received maintenance therapy vs. 33 % in patients without maintenance therapy. Administration of maintenance therapy after detecting residual tumor on MR scans on day 100 after auto-HSCT has a positive effect on PFS rates. Multivariate analysis confirmed the residual tumor on MR scans of bone marrow to be the most important parameter PFS depends on. Conclusion. A negative MRI after auto-HSCT is a favourable prognostic factor determining a long-lasting (> 2 years) MM free period, despite the lack of maintenance therapy.