Lenalidomide-based Regimens Research Articles

Carfilzomib-Lenalidomide-Dexamethasone in the Management of Lenalidomide-Refractory Multiple Myeloma

Background Carfilzomib is an epoxyketone proteasome inhibitor of second generation, proved to be effective and safe in relapsed and refractory Multiple Myeloma (rrMM), in combination with dexamethasone or lenalidomide and dexamethasone. Aims In this retrospective observational trial, it has been evaluated efficacy and safety of carfilzomib, in combination with lenalidomide-dexamethasone (KRD) as salvage regimen in patients with rrMM, refractory to lenalidomide, where lenalidomide-based regimens have no proven efficacy. Methods 41 patients (23 M/18 F), with rrMM, median age at diagnosis 63.7 years (r. 43-82), median age at start of treatment 67 years (r. 48-84) previously treated with several lines of treatments (median 3, r. 2-11), underwent to KRD regimen (ASPIRE trial schedule) for a median treatment cycles of 8 (r 2-18). ISS was equally distributed, and all patients had previously been treated with bortezomib and IMIDs, and were refractory to this agents. 61% (19/31) of them had undergone at least to a single ASCT. Results According to IMWG criteria, after a median follow-up of 9 months (r. 2-18), ORR was 68,2% (28/41: 9 CR, 12 VGPR, 7 PR) with 5 progressive diseases (PD) and 8 patients in stable disease (SD): this can be considered as an impressive result in this subset of rrMM patients, refractory to lenalidomide. In particular, for 11 patients, KRD was, after having achieved at least a PR, a bridge to second/third autologous SCT. Median time to response was 1.3 months (r.1-4), median OS from diagnosis was 62 months (r. 9-170), median OS from start of Carfilzomib was 11 months (r. 2-18). Carfilzomib was well tolerated, with grade 2 anemia in 39%(16/41) of patients, successfully managed by ESAs, without necessity of blood transfusions; 29% (12/41) grade 3-4 neutropenia (pegfilgrastim in primary prophylaxis was given, no ospedalization was required, no septic shocks were observed); 34% (14/41) grade 2, 21% (9/41) grade 3 and 12% (5/41) grade 4 thrombocytopenia, without hemorrhagic events and transfusion-dependency. Moreover, it was observed pneumonia in 39% (16/41) of patients, treated by common antibiotic drugs and always solved. A cardiac monitoring was performed for all patients: hypertension (grade 2-3) in 34% (14/41) of patients; fatigue in 39% (16/31) of patients. Conclusions Carfilzomib-Lenalidomide-Dexamethasone has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, also lenalidomide, and it could be considered as a bridge to a second autologous or allogenic SCT. Disclosures Lucchesi: Incyte: Honoraria; Novartis: Honoraria; Pfizer: Honoraria. Martinelli:Amgen: Consultancy; Celgene: Consultancy, Speakers Bureau; Jazz: Consultancy; Incyte: Consultancy; Pfizer: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy; Daichii Sankyo: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Janssen: Consultancy.

Daratumumab with Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma and Severe Renal Impairment: Results on Efficacy and Safety of the Phase 2 Dare Study

Daratumumab with Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma and Severe Renal Impairment: Results on Efficacy and Safety of the Phase 2 Dare Study

Treatment Patterns and Healthcare Resource Utilization in Patients with Multiple Myeloma and Baseline Renal Impairment

