Bone marrow MRI after autologous transplantation and the effect of residual tumor on progression-free survival of multiple myeloma patients

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

Survival analysis of patients with uveal melanoma after organ preserving and liquidation treatment

Rationale: Uveal melanoma is the most common primary malignancy of the eye.Aim: To evaluate survival in patients with uveal melanoma stratified according to the type of treatment and to identify factors significantly associated with their survival.Materials and methods: The study was performed on the data extracted from medical files and follow-up forms of patients with uveal melanoma seen in the Ophthalmological Clinical Hospital of the Department of Healthcare, Moscow, from 1977 to 2012. Analysis of survival was used to assess the life longevity of patients with uveal melanoma. The analysis was censored at January 2013, when vital status (dead or alive) of all patients was assessed. The factors included into the study analysis, were those taken from the follow-up forms. The incidence of uveal melanoma in Moscow (2012) was 0.9 per 100,000 of the population, whereas its prevalence was 11.1 per 100,000.Results: 698 patients with uveal melanoma were included into the study, among them 260 (37%) men (aged from 19 to 87 years, median age 60 years) and 438 (63%) women (aged from 18 to 93 years, median age 63 years); therefore, the proportion of women under the follow-up monitoring was by 26% higher than that of men. The liquidation treatment (mostly enucleation) was performed in 358 (51%) of the patients, whereas the organ preserving treatment in 340 (49%). At 5, 7, and 10 years of the follow-up, the disease-specific survival of patients with uveal melanoma after the organ preserving treatment (median survival has not been reached) and after the liquidation treatment (median, 88 months) were 89 ± 2, 83 ± 3, and 75 ± 4% versus 63 ± 3, 52 ± 4, and 47 ± 5%, respectively (р = 0.001). Overall survival and disease-specific survival of the patients after the liquidation treatment were significantly lower than in the patients after the organ-preserving treatment. According to multiple regression analysis, this was associated not with the type of treatment, but rather with higher initial grade of the disease (as the most significant factor) and with older age (> 65 years; the second significant factor). Both factors were significantly more prevalent (р = 0.05; chi-square test) among the patients who underwent the liquidation treatment.Conclusion: The large size of the uveal melanoma, with its pre-equator location and extrascleral spread, as well as the age above 65 years can be considered as unfavorable prognostic factors

Follicular lymphoma: results of multicenter study of first-line therapy with bendamustine and rituximab, risk factors for adverse events (fl-rus-2013 protocol)

