M-protein Type Research Articles

Impact of Monoclonal Protein at Diagnosis on Outcomes in Patients with Marginal Zone Lymphoma: A Multicenter Cohort Study

Introduction Marginal zone lymphoma (MZL) is an indolent B-cell non-Hodgkin lymphoma that includes 3 subtypes: extranodal marginal zone lymphoma (EMZL) of the mucosa-associated lymphatic tissue (MALT), splenic MZL (SMZL), and nodal MZL (NMZL). Outside of case reports and small case series, the relevance of monoclonal protein (M-protein) in patients with MZL at diagnosis is largely unknown. Hence, we sought to evaluate the impact of M-protein at diagnosis on outcomes in patients with MZL. Methods This multicenter, retrospective cohort study of MZL patients treated at 8 US medical centers included patients who were ≥18 years old, diagnosed with MZL from 2010-2020, and had information on M-protein at diagnosis. Patients who were on observation or received antibiotics only were excluded. Patients were grouped according to the presence or absence of M-protein detectable by serum protein electrophoresis or immunofixation. The primary endpoint was progression-free survival (PFS). Secondary endpoints were time from diagnosis to systemic therapy, cumulative incidence of relapse in stage 1 disease after local treatment (surgery or radiation therapy), and cumulative incidence of transformation in M-protein versus no M-protein groups. PFS was defined as the time from the start of first-line therapy until lymphoma relapse/progression or death from any cause, censoring at the last clinical assessment. Results Among 501 eligible patients with newly diagnosed MZL, 152 (30%) had detectable M-protein at diagnosis and 349 (70%) did not. Among those with M-protein, 59% (n=90) had IgM, 29% (n=44) had IgG, 3% (n=4) had both IgM and IgG, and 9% (n=14) had non-IgM/non-IgG M-protein and light chains. Patients in the M-protein group had a higher median age (66 vs 61 years), more advanced stage disease (76% vs 53%), lower albumin (27% vs 15%), and were more likely to receive R-chemotherapy (39% vs 23%) compared to no M-protein group. The median PFS was 3.2 years (95%CI=2.1-5.6) in the M-protein group compared to 6.6 years (95%CI=5.4-NR) in the no M-protein group (log-rank p<0.001; Figure 1) with a 3-year and 5-year PFS rates of 51% and 44% in the M-protein gp versus 74% and 59% in the no M-protein groups. In order to determine if the M-protein was independently associated with PFS, we performed Cox regression analysis in only those who received systemic therapy at diagnosis (n=377). After adjusting for factors associated with PFS in univariate analysis (age, MZL subtype, ECOG PS, albumin level, LDH>ULN, and first-line treatment regimen), M-protein remained associated with significantly inferior PFS (HR=1.80, 95%CI=1.24-2.62, p=0.002) in the multivariable analysis. There was no difference in PFS based on the type of M-protein at diagnosis (IgM vs IgG, p=0.88). M-protein group treated with rituximab monotherapy had significantly shorter PFS compared to no M-protein group (1.9 years versus 4.3 years, p<0.001, Figure 2), however, there was no significant difference in PFS among patients treated with bendamustine and rituximab (BR, 6.1 years versus NR, p=0.14). In the EMZL subset (n=101) treated with local therapy (surgery or radiation), PFS did not significantly differ by presence/absence of M-protein at diagnosis (p=0.53). There was no difference in the time from diagnosis to systemic therapy initiation between the M-protein and no M-protein groups with % of patients who started treatment at 1, 3, and 5 years being 89% vs 86%, 96% vs 94%, and 99% vs 98%, respectively (p=0.21). The cumulative incidence of relapse in stage 1 disease (n=144) among the recipients of local therapy was not significantly different between the M-protein and no M-protein groups (p=0.10). The cumulative incidence of transformation was significantly higher in the M-protein group compared to no M-protein group with 3-, 5-, and 10-year rate of transformation being 5.6% vs 0.6%, 8.9% vs 1.3%, and 14% vs 1.3%, respectively (p=0.001). Conclusions In this study (to our knowledge, the largest to date) of the prognostic relevance of M-protein in MZL, we found that M-protein at diagnosis was associated with shorter PFS and a higher risk of histologic transformation. Because the PFS difference was not observed after BR, immunochemotherapy may be a preferred approach over rituximab monotherapy in this group and needs to be explored further. M-protein in stage 1 EMZL was not associated with shorter PFS after standard local therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Pre-treatment neutrophil to lymphocyte ratio as a biomarker of frailty and predictor of survival among older adults with multiple myeloma

IntroductionNeutrophil to Lymphocyte Ratio (NLR) combines a marker of inflammation and reduced cell turnover to reflect age related alterations in the immune system. Whether NLR can serve as a biomarker of frailty and predict survival among older adults with Multiple Myeloma (MM) is unknown. Materials and methodsWe used an electronic health record-derived database to identify older adults (age ≥ 60y) with incident MM diagnosed between 1/2011 and 2/2020, with known pre-treatment absolute neutrophil and lymphocyte count up to 90 days before the start of therapy. The calculated NLR values were stratified into quartiles (Q1-Q4). We constructed a previously validated, simplified frailty index combining age, comorbidity and ECOG performance status. We measured the association between NLR quartiles and this frailty index using a logistic regression, adjusted for age, sex and race/ethnicity. We used Kaplan Meier methods and multivariable Cox regression to assess the impact of NLR on overall survival adjusting for potential confounders. ResultsWe identified 1729 older adults with newly diagnosed MM, at a median age of 73y (IQR: 67-78y). The median NLR was 2.13 (IQR: 1.44 to 3.31). Of the 1135 evaluable patients, 55% met criteria for frailty. Multivariable analysis revealed a 2.1-fold higher odds of frailty (95%CI = 1.42–3.10, p < 0.001) for patients in the NLR Q4 group vs. NLR Q1 group. In a multivariable analysis, adjusting for age, sex, race/ethnicity, M-protein type, stage, high risk cytogenetics, baseline creatinine, LDH and type of first line therapy, patients in NLR Q4 group had a 1.51 times increased hazards of death (95%CI = 1.15–1.98, p 0.002) when compared to those in NLR Q1 group. ConclusionNLR, a readily available laboratory biomarker, is associated with frailty measured using a simplified frailty index as well as inferior overall survival among older adults with MM. Future studies should explore its value as a screening tool to identify frail older adults with MM.