Background: Renal impairment (RI) is associated with substantial clinical and economic burden in patients with multiple myeloma (MM), but real-world data reporting on healthcare resource utilization (HRU) and outcomes in these patients are lacking. We assessed treatment patterns, overall survival (OS), HRU and associated costs across lines of therapy (LoT) in patients with MM who had baseline RI. Methods: We identified patients (aged ≥18 years) with continuous Part A, B and D coverage who initiated pharmacologic therapy for MM between January 1, 2012 and December 31, 2016. Baseline demographics, disease characteristics, and treatment patterns from first-line to fourth-line (1L-4L) were reported for all eligible patients (main cohort). Within this cohort, a subgroup of patients diagnosed with RI at baseline (RI subgroup) were identified using appropriate International Classification of Diseases (ICD)-9 and ICD-10 codes. Treatment regimens were identified during the first 60 days following start of each LoT; stem cell transplantation (SCT) in 1L was considered part of the 1L regimen. The end of each LoT was indicated by treatment augmentation, treatment switching (after >60 days), discontinuation of all agents (for >90 days), or death. Overall survival (Kaplan-Meier analysis) was defined as time from start of each LoT until death or censoring (end of data/Medicare coverage). All-cause HRU categories were identified during each LoT and reported as incidence rate per patient per month (PPPM); associated all-cause healthcare costs during LoT were reported in 2017 US$. Results are presented using standard descriptive statistics. Results: A main cohort of 10,026 patients was identified; of these, a RI subgroup of 714 patients with baseline RI was identified (7.1% of main cohort). At 1L initiation, the RI subgroup was generally younger (71.9 vs. 74.6 years), had a lower proportion of females (47.8% vs. 53.1%) and had a higher proportion of Medicare coverage for end-stage renal disease (62.9% vs. 6.3%) than the main cohort. Patients with RI had a higher mean Charlson Comorbidity Index score (excluding MM; 4.8 vs. 3.3) and a higher proportion of patients with comorbidities (anemia: 72.5% vs. 57.9%; diabetes with chronic complications: 38.7% vs. 27.1%; cardiovascular diseases: 97.2% vs. 82.5%) than the main cohort. In the RI subgroup, among patients who received SCT in 1L (n=76), bortezomib-dexamethasone (Vd) was the most frequent 1L regimen (39.5%), followed by bortezomib-lenalidomide-dexamethasone (VRd; 17.1%) and bortezomib-cyclophosphamide-dexamethasone (VCd; 15.8%). In patients who had no SCT in 1L, Vd was the most frequent 1L regimen (59.5%), followed by VCd (12.7%) and lenalidomide-dexamethasone (Rd; 12.1%). Among patients in the RI subgroup who progressed to 2L therapy, 61.7% received lenalidomide-based regimens in 1L. Newer MM therapies such as carfilzomib, pomalidomide, ixazomib, daratumumab, and elotuzumab were used more frequently in later LoTs (2L: 25.6%; 3L: 50.0%; 4L: 68.8%). Median OS from start of 1L was shorter in the RI subgroup than in the main cohort (29.9 vs. 46.5 months; Table), and this difference was consistent across each subsequent LoT. Incidence of HRU during 1L (Table) was generally higher in the RI subgroup than the main cohort, particularly for inpatient days (1.3 vs. 0.7 PPPM) and home health services (0.9 vs. 0.5 PPPM); this pattern was consistent between cohorts across each subsequent LoT. Total costs in the 1L RI subgroup vs. main cohort (Table) were $14,782 vs. $12,451; the cost differential was maintained across each subsequent LoT. The key driver of this difference was the additional medical service costs ($12,047 vs. $7,459 in 1L) incurred by patients with RI. Conclusion: Patients with MM who had baseline RI were shown to experience higher clinical and economic burden in real-world clinical practice than the overall MM population. This burden was maintained across LoTs. Efficacious regimens that help improve renal function with minimal toxicity would enable patients with MM and RI to persist with treatment and may help address unmet need in this subgroup of patients. Table Disclosures Hari: BMS: Consultancy; GSK: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Takeda: Consultancy; Incyte Corporation: Consultancy. Araujo:Sanofi Genzyme: Current Employment. Latremouille-Viau:Sanofi Genzyme: Consultancy, Other: Dominique Latremouille-Viau is an employee of Analysis Group, Inc. which received consultancy fees from Sanofi Genzyme.; Novartis Pharmaceutical Corporation: Consultancy, Other: Dominique Latremouille-Viau is an employee of Analysis Group, Inc. which received consultancy fees from Novartis.. Lin:Sanofi Genzyme: Current Employment. Davidson:Sanofi Genzyme: Other: Mikhail Davidson is an employee of Analysis Group, Inc which received consultancy fees from Sanofi Genzyme.. Guerin:Sanofi Genzyme: Consultancy, Other: Annie Guerin is an employee of Analysis Group, Inc. which received consultancy fees from Sanofi Genzyme.; Abbvie: Consultancy, Other; Novartis Pharmaceuticals Corporation: Consultancy, Other: Annie Guerin is an employee of Analysis Group, Inc. which received consultancy fees from Novartis.. Sasane:Sanofi Genzyme: Current Employment.