Background. Follicular lymphoma (FL) is the most common type of indolent lymphomas and accounts for 20–30 % of all non-Hodgkin’s lymphomas detected. High risk of recurrence and elderly patients make it difficult to choose induction therapy for FL. The R–B course in comparison with the R–CHOP course increases the progressive free survival (PFS) of FL patients and is less toxic. International studies have not studied the efficacy and toxicity of the R–B course due to various cytological types of FL.Aim of the study – assessment of the effectiveness and toxicity of the R–B course (with R support) in general and depending on the different cytological types of FL, the assessment of overall survival (OS) and PFS (adverse events: progression, relapse, death); identification of risk factors for an adverse event in general and death, in particular. The main endpoint of this study is selected BPV.Materials and methods. We performed a prospective, multicenter, open-label trial in Russia since June 1, 2013 till June 1, 2018. The study included 74 patients with FL. Median age of patients was 59 years (from 30 to 78 years). Treatment was completed in 66 patients, so this group of patients was analyzed. Ratio between men and women was 1:2. 32/66 of patients (48 %) were older than 60 years old. Patients received rituximab 375 mg/m2 on day 1 and bendamustine 90 mg/m2 on days 1 and 2 of a 4-week cycle (6 cycles). 49/66 (74 %) of patients were diagnosed with FL grade 1, 10/66 (15 %) – grade 2, 7/66 (11 %) – grade 3A. 34/66 (52 %) patients had nodular tumor growth type, 28/66 (42 %) – nodular-diffuse, 4/66 (6 %) – diffuse. High risk according to FLIPI had 25/59 (42 %) of patients with cytologic grade of FL 1–2 and 7/7 (100 %) of patients with FL grade 3A. Extranodal lesions were revealed in 26/66 (39 %) of cases: in 4/66 of cases – orbit, in 2/66 – parotid gland, in 5/66 – lungs, in 4/66 – intestines, in 2/66 – stomach, 2/66 – pancreas, 2/66 – uterus, 2/66 – skin, 1/66 – subcutaneous tissue, 3/66 – vertebrae, in 1/66 – latticed maze and nasal passages, 1/66 – kidneys, 1/66 – root of the tongue. In 23/26 (88 %) of cases extranodal lesion was revealed in generalized stage of FL (including lymph nodes and bone marrow). Extranodal lesions were found in 37 % of patients with FL grade 1–2, and 57 % with FL grade 3A. Bulky also was observed more frequently in pts with FL grade 3 3/7 (43 %) than in patients with FL grade 1–2 20/59 (34 %). (The risk factors of an adverse event are also its predictors in this study.)Results. Complete remission of disease was achieved in 40/66 (61 %) patients, partial remission – 13/66 (19 %) patients. Tumor progression observed in 11/66 (17 %) cases, patients were withdrawn from the protocol. А partial tumor response was achieved in 2/66 cases (3 %) and patients received high-dose therapy after 4 courses of R–B. Five-year (as well as the 3-year) overall survival (OS) of all patients (n = 66) in R–B was 90 % (95 % confidence interval (CI) 78–96), 5-year PFS – 70 % (95 % CI 55–85) and a 3-year PFS – 75 % (95 % CI 60–89). The cumulative incidence of relapse (considering competing risks of progression and death) at the 3th year after initiation of treatment was 11 % (95 % CI 3–19). The following independent statistically significant (p ≤0.05) predictors of PFS (measured in the onset of the disease) were determined (as a result of a stepwise multivariate cox regression analysis): 1) cytological type of tumor (only type 3A is significant); 2) involvement of nodal zones (more than 4); 3) presence of a conglomerate of tumor lymph nodes larger than 6 cm (bulky); 4) Ki-67 protein expression (more than 35 %). The first 3 characteristics (as well as the sign «presence of extranodal foci», close to the level of significance) are independent statistically significant predictors of OS. In the single factor analysis the following characteristics (besides the above) were significant: index FLIPI (significant only 5 points against all others), bone marrow damage, β2-microglobulin (more than 2.2 mg/L), age (over 68 years) and hemoglobin (less than 110 g/dL).Conclusion 1. The independent negative predictors of OS and PFS in follicular lymphoma were determined. 2. Of the predictors of an adverse event identified, the greatest risk (as a result of a multivariate analysis) is associated with a 3A cytological type of tumor. 3. The FLIPI index has a predictive value not only for the determination of OS, but also for the PFS (moreover, in reduced dichotomous form: 5 points against all the others combined). 4. An increase in the time interval between the first manifestations of follicular lymphoma (lymph node enlargement / appearance of a tumor formation) and the start of therapy beyond a certain threshold value (estimated to be approximately 22 months) is associated (according to the results of univariate analysis) with an increased risk of an adverse event. One of the reasons for the increase in this time interval is associated with expectant medical tactics adopted during the slow development of the clinical picture of the disease. The obtained result shows that the low rate of development of the clinical picture of the disease does not correlate with the low risk of adverse events, and, therefore, cannot be a determining factor when deciding whether to start treatment. 5. The morphology of the tumor is the determining factor in the choice of induction therapy. 6. After achieving full/partial remission of FL, there is a constant risk of recurrence of the disease (by the age of 3 from the termination of treatment, the risk is 11 % (95 % CI 3–19)). 7. The R–B course effectively sanitizes the bone marrow. 8. The R–B allows performing stem cells mobilization and autoSCT that is actual in FL patients with bone marrow involvement. 9. The treatment regimen of R–B is effective and has a relatively low toxicity, so it is advisable in the treatment of elderly patients

ESICM LIVES 2016: part two : Milan, Italy. 1-5 October 2016.

Meeting abstrac