Bortezomib, Lenalidomide and Dexamethasone (VRD-GEM) As Induction Therapy Prior Autologous Stem Cell Transplantation (ASCT) in Multiple Myeloma (MM): Results of a Prospective Phase III Pethema/GEM Trial

Bortezomib, Lenalidomide and Dexamethasone (VRD-GEM) As Induction Therapy Prior Autologous Stem Cell Transplantation (ASCT) in Multiple Myeloma (MM): Results of a Prospective Phase III Pethema/GEM Trial

Bortezomib, Liposome Doxorubicin and Dexamethasone (PDd) Is Superior in Safety and Not Inferior in Efficiency to Bortezomib, Doxorubicin and Dexamethasone (PAd) As Induction Therapy in New-Diagnosed Multiple Myeloma Patients: An Interim Report from China's Multicenter Study

Purpose:Bortezomib, doxorubicin and dexamethasone (PAd) and bortezomib, liposome doxorubicin and dexamethasone (PDd) are widely used as induction chemotherapy regimens in china in the new-diagnosed multiple myeloma patients before autologous stem cell transplantation or other consolidation therapy. There was no data on the comparison in safety and efficiency between that two regimens, so we design this open-label, randomized, multicenter clinical trial in China's 16 sites. Here is our interim report.Method:Until April 15th 2017, 18 cases with PDd and 22 cases with PAd have finished the whole induction therapy. Incidence of adverse reaction, therapeutic effect evaluation is compared here.Results:There is no significant difference in age, gender, ISS stage, R-ISS stage, D-S stage between the two groups. There is also no differences in the incidence of the M-protein type between the two groups except for IgA type more often in PAd group than PDd group (7/22 vs 1/18, p=0.0537). As the 40 patients finished the 4-cycle induction therapy, effect evaluation by morphology, IFE and FLC shows no difference in sCR, CR, VGPR, PR, SD, PD, as well as in ORR. And minimal residual disease tested by flow-cytometry is also no difference between the two groups. The incidence of leukocytopenia (III-IV°) (1/18 vs 9/22, p=0.0126) and thrombocytopenia (III-IV°)(2/11 vs 11/22, p=0.0162) is lower in PDd group than in PAd group, and no difference is observed in other adverse reactions such as active infection, neutropenia, anemia, febrile neutropenia, hepatic and renal impairment, herpes, ect.Conclusion:There is no difference in the efficiency after 4-cycle induction chemotherapy between the PDd group and PAd group, and PDd regimen show advantages in less incidence in leukocytopenia and thrombocytopenia. DisclosuresNo relevant conflicts of interest to declare.

Clinical Outcomes of Non-Traditional Lenalidomide, Bortezomib, and Dexamethasone Regimens in Multiple Myeloma

Introduction Lenalidomide, bortezomib, and dexamethasone (RVD) is a standard first-line regimen for patients with newly diagnosed multiple myeloma and is associated with high response rates and improvement in progression-free survival and overall survival compared to traditional chemotherapy regimens. Traditional (RVD Classic, RVD Lite) and non-traditional (RVD Premium Lite, RVD Ultra Lite) variations of the RVD regimen are utilized at Dana-Farber Cancer Institute (DFCI) and have not been fully evaluated in terms of safety and tolerability. RVD Premium Lite is administered in a 28-day cycle with weekly bortezomib; whereas, RVD Ultra Lite administers three weekly doses of bortezomib instead of four (Table 1). These two regimens have not been fully evaluated in terms of safety, tolerability, and efficacy. Selection is based on provider preference in addition to flexibility of dosing schedule. The regimens also allow for convenience of weekly dosing while keeping dose intensity. This retrospective, descriptive analysis is the first study to explore the safety, tolerability, and efficacy of four different RVD regimens used at DFCI. Methods This single-center, retrospective, descriptive analysis identified 90 newly diagnosed patients with multiple myeloma treated at DFCI main campus for &amp;gt;2 cycles of an RVD-based regimen in the front-line setting. We reviewed patients started on treatment from January 2017 to December 2019. Patients were excluded if treated primarily at an outside institution or satellite campus. Results A total of 90 patients were included between January 2017 to December 2019, and median age was 69.5 years (range 44-87). Most patients had either standard-risk or unknown cytogenetics. Of the 44 patients with available International Staging System (ISS) information, the majority were R-ISS/ISS I or II. The most common M-protein type at diagnosis was IgG (56.7%), followed by light chain restricted disease (25.6%). In terms of traditional and non-traditional RVD regimens, most patients received RVD Classic (33.3%) or RVD Ultra Lite (32.2%), followed by RVD Lite (23.3%) and RVD Premium Lite (11.1%). Patients in RVD Lite and RVD Ultra Lite groups were of older age when compared to the RVD Classic group (P&amp;lt;0.001). Lenalidomide dosing delays and reductions trended higher in the RVD Classic regimen at 14.3%, followed by RVD Ultra Lite at 12.3%. Bortezomib dosing delays and reductions were similar between the RVD Lite and RVD Classic regimens at 11.8% and 11.2%, respectively. Overall, combined lenalidomide and bortezomib dosing delays/reductions trended higher in the RVD Classic (14.3%/11.2%) and RVD Lite (11.0%/11.8%) compared to RVD Ultra Lite (12.3%/9%) and RVD Premium Lite (10.8%/9.6%). The most common toxicities noted with all variations of the RVD regimen were peripheral neuropathy, cutaneous toxicity, infection, diarrhea, and constipation. The highest rates of adverse events among all RVD regimens were infection and peripheral neuropathy. Peripheral neuropathy was slightly higher in the RVD Premium Lite and RVD Classic regimen at 8.43% and 8.70%, respectively, compared to RVD Lite and RVD Ultra Lite at 7.1% and 7.7%, respectively. No significant difference in toxicities were seen when regimens were compared (p=0.1369). Intolerance leading to therapy change trended higher in the RVD Lite group at 23.8%, followed by RVD Classic and RVD Ultra Lite at 16.7% and 10.3%, respectively. Nineteen percent of patients in the RVD Lite group had minimal response or progression leading to therapy change, which was highest among all RVD regimens. Rate of transplant was highest in the RVD Classic group at 36.7%, followed by RVD Premium Lite at 20%. There was no significant difference in intolerance, minimal response or progression, maintenance, continued induction or planned change, transplant, and death between regimens (p=0.089). In terms of progression-free survival, no differences were seen between the groups (p=0.36). Conclusion In conclusion, the current investigation allowed us to assess the safety, tolerability, and efficacy of traditional and non-traditional variations of the RVD regimen in multiple myeloma used at our institution. There are minimal differences between each regimen when toxicities are managed appropriately. Disclosures Richardson: Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding. Mo:Celgene/BMS: Membership on an entity's Board of Directors or advisory committees.