MM-385: Carfilzomib-Lenalidomide-Dexamethasone in the Management of Lenalidomide-Refractory Multiple Myeloma

Background Carfilzomib is an epoxyketone proteasome inhibitor of second generation, proved to be effective and safe in relapsed and refractory Multiple Myeloma (rrMM), in combination with dexamethasone or lenalidomide and dexamethasone. Aims In this retrospective observational trial, it has been evaluated efficacy and safety of carfilzomib, in combination with lenalidomide-dexamethasone (KRD) as salvage regimen in patients with rrMM, refractory to lenalidomide, where lenalidomide-based regimens have no proven efficacy. Methods 41 patients (23 M/18 F), with rrMM, median age at diagnosis 63.7 years (r. 43-82), median age at start of treatment 67 years (r. 48-84) previously treated with several lines of treatments (median 3, r. 2-11), underwent to KRD regimen (ASPIRE trial schedule) for a median treatment cycles of 8 (r 2-18). ISS was equally distributed, and all patients had previously been treated with bortezomib and IMIDs, and were refractory to this agents. 61% (19/31) of them had undergone at least to a single ASCT. Results According to IMWG criteria, after a median follow-up of 9 months (r. 2-18), ORR was 68,2% (28/41: 9 CR, 12 VGPR, 7 PR) with 5 progressive diseases (PD) and 8 patients in stable disease (SD): this can be considered as an impressive result in this subset of rrMM patients, refractory to lenalidomide. In particular, for 11 patients, KRD was, after having achieved at least a PR, a bridge to second/third autologous SCT. Median time to response was 1.3 months (r.1-4), median OS from diagnosis was 62 months (r. 9-170), median OS from start of Carfilzomib was 11 months (r. 2-18). Carfilzomib was well tolerated, with grade 2 anemia in 39%(16/41) of patients, successfully managed by ESAs, without necessity of blood transfusions; 29% (12/41) grade 3-4 neutropenia (pegfilgrastim in primary prophylaxis was given, no ospedalization was required, no septic shocks were observed); 34% (14/41) grade 2, 21% (9/41) grade 3 and 12% (5/41) grade 4 thrombocytopenia, without hemorrhagic events and transfusion-dependency. Moreover, it was observed pneumonia in 39% (16/41) of patients, treated by common antibiotic drugs and always solved. A cardiac monitoring was performed for all patients: hypertension (grade 2-3) in 34% (14/41) of patients; fatigue in 39% (16/31) of patients. Conclusions Carfilzomib-Lenalidomide-Dexamethasone has shown significant efficacy in a particularly severe setting of patients, relapsed and refractory to all available therapeutic resources, also lenalidomide, and it could be considered as a bridge to a second autologous or allogenic SCT. Disclosures Lucchesi: Incyte: Honoraria; Novartis: Honoraria; Pfizer: Honoraria. Martinelli: Amgen: Consultancy; Celgene: Consultancy, Speakers Bureau; Jazz: Consultancy; Incyte: Consultancy; Pfizer: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy; Daichii Sankyo: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Janssen: Consultancy.

Venous thromboembolism risk with contemporary lenalidomide-based regimens despite thromboprophylaxis in multiple myeloma: A systematic review and meta-analysis.

Thromboprophylaxis is routinely used with lenalidomide-based regimens in multiple myeloma because of a substantial risk of venous thromboembolism (VTE). However, little is known about the incidence of VTE with contemporary lenalidomide-based regimens. The objective of the current study was to estimate the incidence of VTE despite thromboprophylaxis with currently used lenalidomide-based regimens in patients with myeloma. The Ovid MEDLINE, Embase, and Cochrane databases were queried from study inception to January 2019 for keywords to cover the following concepts: "lenalidomide," "venous thromboembolism," and "multiple myeloma." Phase 1, 2, and 3 clinical trials evaluating lenalidomide-based regimens with thromboprophylaxis were included. The pooled incidence rate of VTE was estimated using a random-effects model. The search generated 1372 citations, with 51 clinical trials and 9069 patients included for analysis. The most common thromboprophylaxis agents were aspirin, low-molecular-weight heparin or warfarin, administered either per risk-stratification or at investigators' discretion. The pooled incidence of VTE in trials of patients who had newly diagnosed and relapsed/refractory myeloma was 6.2% (95% CI, 5.4%-7.1%) over median treatment durations ranging from 2 to 34 cycles, which translated into 1.2 VTE events per 100 patient-cycles (95% CI, 0.9-1.7 VTE events per 100 patient-cycles). Among contemporary regimens, the risk of VTE was low with combined lenalidomide and low-dose dexamethasone (0.2 [95% CI, 0.1-0.6] events/100 patient-cycles) and lenalidomide maintenance (0.0 [95% CI, 0.0-0.7] events per 100 patient-cycles). VTE risk was higher with combined lenalidomide and low-dose dexamethasone plus proteasome inhibitors (1.3 [95% CI, 0.7-2.3] events per 100 patient-cycles). Despite adequate thromboprophylaxis, lenalidomide-based regimens have a substantial risk of VTE in controlled clinical trial settings. Further studies are needed on new thromboprophylaxis strategies with regimens that have a high VTE risk.

Cereblon (CRBN) gene polymorphisms predict clinical response and progression-free survival in relapsed/refractory multiple myeloma patients treated with lenalidomide: a pharmacogenetic study from the IMMEnSE consortium

Cereblon (CRBN) is crucial for antiproliferative and immunomodulatory properties of immunomodulatory drugs. The objective of this study was to verify whether germline single nucleotide polymorphisms (SNPs) in the CRBN gene may influence response to lenalidomide in multiple myeloma (MM). Fourteen tagging SNPs covering the genetic variability in the CRBN gene region were genotyped in 167 Polish patients with refractory/relapsed MM treated with lenalidomide-based regimens. We found that carriers of minor alleles of two studied CRBN SNPs rs1714327G > C (OR = 0.26; 95% CI = 0.1–0.67; p = .0055, Bonferroni corrected p = .033) and rs1705814T > C (OR = 0.22; 95% CI = 0.07–0.65; p = .0063, Bonferroni corrected p = .037) were significantly associated with lower probability of achievement at least partial remission while treated with lenalidomide-based regimens, using the dominant inheritance model. Moreover, one of these SNPs, namely rs1705814T > C, was correlated with shorter progression-free survival (HR = 2.49; 95%CI = 1.31–4.74, p = .0054, Bonferroni corrected p = .033). It is suggested that selected germline CRBN allelic variants (rs1714327G > C and rs1705814T > C) affect lenalidomide efficacy in patients with relapsed/refractory MM.

Treatment with Novel Agents in Patients with Multiple Myeloma in México: Data of Characteristics, Treatment Patterns and Outcomes from a Health Care System