Effect of rFLC and dFLC on Clinical Prognosis of Patients with Newly Diagnosed Multiple Myelome and Best Cutoff Value

To investigate the influence of rFLC and dFLC on clinical prognosis and best cutoff value in patients with newly diagnosed multiple myelome(MM). Clinical data of 240 patients with newly diagnosed MM treated in Western Theater General Hospital of People's Liberation Army from January 2010 to June 2016 were collected and retroanalyzed. All patients were divided into different groups according to the interquartile spacing levels of rFLC and dFLC, the median OS and PFS of patients in different groups were compared. The influencing factors of prognosis in newly diagnosed MM patients were analyzed by univariate and multivariate methods, the influence of different cutoff values of rFLC and dFLC on clinical prognosis were evaluated. The median progression-free survival time of female patients with M-protein IgA type and I stage for ISS stage were significantly longer than those of male, other M-protein types and other ISS stage（P<0.05）. The median OS of patients without hypercalcemia was significantly higher than that of patients with hypercalcemia（P<0.05）. The median progression-free survival(PFS) time of patients with dFLC <110.95 mg/L was significantly longer than that of patients with dFLC=110.95-2 781.44 mg/L and >2 781.44 mg/L（P<0.05）. The median overall survival time of patients with dFLC ＜110.95 mg/L and ＞2 781.44 mg/L was significantly longer than that of patients with dFLC=110.95-2 781.44 mg/L（P<0.05）. The median overall survival time of patients with rFLC <14.71 mg/L was significantly longer than that of patients with rFLC >14.71-367.96 mg/L and >367.96 mg/L（P<0.05）. Univariate analysis of Cox regression model indicated that dFLC at all levels showed higher influence on the OS and PFS of patients as compared with rFLC（P<0.05）. Multivariate analysis of Cox regression model showed that rFLC and dFLC expression level were the independent prognostic factors of patients（P<0.05）. The most significant influence value on clinical prognosis of patients were observed when rFLC level ≤14.71 or dFLC level ≤110.95 mg/L（P<0.05）. The median OS of patients with rFLC level ≤14.71 was significantly higher than that of other groups（P<0.05）. There was significant difference in median PFS between patients with rFLC ≤14.71 and ≥367.96 mg/L（P<0.05）. The median OS and PFS of patients with dFLC ≤110.95 mg/L were significantly longer than those in other two groups（P<0.05）. The levels of rFLC and dFLC closely relate to clinical prognosis of patients with new diagnosed MM; the risk of recurrence or death is lowest in patients with rFLC level ≤14.71 mg/L or dFLC level ≤110.95 mg/L, which can be used as the ideal cutoff value for prognosis evaluation.

Multiple Myeloma of the Young - a Single Center Experience Highlights Future Directions.

Multiple myeloma is quite uncommon in the young population. We performed a retrospective review in our database from 2006 to 2015 to examine the clinical features, outcomes and survival of multiple myeloma patients ≤40years old. Among 312 newly diagnosed patients we found sixteen (5.1%) who were 40years old or younger. Their characteristics including M-protein type, genetical alterations, clinical symptoms and disease stage were as various as those in the older population. All but two young patients underwent autologous stem cell transplantation after the induction treatment. Their response to treatment did not differ markedly from the older patients. We also compared the survival data of patiens ≤40years and > 40years old. The 5-year progression-free survival were 48% and 35%, the 5-year overall survival were 83% and 53% respectively, the latter showing a significant advantage for the younger population. 70% of the young patients received maintenance or consolidation therapy after the initial treatment. Although several effective new therapies have been introduced recently, there is still an unmet need for curative treatment options for young and fit multiple myeloma patients.

Abstract 2639: Survival prognosis of MGUS patients by clinical and risk subgroup: a result from a nationally representative prospective cohort

Abstract Introduction: Monoclonal gammopathy of unknown significance (MGUS) is a premalignant disorder preceding multiple myeloma that is present in 2.4% of the general population ages 50 years or older. MGUS can be categorized into conventional MGUS that includes IgM MGUS and non-IgM MGUS, and light chain MGUS (defined as those with abnormal free light chain ratio with complete lack of immunoglobulin heavy chain expression on immunofixation). Our objective was to investigate the prognosis of MGUS patients by clinical subgroup and risk stratification suggested by Mayo Clinic. Methods: Data is obtained from National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999-2004, a nationally representative health survey with follow-up mortality data updated in December 2011. Subjects who were diagnosed with MGUS were included in the study. They were divided into three groups; IgM MGUS, non-IgM MGUS, and light chain MGUS (LC-MGUS). Median overall survival of three groups was obtained using log-rank test and age-adjusted hazard ratio for death between the groups was obtained using cox-proportional regression model. Finally, we also analyzed median survival and age adjusted hazard ratio on conventional MGUS subjects by Mayo clinic MGUS risk stratification based on risk factors of M-protein&amp;gt;1.5g/dL, non-IgG MGUS, and abnormal free light chain (FLC) ratio. Analyses were performed in R software version 3.2.2, and a P-value &amp;lt;0.05 was considered statistically significant. Results: 22,523 subjects in the cohort were screened for MGUS with serum protein electrophoresis, serum protein immunofixation, serum FLC assay, and M-protein typing. There were 483 subjects with MGUS (47 IgM-MGUS, 385 non-IgM MGUS, and 51 LC-MGUS). The median ages of total MGUS subjects, and subgroups were 70, 72.3, 69 and 73 years old, respectively. Median follow-up was 116 months. Median overall survival was 117 months for IgM MGUS, 173 months for non-IgM MGUS, and 109 months for LC-MGUS (p = 0.03). However, the age adjusted hazard ratio (aHR) did not show significant difference between the sub-groups. Likewise, median overall survival of Mayo Clinic MGUS risk group 0, 1, 2 and 3 was 185 months, 163 months, 137 months, and 76.5 months, respectively (p &amp;lt;0.001). Only high-risk group (risk of 3) showed statistically significant aHR 2.9 (95%CI 1.5∼5.6) compared with low risk group (risk of 0). Conclusion: There was no statistically significant mortality difference between MGUS subgroup. Only high-risk group defined by the Mayo Clinic MGUS risk stratification showed inferior survival and higher risk of death compared to rest of MGUS subjects. Further prospective studies are needed to validate our findings and to investigate whether early interventions for MGUS patients by clinical subgroup and risk stratification are needed rather than the current standard management of watchful-waiting. Citation Format: Hyun-Seok Kim, Jieqi Liu, Brittany L. Gladney, Neil Kothari, Noa Biran, Victor Chang, David S. Siegel. Survival prognosis of MGUS patients by clinical and risk subgroup: a result from a nationally representative prospective cohort. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2639.