Introduction: In the last decade, multiple myeloma (MM) therapy has changed due to management strategies including proteasome inhibitors and immunomodulatory drugs. However, in México these drugs are not affordable for every health care system so there is little data regarding treatment with these agents and their outcomes. Methods: We retrospectively reviewed the clinical records of patients diagnosed with MM from January 2004 to June 2018, at different hospitals from the Petróleos Mexicanos healthcare services in México. Diagnosis and treatment response were defined according to the International Myeloma Working Group (IMWG) criteria. Baseline and follow-up characteristics and dates of progression, recurrence, death or last follow up were recollected. Overall survival (OS) was calculated from the date of diagnosis to the date of death from any cause or last follow-up. Event free survival (EFS) was defined from date of diagnosis to the time of progression, relapse or death from any cause or loss of follow-up. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Risk factors related to EFS and OS were identified through univariate and multivariate analysis by means of Cox proportional Hazard regression model. Results: A total of 145 patients with MM were included. Median age at diagnosis was 66 years (range 33-94); 38% were female. The most frequent serum monoclonal protein type was IgG. At the time of presentation, 9% of patients had hypercalcemia; 30% renal insufficiency; 83% had anemia < 10 g/dL; 81% osteolytic lesions and 30% had bone marrow plasma cell percentage ≥60%. ISS stages I, II and III were present in 20%, 27% and 53% of cases. 60% of patients received bortezomib-based induction treatment. Only 6% were treated using the combination of bortezomib and lenalidomide plus steroid, and 2% with lenalidomide plus dexamethasone as first line induction regimen. The rest of the cohort received treatment using melphalan, thalidomide or anthracycline-based chemotherapy. The median follow-up was 47 months (range 2-182). Median OS for the entire cohort was 56 months (95% confidence interval [CI] 42.3-69.7). Six patients (4%) died within six months of diagnosis from renal failure and infections attributed to the disease. 106 patients had evaluable response according to IMWG criteria. Overall response rate was 76% (Complete response 26%; very good partial response (VGPR) 38%; partial response 29%). Only 21 (14%) patients underwent autologous stem-cell transplantation (ASCT). All cases received novel agents as first line regimen and achieved VGPR or better before the procedure. 53 (50%) relapsed during follow up. 38% received second line treatment with lenalidomide-based regimens and 11% were treated with carfilzomib, immunomodulatory drug and steroid combination. Median OS was 56 months (95% Confidence Interval [CI], 42.3- 69.7). Patients older than 65 years had worse OS (31 months; 95% CI, 19.7-42.3) compared to younger patients (53 months; 95% CI, 25.3-60.7; P= 0.001) as well as those with advanced Durie- Salmon stage or ISS score. Treatment with novel agents had no impact in OS in comparison to other regimens (median 75 months vs 44 months, P = 0.21). On the other hand, in those who received ASCT as consolidation, OS was 130 months compared to 61 months in the group treated with chemotherapy alone. On univariate and multivariate analysis, we identified age > 65 years (hazard ratio [HR] 2.6; 95% IC 1.45- 4.7; P = 0.01) and ASCT (HR 0.3; 95% IC 0.12- 0.77; P = 0.012) as statistically significant factors for survival. Median EFS was 30 months (95% CI, 20.7- 39.9). We observed a trend towards a better EFS in patients treated using bortezomib and/or lenalidomide-base regimens (36 months; 95% CI, 21.5- 50.5) compared to those who received other treatment strategies (26 months; 95% CI, 13.4-38.6; P = 0.093). Univariate analysis identified age > 65 years (HR 2.1; 95% IC 1.36- 3.42; P = 0.01) as a significant factor for worst EFS; and VGPR or better (HR 0.54; 95% IC 0.45- 0.65; P = 0.001) as well as ASCT (HR 0.34; 95% IC 0.175- 0.67; P = 0.002) as factors associated to better outcomes. Only age and ASCT remained as independent prognostic factors on multivariate analysis. Conclusion: Outcomes on this study are similar to the reported by other series in México and Latin America. These findings reinforce the need to expand and improve access to better treatments and health coverage in México. Figure Disclosures No relevant conflicts of interest to declare.

Efficacy of Daratumumab with Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma and Severe Renal Impairment: An Interim Analysis of a Phase 2 Study (the DARE Study)

Efficacy of Daratumumab with Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma and Severe Renal Impairment: An Interim Analysis of a Phase 2 Study (the DARE Study)

Systematic Literature Review on Global Real-World Treatment Patterns of Mantle Cell Lymphoma (MCL)