Voriconazole Increase the Risk of PN in Multiple Myeloma Patients Treated with Bortezomib-Based Chemotherapy

Background Bortezomib (btz) is the major and potent agent in multiple myeloma (MM) treatment and intravenous (IV) injection is its standard administration route. Our previous study showed that Subcutaneous (SC) administration of btz was an important alternative with comparable efficacy but better safety profile, significantly decreased and delayed the development of peripheral neuropathy (PN) in patients with MM. However, PN still always limited the use of btz. The primary objective is try to identify some correlative factors for PN, then to decrease the risk of PN and the grade of PN.Methods This retrospective study was undertaken at a single centre in China. Patients with NDMM were assigned to receive up to nine 21-day cycles of Btz based regimens, including PAd/VDd/BCd (btz 1.3mg/m2, on days 1, 4, 8 and 11; adriamycin 9mg/m2 intravenously on days 1 - 4; or PLD 30mg/m2, intravenously on days 1, or CTX 500mg/m2, orally on days 1, 8, 15, and dexamethasone 20mg/day, orally or intravenously on days 1, 2, 4, 5, 8, 9, 11 and 12). Btz was administered by SC injection or IV infusion. The basic characteristics, drug combination (especially drugs for fungi), the effect and adverse events were recorded. Then the correlation were analysed.Results 252 (male, n=159) NDMM patients were received Btz based treatment from Oct. 2008 to Nov. 2014. The median age were 56 (26-77). In this group, patients were treated with a median 4 cycles of btz-based chemotherapy. 98, 101 and 53 patients received PAd, BCd and VDd regimen, respectively. 114 patients received IV btz, and 148 received SC btz. The median total Btz dosage was 20.4 (2.6-56.6) mg/m2. Patients achieved at least PR at median 1 (1-7) cycle, and achieved the best response at median 2 (1-9) cycles. The overall response rate (ORR, >=PR) was 95%, with 33.3%, 12.4%, 22.4% achieved CR, nCR and VGPR, respectively. With median follow up 24 months, the median PFS and OS were 28 months, and not arrived, respectively. There was no significant difference between IV and SC group. During their course, 49, 19, 73, and 46 cases received fluconazole, itraconazole, voriconazole, and caspofungin respectively as prophylaxis or treatment for fungi. 140 (55.56%) patients developed PN during their courses, with 17.06% were ≥ grade 3. The median dosage of btz when PN developed was 15.6 mg/m2. In the subgroup which combined voriconazole, 59 (80.82%) patients developed PN, with 39.07% were ≥ grade 3. The median dosage of btz when PN developed was 12.3mg/m2 in this subgroup. In addition, 10 patients (13.70%) developed diarrhea of grade 3/4 and 20 cases (27.4%) developed paralytic ileus of any grade, which may be related to the neuropathy toxicity of btz too. Correlation analysis showed that only voriconazole combination was significantly correlated with PN development (p<0.0001). However, any other factors, including age, sex, the percentage of plasma cells in bone marrow, the level of M-protein, IL-6, TNF-α, β2-MG, ALB, calcium, the type of M-protein, etc, were all without correlation with the development of PN.Conclusions Voriconazole combination significantly increased the risk and the grade of PN in patients treated with btz-based chemotherapy. If this combination can't be avoided, patients should be observed more closely or btz dosage should be decreased earlier. DisclosuresNo relevant conflicts of interest to declare.

Reduced relapse rate in upfront tandem autologous/reduced-intensity allogeneic transplantation in multiple myeloma only results in borderline non-significant prolongation of progression-free but not overall survival

Reduced relapse rate in upfront tandem autologous/reduced-intensity allogeneic transplantation in multiple myeloma only results in borderline non-significant prolongation of progression-free but not overall survival

Carriage of Streptococcus pyogenes in primary school children: M-protein types, pyrogenic toxin genes, and investigation of the clonal relationships between the isolates

M-protein and pyrogenic toxins are the most important virulence factors of Streptococcus pyogenes, and they play significant role in the pathophysiology of acute rheumatoid fever and scarlet fever, respectively. In this study, the pharyngeal carriage of S.pyogenes of the primary school children, clonal relationship of the strains, M-protein types, and the presence of pyrogenic toxin genes were aimed to be investigated. A total of 668 throat cultures obtained from children (age range: 6-16 years) in two primary schools in our region, were included in the study. The clonal relationships of the isolated group A streptococci (GAS) strains were investigated by DiversiLab assay (BioMérieux, France), and the clonal relatedness was confirmed by pulsed-field gel electrophoresis (PFGE) method. M-protein (emm) typing was performed by DNA sequencing as suggested by Centers for Disease Control and Prevention (CDC). The genes encoding pyrogenic toxins, speA and speC, were investigated by an in-house multiplex polymerase chain reaction (PCR) method. S.pyogenes was isolated from 134 (20.05%) of the throat samples. The GAS carriage rate of the students aged ≥10 was statistically higher than those 7-9 years age group (%22 vs %16.4, p<0.05). The M protein gene could be characterized only among 123 isolates by DNA sequencing, and 20 different emm types were detected. The most frequent emm type was emm1 (n=38, 30.9%) followed by emm12 (n=18, 14.6%), emm89 (n=10, 8.1%), emm118 (n=9, 7.3%), and emm4 (n=7, 5.7%). Pyrogenic toxin genes were found in 25 (18.6%) of the isolates, including speA in 11 isolates (8.2%) and speC in 12 isolates (8.9%) and both genes were detected in 2 isolates (1.5%). Sixty-two different Rep (Repetitive extragenic palindromic)-PCR profiles were detected in 134 S.pyogenes isolates by DiversiLab method. Thirteen different clusters were formed by a total of clonally related 36 isolates revealing a strain clustering ratio of 26.9%. Clonal relationship of all isolates in the same cluster was confirmed by PFGE method. In this study, relatively high percentage of GAS carriage was observed among primary school children in our region. The coverage rate of the 30-valent vaccine was determined to be over 90% with respect to M-protein types. Since the pyrogenic toxin-encoding genes were found in one fifth of the isolates from the studied subjects, we concluded that the carrier population may also have high risk for scarlet fever. We also concluded that, the clonal relationship ratio determined among the isolates may be a risk in school transmission of GAS.

Immunoparesis in MGUS - Relationship of uninvolved immunoglobulin pair suppression and polyclonal immunoglobuline levels to MGUS risk categories.

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic, potentially malignant condition. It has been established that annually approximately 1-2% of MGUS cases transforms into one of the malignant forms of monoclonal gammopathies. Progression risk factors include the quantity and type of M-protein, and namely the ratio of free light immunoglobulin chains (FLC). These factors, enable purposeful stratification of MGUS individuals. Some authors consider suppression of polyclonal immunoglobulin levels to be another progression factor. The aim of the study was to compare polyclonal immunoglobulin (PIg) levels with uninvolved heavy/light chain pair (HLC) levels in order to verify the degree of immunoparesis depending on MGUS risk category (0-3). The analyzed set consisted of 159 serum samples from MGUS patients (102 IgG, 57 IgA), who were stratified into 4 risk groups (0 - low, 1 - low-intermediate, 2 - high-intermediate and 3 - high risk of transformation). The results of analysis showed that with increasing degree of MGUS increases risk of immune paresis defined by decreasing levels of polyclonal immunoglobulins, ie. IgA and IgM in the case of IgG MGUS, respectively, IgG and IgM in case of IgA MGUS. Significant differences were also found when analyzing the levels of uninvolved HLC pairs IgG kappa (resp. IgG lambda) in IgG lambda (IgG kappa) dominant secretion. In the case of MGUS with IgA isotype, the results were similar. Discovery of the connection between the degree of immunosuppression and the level of MGUS risk contributes to our understanding of the relationship between biology, development and potential malignant transformation of MGUS. It is apparent that uninvolved HLC pair assay enables more reliable identification of at-risk MGUS patients than asimple quantitative assay for polyclonal immunoglobulins alone.

3-Phosphoinositide-Dependent Protein Kinase 1 (PDPK1) Is a Pivotal Cell Signaling Mediator in Multiple Myeloma

Multiple myeloma (MM) is a highly molecularly heterogeneous hematologic malignancy and remains mostly incurable despite recent improvement of treatment outcome by novel agents. Therefore, the identification of novel and universal targetable therapeutic molecules is a core component for the therapeutic development. Herein, we identified that 3-phosphoinositide-dependent protein kinase 1 (PDPK1), a member of serine threonine kinase, is a rationalistic candidate of a novel therapeutic target against MM. PDPK1 is universally phosphorylated in all eleven MM-derived cell lines examined regardless of type of cytogenetic/genetic abnormalities or the activation/mutation state of FGFR3, RAS, ERK and AKT. PDPK1 promotes the cell proliferation of myeloma cells by activating RSK2Ser227 at N-terminal kinase domain which is a pivotal regulator of molecules that are essential for myelomagenesis, such as c-MYC, IRF4, or Cyclin Ds (Shimura Y, Mol Cancer Ther 2011), and AKTThr308. In contrast, PDPK1 inhibition by a selective inhibitor, BX-912, caused G2/M arrest, which was accompanied by the inactivation of PLK1, and resulted in cell death via induction of apoptosis which was accompanied by the activation of pro-apoptotic BH3-only proteins, BIM and BAD, in myeloma-derived cell lines. These molecular and cytological effects of PDPK1 inhibition in myeloma cells were also validated by gene knockdown by means of RNA interference using two different siRNAs specific for PDPK1. In addition, the cytotoxic effect of BX-912 was not hampered in two cell lines acquiring resistance to bortezomib (BTZ) (Ri M, Leukemia 2010), and PDPK1 inhibition by BX-912 showed additive to synergistic in vitro cytotoxic effects on myeloma cells with melphalan, etoposide, bortezomib or BAY11-7085, an inhibitor for NF-κB. BX-912 also induced cell death in eleven patient-derived primary myeloma cells those were positively isolated by CD138-labelling from bone marrow aspirates, while normal peripheral lymphocytes were significantly less sensitive to PDPK1 inhibitor compared with MM cells. In the clinical setting, PDPK1 was active in myeloma cells of 57 of 65 (87.7%) symptomatic MM patients at diagnosis. While patients backgrounds, such as age, gender, and the type of M-protein, were not significantly different between PDPK1-negative (PDPK1(-)) and PDPK1-positive (PDPK1(+)) patients, patients with the disease stage III according to International Staging System were significantly more frequent in the PDPK1(+) cohort compared with PDPK1(-) cohort. The PDPK1(-) patients tended to exhibit longer overall survival (OS) than the patients with PDPK1(+) (median OS: 2925 days vs. 2155 days, p=0.069) with a median follow-up period of 1310 days (range: 228–3317 days). Of particular, the 8-year OS of PDPK1(-) patients was statistically significantly more favorable than those of PDPK1(+) patients (83% vs. 17%, p=0.041). In addition, when we analyzed the impact of PDPK1 activity on the treatment outcome of patients treated by BTZ and dexamethasone therapy (BD), our results revealed that progression free survival (PFS) of patients with PDPK1(-) was a significantly longer than those of patients with PDPK1(+) (median PFS: PDPK1(-) vs. PDPK1(+), not reached vs. 167 days, p=0.049). The PFS of PDPK1(-) patients treated by high-dose therapy/autologous stem cell transplantation (HDT/ASCT) tended to be longer than those of PDPK1(+) (median PFS: PDPK1(-) vs. PDPK1(+), 972 days vs. 567 days, p=0.125). In conclusion, our study provides the rationale for PDPK1 as a possible universal molecular target for MM with various molecular/cytogenetic features. Especially, PDPK1 is a potential therapeutic target for not only newly diagnosed patients but also patients who are resistant or refractory to currently available anti-myeloma therapies. This study was conducted in accordance with the Declaration of Helsinki and with the approval of the Institutional Review Board. Patient-derived samples were obtained with informed consent. DisclosuresNo relevant conflicts of interest to declare.

Tumor and Renal Response in Patients with Newly Diagnosed Multiple Mieloma and Renal Failure Treated with Bortezomib and Dexamethasone: Results of a Prospective Phase II Trial from Pethema/GEM

Tumor and Renal Response in Patients with Newly Diagnosed Multiple Mieloma and Renal Failure Treated with Bortezomib and Dexamethasone: Results of a Prospective Phase II Trial from Pethema/GEM

Racial disparities in the prevalence of monoclonal gammopathies: a population-based study of 12 482 persons from the National Health and Nutritional Examination Survey

Multiple myeloma (MM) incidence is markedly higher in blacks compared with whites, which may be related to a higher prevalence of monoclonal gammopathy of undetermined significance (MGUS). Our objective was to define the prevalence and risk factors of MGUS in a large cohort representative of the US population. Stored serum samples from the National Health and Nutritional Examination Survey (NHANES) III or NHANES 1999-2004 were available for 12,482 individuals of age ⩾50 years (2331 'blacks', 2475 Hispanics, 7051 'whites' and 625 'others') on which agarose-gel electrophoresis, serum protein immunofixation, serum-free light-chain assay and M-protein typing were performed. MGUS was identified in 365 participants (2.4%). Adjusted prevalence of MGUS was significantly higher (P<0.001) in blacks (3.7%) compared with whites (2.3%) (P=0.001) or Hispanics (1.8%), as were characteristics that posed a greater risk of progression to MM. The adjusted prevalence of MGUS was 3.1% and 2.1% for the North/Midwest versus South/West regions of the United States, respectively (P=0.052). MGUS is significantly more common in blacks, and more often has features associated with higher risk of progression to MM. A strong geographic disparity in the prevalence of MGUS between the North/Midwest versus the South/West regions of the United States was found, which has etiologic implications.