Introduction: MCL is an aggressive type of non-Hodgkin's lymphoma, and was reported associated with early relapse and poor long-term survival. Treatment options include chemotherapy, immunotherapy, and molecular targeted therapies. As of 2019, molecular targeted therapies available in the United States indicated for the treatment of MCL include the proteasome inhibitor bortezomib, the immunomodulatory drug lenalidomide (following two previous lines of therapy), and the Burton's tyrosine kinase inhibitors (BTKIs) ibrutinib and acalabrutinib (following at least one previous line of therapy). Objective/Methods: To examine the real-world treatment patterns of patients with MCL globally, a systematic literature review was performed (2010-2019) with predefined methodology and inclusion and exclusion criteria. Embase and Medline were searched via ProQuest and the Cochrane Controlled Register of Trials (CENTRAL) via the Cochrane Library. Results: Of the 2207 publications identified, 6 publications (US, n = 4; EU, n = 2) provided information on the first-line treatment of MCL (Table). The most commonly administered first-line treatments were bendamustine-rituximab; high dose cytarabine ± rituximab; and cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (CHOP) ± rituximab although differences were noted across studies. Most patients received rituximab first-line either in combination with chemotherapy (54.2%-87.5%) or as monotherapy (12.9%-28.9%); although in some studies, rituximab maintenance therapy could not be excluded. The most commonly administered second-line therapies were cytarabine, rituximab monotherapy, and ibrutinib while third-line therapies were rituximab monotherapy, ibrutinib, and temsirolimus. Nine studies provided data on the real-world treatment of MCL with the BTKI ibrutinib (EU, n = 3; US, n = 5; EU/US, n = 1; Table); no real-world studies were identified for acalabrutinib. Six studies enrolled patients only with relapsed or remitting MCL; 3 studies enrolled patients (≤7.5%) who received ibrutinib as first-line therapy. Ibrutinib second-line therapy was administered to 13%-20% of patients and third-line therapy to 21% of patients. Ibrutinib discontinuation rates in 7 studies varied from 38.7%-83.6%. Non-response, including relapse or progression (34.6%-100%), was the main cause of discontinuation, followed by toxicity/adverse events (8.1%-25.6%). Across studies, toxicity/adverse events causing ibrutinib discontinuation included atrial fibrillation, bleeding/hemorrhage, chronic obstructive pulmonary disease, diarrhea, herpes zoster, infection, leukocytosis/ lymphocytosis, lung cancer, myelodysplastic syndrome, and thrombocytopenia. Two studies provided information on ibrutinib dose reductions (16.4% of patients) and ibrutinib dose interruptions (7.8%-30.2% of patients). Treatment options administered post-ibrutinib included rituximab (52.7%), hyper-CVAD + rituximab (16.7%-25.8%), lenalidomide-based regimens (9.7%-41.5%), and bortezomib-based regimens (8.4%-34.4%). Conclusion: Our analyses showed that most patients with MCL received first-line chemoimmunotherapy, although regimens varied across studies. Approximately 13%-21% of patients received ibrutinib following first-line therapy. Most ibrutinib discontinuation was due to progression followed by toxicity/adverse events. Upon discontinuation of ibrutinib, considerable variation in treatments was seen and no standard therapy identified. Given the limitations of current therapies, there is a need for additional second- and third-line treatments for patients with MCL. Quantitative assessments of clinical endpoints from real-world studies evaluating BTKI therapies are also warranted. Disclosures Yang: BeiGene, Ltd.: Employment. Lesher:Pharmerit: Employment. Lucas:Pharmerit: Employment. Caver:BeiGene, Ltd.: Employment. Tang:BeiGene, Ltd.: Employment.

Treatment of Multiple Myeloma Patients Progressing on Lenalidomide-Based Regimens

Treatment of Multiple Myeloma Patients Progressing on Lenalidomide-Based Regimens

The Impact of Different Mobilization Strategies in the Setting of Multiple Myeloma