Impact Of Novel Agents To The Additional-Chromosomal Abnormalities In Patients With Multiple Myeloma

ObjectiveIt is well known that myelodysplastic syndrome (MDS) and acute myeloid leukemia(AML) would develop in patients with multiple myeloma. Many of them are considered as therapy-related MDS/AML (t-MDS/AML). Use of novel agents (NAs) such as bortezomib (Bor), thalidomide (Thal), and lenalidomide (Len) has extended survival of patients with multiple myeloma (MM). However, it is concerned whether a long-term treatment with NAs may increase the risk of the t-MDS/AML. So, we explore whether NAs increase the additional-chromosomal abnormalities in patients with multiple myeloma. MethodsSequential 350 patients with MM have been treated at JRCMC from 1998 to 2013. 169 patients have been treated with at least one of the NAs (NAs user); namely Bor was administered to 154 patients, Thal 70, and Len 38. The rest of 181 patients had never been treated with either one of the NAs (NAs non-user). Some patients had additional-chromosomal abnormalities (Ad-CAs) associated with t-MDS/AML by -5/5q-, -7/7q-, der(1;7), +8, 13q-, 20q-, inv(3)/t(3;3), t(11q23), der(12p), 11q-, 16q-, t(3;21), der(1;14). We compared the frequency of Ad-CAs detected by total 1112 bone marrow G-banding findings between NAs users and non-users. ResultsPatients' background is not significantly different between NAs users and non-users in terms of age, sex, M-protein type, and ISS stage. 5 patients showed t-AML and 30 patients revealed t-MDS. Ad-CAs was observed in 13 out of 169 NAs users (7.7%): (Bor 11 cases, Thal 10, and Len 5), while 38 out of 181 NAs non-users (21.0%). A cumulative incidence of appearance of Ad-CAs was significantly higher in non-users (P=0.02). In addition, dose and treatment period of Thal and Len was not different between Ad-CAs-positive and negative patients, but not Melphalan (Mel). -7/7q- was the most frequent Ad-CAs (26.3%) of the 38 cases of Ad-CAs in NAs non-users. In contrast, 13q-, 20q-, and +8 were observed in 10 patients (77%), 6 (46%), and 4 (31%) of the 13 cases of Ad-CAs in NAs users, respectively. DiscussionHigher dose administration of Mel was observed amongst patients who represented Ad-CAs. Treatment progress is represented in the Figure. Upper 13 patients were administered NAs, lower 38 patients were not. The time of Ad-CAs is Point 0 year, before and after treatment years are summarized in the Figure. All the patients who developed t-AML died within 2 years of development. t-MDS/AML which develops in patients with multiple myeloma has a poor prognosis and resistance to treatment. We must select chemotherapy regimen taking into account of the risk of developing t-MDS/AML. [Display omitted] ConclusionThe results of the present study demonstrated no evidence of increased risk of Ad-CAs using NAs including Len was observed. It is suggested that Ad-CAs were associated with therapy strategies that were the previous standard before NAs emerged. However, the possibility of an association between +8,13q-,20q- and the use of NAs cannot be excluded. There were drug lag of the approval of NAs issue in Japan; Bor in 2006, Thal in 2008, Len in 2010. Therefore, longer follow-up periods are necessary for an accurate assessment of the risk. Disclosures:No relevant conflicts of interest to declare.

Codon 72 Polymorphism Of TP53 Gene Is a Novel Prognostic Marker For Thalidomide Therapy In Multiple Myeloma

Backgrounds and purposeRecently, newly developed drugs such as thalidomide, lenalidomide and bortezomib have significantly improved survival of the patients with multiple myeloma (MM). However, certain group of the patients who have characteristic high-risk cytogenetic changes such as deletion of TP53 tumor suppressor gene revealed significantly shorter survival. In patients with deletion of TP53 gene, the somatic point mutation in the residual TP53 gene has been reported to be rare. Thus, the exact role of alteration of TP53 gene in high-risk myeloma remains unclear. Polymorphism of TP53 gene at codon 72 in exon 4, CGC to CCC transition, leads to arginine (Arg) to proline (Pro) amino-acid substitution. Biological analyses showed that the Arg variant more efficiently induces expression of P21 and apoptosis via Ser-6 and 20 phosphorylation of p53 protein. In contrast the Pro variant is less resistant to MDM-2-mediated degradation and more potently induced cell-cycle arrest and DNA damage repair. Recently, clinical significance of this polymorphism has been extensively studied in solid tumors as well as hematological malignancies including non-Hodgkin lymphoma and leukemia. However, consistent association of the polymorphism with cancer risk has not been elucidated.The purpose of this study is to examine codon 72 polymorphism in patients with refractory multiple myeloma (MM) treated with thalidomide, and to elucidate its association with myeloma risk and outcome of thalidomide-therapy. Patients & methodsA total of 37 Japanese patients with refractory or relapsed MM who were treated with thalidomide monotherapy were included in this study. Three cases showed deletion of TP53 gene by fluorescence in situ hybridization (FISH) analyses. The codon 72 polymorphism was evaluated in the rest of 34 patients. Genomic DNA was isolated from bone marrow mononuclear cells. The genomic TP53 gene was amplified by polymerase chain reaction, and the amplified DNAs were directly sequenced. ResultsDirect DNA sequence showed that the Pro/Pro homozygote was observed in six patients (18%), Pro/Arg heterozygote in 12 (35%) and Arg/Arg homozygote in 16 (47%). There was no significant difference in the frequency of the polymorphism between the 34 Japanese MM patients and the healthy Japanese individuals (P=0.44). Thus, association of codon 72 polymorphism with myeloma risk has failed to be elucidated. The response rate to thalidomide therapy was 33% in the patients with Pro/Pro, 27% in Pro/Arg and 44% in Arg/Arg (P=0.49), respectively. Other clinical backgrounds including age, sex, Durie-Salomon stage, ISS stage, serum creatinine, albumin, b2M, calcium, hemoglobin levels and M-protein type were not correlated with TP53 codon 72 polymorphism, either.Progression free survival (PFS), overall survival (OS) and post-relapse survival were shown in Figure 1. The patients with Pro allele tended to show shorter PFS; 5 weeks for the patients with Pro/Pro versus 32 weeks for those with Pro/Arg plus Arg/Arg (P=0.07) (Figure 1). Overall survival (OS) of the patients with Pro/Pro, Pro/Arg and Arg/Arg allele was 18 weeks, 49 weeks and 133 weeks, respectively (P=0.027). Especially, the patients with Pro/Pro allele revealed significantly shorter OS compared with those with Pro/Arg plus Arg/Arg (18 weeks versus 100 weeks, P=0.023) (Figure 1). Significant difference of OS in patients with Pro/Pro+Pro/Arg vs Arg/Arg (P= 0.032) suggested the dominant effect of Pro allele for poorer prognosis. Post-relapse survival of the patients with Pro/Pro, Pro/Arg and Arg/Arg allele was 11, 42 and 64 weeks, respectively (P=0.054). Post-relapse survival for Pro/Pro versus Pro/Arg plus Arg/Arg were 11 weeks versus 64 weeks (P=0.029). ConclusionThese results indicated that codon 72 polymorphism did not correlated with myeloma risk, but significantly associated with therapeutic outcome. Namely, the patients with Pro allele revealed earlier relapse and shorter post-relapse survival, resulted in shorter OS in thalidomide therapy. Further evaluation is needed to clarify whether the codon 72 polymorphism will be a new prognostic marker for the treatment with novel drugs. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Multiple Myeloma Patients With Prior Knowledge Of MGUS Have a Better Survival Compared To Multiple Myeloma Patients Without Prior Knowledge Of MGUS

BackgroundA recent prospective cancer screening trial including over 77,000 individuals followed-up for over 10 years shows that multiple myeloma (MM) is consistently preceded by a precursor state, monoclonal gammopathy of undetermined significance (MGUS). Clinically, most newly diagnosed MM patients are unaware of their prior MGUS state. Importantly, among individuals diagnosed with MGUS, only a small proportion will develop MM or a related malignancy during their lifespan. Current clinical guidelines suggest lifelong, annual monitoring of individuals diagnosed with MGUSto detect progression to MM or related disorders. At this time, the impact of annual monitoring on the outcome of patients who eventually develop MM is unknown. In addition, as MGUS is usually diagnosed during work-up for another disorder, the impact of comorbidity in MM patients with prior knowledge of MGUS is unknown. We assessed the impact of prior knowledge of MGUS in relation to MM survival. Patients and MethodsThe study cohort consisted of 14,798 individuals diagnosed with MM in Sweden 1976-2005, with follow-up until 2007. A total of 394 patients had previously been diagnosed with MGUS. Patients diagnosed with MM were identified through the Swedish Cancer Register. MM patients with prior knowledge of MGUS were identified from a nationwide MGUS cohort which was established from in and out-patient units from major hospital-based hematology/oncology centers in Sweden. Details of sex, date of birth, date of diagnosis, type and concentration of M-protein at MGUS diagnosis, and comorbidities (autoimmune diseases, infections, other malignant diseases, ischemic heart diseases, heart failure, cerebrovascular diseases, chronic lung diseases and renal diseases) were gathered for all patients. Survival rate from time of MM diagnosis comparing patients with and without prior knowledge of MGUS was calculated with a Kaplan Meier method. Risk factors for death were analysed in a Cox proportional hazards model where relative risks (RR) and 95% confidence intervals (CIs) were calculated. A Chi-square test was used to evaluate whether there was a significant difference in comorbidities. ResultsMM patients with prior knowledge of MGUS had significantly (RR = 0.86; CI = 0.77-0.96) better survival (median = 2.8 years; 95% CI = 2.6-3.3) than MM patients without prior knowledge of MGUS (median = 2.1 years; 95% CI = 2.1-2.2; Figure). Older age at diagnosis (RR = 1.04; 95% CI = 1.04-1.05) was associated with an inferior survival, whereas female sex and recent year at diagnosis were related to improved survival: RR = 0.86 (CI = 0.83-0.89) and 0.95 (CI = 0.95-0.95), respectively. There was no difference in survival comparing MGUS patients with high (>1.5 g/dL) versus low (<1.5 g/dL) M-protein concentration (RR = 1.01; 95% CI 0.72-1.41). Unexpectedly, M-protein concentration ≤0.5 g/dL at MGUS diagnosis was associated with poored survival than M-protein concentration greater than 0.5 g/dL (RR = 1.86; 95% CI = 1.13-3.04, p=0.014). [Display omitted] Autoimmune diseases (p<0.001), infections (p<0.001), other malignant diseases (p<0.001), ischemic heart diseases (p<0.001), heart failure (p<0.001), cerebrovascular diseases (p<0.001), and renal diseases (p<0.001) at diagnosis of MM were significantly more common in MM patients with prior knowledge of MGUS than in MM patients without. ConclusionsBased almost 15,000 MM patients diagnosed in Sweden between 1976 and 2005, for the first time, we found that prior knowledge of MGUS is associated with better survival (median overall survival 2.8 versus 2.1 years). Given patterns of co-morbidities, the observed survival difference is likely a reflection of the fact that MGUS patients are evaluated more often for signs of MM progression and may be diagnosed/treated at an earlier stage. The finding that low-risk MGUS patients that develop MM had a shorter survival rate is interesting and may be due to less intense monitoring and needs to be studied further. Our observations raise the question whether screening for MGUS, e.g., above the age of 50, could translate into earlier detection/treatment of MM (“early myeloma“) and lead to better survival. Future prospective studies are needed to explore these findings further. Disclosures:Turesson:Celgene Corp: Honoraria.

Maintenance Therapy After Stem-Cell Transplantation for Multiple Myeloma with Bortezomib/Thalidomide Vs. Thalidomide Vs. alfa2b-Interferon: Final Results of a Phase III Pethema/GEM Randomized Trial

AbstractAbstract 334 Introduction:The Spanish Myeloma Group (PETHEMA/GEM) conducted a randomized phase III trial comparing induction with thalidomide/dexamethasone (TD) vs. bortezomib/thalidomide/dexamethasone (VTD) vs. VBMCP/VBAD/Bortezomib (VBMCP/VBAD/B) in patients 65 years-old or younger with newly diagnosed symptomatic MM and ASCT with MEL-200 followed by maintenance with thalidomide/bortezomib (TV) vs. thalidomide (T) vs. alfa-2b-interferon (alfa2-IFN). The induction part of the study has been recently published and the maintenance results are reported here. End-points:The primary end-point was progression-free survival (PFS) and the secondary end-points were increase of response rate, overall survival (OS) and safety. Patients and Methods:The maintenance treatment consisted of TV (thalidomide 100 mg daily plus one cycle of bortezomib at 1.3 mg/m2 on days 1, 4, 8 and 11 every 3 months) versus T (single agent thalidomide at a dose of 100 mg daily) versus alfa2-IFN (subcutaneous alfa2b-IFN at a dose of 3 MU three times per week). The planned maintenance duration was three years or until disease progression or toxicity. From February 1, 2007 to January 27, 2011 266 patients were randomized to maintenance therapy (TV: 89; T: 87, alfa2-IFN: 90). Response and survival were evaluated on an intention-to-treat basis. Responses, relapses and progressions (EBMT criteria) were monitored by an external contract research organization and centrally reassessed. Results:Patient's characteristics at diagnosis such as age, M-protein type, ISS stage, cytogenetics and presence of extramedullary plasmacytomas as well as induction regimen (VTD, TD and VBMCP/VBAD/Bortezomib) and diagnosis-randomization interval were similarly distributed among the 3 arms. The response status at the time of randomization for maintenance after ASCT was CR: 51%, nCR: 12%, PR: 34%, MR 2% and SD: 1% and was well balanced in the three groups. The CR rate with maintenance was improved by 19% with TV, 15% with T and 17% with alfa2-IFN (p=NS). After a median follow-up of 34.9 months, the PFS was significantly longer with TV compared with T and alfa2-IFN (figure 1, p=0.0009). However, OS was not significantly different among the 3 arms. Grade 3 and 4 hematological toxicity was similar (22.2% vs. 16% vs. 21.8%). No peripheral neuropathy (PN) was observed with alfa2-IFN being its frequency similar with TV (12.2%) and T (10.1%). No grade IV PN was observed. Dose reductions for TV, T and alfa2-IFN were required in 33.3%, 33.7% and 19.5% of the patients, respectively. The discontinuation rate due to progressions was not significantly diferent among the three arms (35% vs 24% vs 20%, p=NS). The discontinuation rate due to toxicity was higher with thalidomide compared with TV (30.3% vs. 15.6%, p= 0.08) and with alfa2-IFN (30.3% vs. 18.3%, p=0.17). Patients with high-risk cytogenetics [t(4;14), t(14;16) and/or del 17p] had a trend towards a shorter PFS (p=0.1) and a significantly shorter OS (p=0.03). The incorporation of bortezomib was not able to overcome the poor impact of high-risk cytogenetics. Conclusion:The addition of bortezomib to thalidomide maintenance resulted in a significantly longer PFS when compared with thalidomide alone or with single agent alfa2-IFN with no increased toxicity. However, the addition of bortezomib did not overcome the poor impact of high-risk cytogenetics. [Display omitted] Disclosures:Rosiñol:Janssen, Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Oriol:Janssen: Honoraria; Celgene: Honoraria. De La Rubia:Celgene, Janssen: Consultancy, Speakers Bureau. Granell:Janssen: Honoraria; Celgene: Honoraria. de Arriba:Jansen: Honoraria; Celgene: Honoraria. Alegre:Janssen: Honoraria; Celgene: Honoraria. Cibeira:Janssen: Honoraria; Celgene: Honoraria. Mateos:Janssen: Honoraria; Celgene: Honoraria. Lahuerta:Janssen: Honoraria; Celgene: Honoraria. San Miguel:Janssen: Honoraria; Celgene: Honoraria; Onix: Honoraria; Novartis: Honoraria. Bladé:Janssen: Honoraria; Celgene: Honoraria; Novartis: Honoraria.

Similar Efficacy of Thalidomide-Based and Bortezomib-Based Regimens In the First Relapse of 209 Multiple Myeloma Patients Previously Untreated with Novel Drugs

AbstractAbstract 5027 Background:Novel agents, such as immunomodulatory drugs and proteasome inhibitors, have substantially changed the treatment paradigm of multiple myeloma (MM). Until now, many combination regimens with novel drugs have been published, but different regimens have rarely been compared in the treatment of the first relapse of MM. Aims:In this report, we describe the outcome of a cohort of 209 patients (pts) with the first relapse of MM treated with thalidomide-based and bortezomib-based regimens with aims to compare the efficacy of these therapies. Methods:Eighty-two percent of pts (171/209) had stage III according to Durie-Salmon (DS), 17% (35/209) II and 1% (3/209) I, clinical stages according to International Staging System (ISS) were the following: stage 1 in 46% of pts (92/199), stage 2 in 29% of pts (57/199) and stage 3 in 25% of pts (50/199). Renal insufficiency was presented in 14% of pts (30/209). Median age was 64 years (range: 34–84). Thalidomide-based (T) regimens were used in 105 pts; thalidomide + alkylating agent + dexamethasone: 91 cases (87%), thalidomide + dexamethasone: 5 cases (5%), alone thalidomide: 9 cases (8%). The daily dose of thalidomide was 100–200 mg. Bortezomib-based (B) regimens were used in 106 pts; bortezomib + alkylating agent + dexamethasone: 58 cases (55%), bortezomib+alkylating agent or dexamethasone: 40 cases (38%), alone bortezomib: 8 cases (7%). Bortezomib was used in standard dose 1.3 mg/m2 intravenously on days 1, 4, 8, 15. The cycle repeated on day 21–28 for up to 8 cycles or until progression. Median of T and B treament cycles was 5, range 1–8. No statistically significant differences were observed between the T and B groups in baseline clinical parameters including age, clinical stages according to ISS and DS staging systems, the type of M-protein and presence of renal impairment. The first-line therapy was comparable for both T and B groups and it is not include novel agents. Median follow-up from start of treatment was 19.5 months (range 0.9–53.3). Results:In T group, overall response rate (ORR) was 51% (51/100), 11% of pts (11/100) achieved the complete response (CR), 16% of pts (16/100) were in very good partial response (VGPR), 24% of pts (24/100) in partial response (PR), 9% of pts (9/100) had minimal response (MR) or stable disease (SD) and 40% of pts (40/100) had progression of disease. Median time to progression (TTP) from the start of relapse treatment was 13.1 months, median overall survival (OS) was 30.4 months. Patients in T group with ORR had significantly longer OS than pts without ORR (median 46.1 months versus 22.1 months; p = 0.005). Clinical stages according to ISS in T group significantly influenced both TTP (p = 0.004) and OS (p = 0.001).In B group, ORR was 50% (34/68), 9% of pts (6/68) were in CR, 16% of pts (11/68) were in VGPR, 25% of pts (17/68) in PR, 17% of pts (12/68) had MR or SD and 32% of pts (22/68) had progression of disease. Median TTP from start of relapse treatment was 16.7 months, median OS was 37.2 months. Patients in B group with ORR had significantly longer OS than pts without ORR (median 50.1 months versus 21.2 months; p = 0.002). Clinical stages according to ISS in B group did not significantly influence TTP (p = 0.483) and OS (p = 0.207).Age, renal impairment and type of M-protein did not significantly affect TTP and OS in both T and B groups. Conclusion:The thalidomide-based and bortezomib-based regimens are similarly effective in treatment of the first relapse MM with ORR 50–51%. No statistically significance differences were observed between thalidomide-based and bortezomib-based regimens in terms of TTP (p = 0.207) and OS from the start of relapse treatment (p = 0.889). Disclosures:No relevant conflicts of interest to declare.