INTRODUCTION Multiple myeloma (MM) is considered an incurable disease. Despite the introduction of novel agents allowed deeper response, high-dose chemotherapy and autologous stem cell transplantation (ASCT) remain the standard of care for patients (pts) in good clinical conditions. The most used strategies to mobilize stem cells from bone marrow (BM) into peripheral blood are high-dose cyclophosphamide (HD-CTX) plus G-CSF and G-CSF plus plerixafor (G-CSF+P). The goal of this retrospective study is to investigate whether the two different mobilization strategies have an impact on the clearance of monoclonal PCs in the apheresis products and on pts' outcome. PATIENTS AND METHODS We analyzed 62 pts (median age 61, range 41-75, 37 males and 25 women) diagnosed with MM and treated with ASCT between Mar 2014 and Mar 2018 at our Hematology Division (Pisa, Italy). All pts received induction therapy with at least 4 cycles of bortezomib, thalidomide and dexamethasone (VTD). 9/62 pts obtained a less than partial response (PR) and received lenalidomide-based regimens. After induction, 8 (12,9%) pts achieved complete remission (CR), 26 (41,9%) were in PR, 28 (45,2%) obtained a very good partial response (VGPR). 43/62 fit pts received HD-CTX (2-3 g/sqm) on day 1 followed by G-CSF (30 MU/day) started on day 4 until day 7, increased to 60 MU/day from day 8 until the end of apheresis. In 19/62 pts, after 4 days of G-CSF (60 MU/day) administration and not sufficient mobilization, we added plerixafor (0,24 mg/kgbw) for up to 4 consecutive days. In 43/62 pts we collected apheresis samples (10μl) analyzed through flow citometry to enumerate clonal residual PCs. The panel used to asses clonality included: CD138 Per-Cp, CD38 APC, CD19 PE-Cy7, CD45 APC-Cy7, cytoplasmic immunoglobulin K chain and L chain. RESULTS At the end of the peripheral blood stem cell (PBSC) collection, pts treated with HD-CTX presented a higher CD34+ absolute count (p=0.0489) and achieved the threshold of 5x106 CD34+ cells/kgbw in a significantly (p=0.006) higher percentage. We found a nearly significant (p=0.0517) lower count of CD34+ PBSCs in pts who received lenalidomide-based regimens before the mobilization. Performing flow citometry on apheresis samples, we observed that the number of the harvested clonal PCs showed a significant correlation (p=0.0115) with the occurrence of post-ASCT relapse. ROC curve analysis investigating the predictive effect of the number of pathological PCs on disease relapse showed an area under the curve of 0,6978 (95% CI 0.5392-0.8564; p=0.0267). Neither BM residual PCs detectable on BM biopsies performed before apheresis (r=-0.1323; p=0.609) nor the type of mobilization scheme (p=0.707) had an impact on the proportion of clonal PCs in the graft. Additionally, we did not observe any statistically significant difference in progression free- (PFS) (p=0.8276) and overall survival (OS) (p=0.2475) between the HD-CTX and G-CSF+P groups. DISCUSSION PBSC mobilization has a succession rate > 85%. Despite the use of HD-CTX to increase PBSC yields and decrease tumor burden, there is not clear evidence of a superior mobilization strategy. Additionally, HD-CTX has a not negligible toxicity and approximately 10% of the pts require hospitalization. Conversely, G-CSF+P is a safe and effective approach also in poor mobilizers. In our study, we observed a significative difference in the apheresis yields (p=0.0489) and in the percentage of pts who achieved the threshold of 5x106 CD34+ cells/kgbw (p=0.006) in favor of HD-CTX. Additionally, the detection of harvested residual clonal PCs could be a promising strategy to recognise pts more likely to relapse after ASCT. Nonetheless, we failed to demonstrate a superior effect of HD-CTX in the clearance of harvested clonal PCs, in agreement with the absence of a different pts' outcome amongst the two mobilization strategies. In conclusion, the choice between the two regimens is challenging and requires careful consideration of multiple factors. Overall, young fit pts, especially in the high-risk setting, should be treated with all appropriate modalities including chemiomobilization followed by double-ASCT. Conversely, in pts candidate to a single-ASCT it is reasonable to use G-CSF+P, since HD-CTX does not improve PFS and OS and add toxicity. The absence of an in-vivo purging effect on apheresis products of chemiomobilization further strengthens a chemotherapy-free mobilization. Disclosures Galimberti: Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau.

Analysis of the Efficacy of Thalidomide Plus Dexamethasone-Based Regimens in Patients With Relapsed/Refractory Multiple Myeloma Who Received Prior Chemotherapy, Including Bortezomib and Lenalidomide: KMM-166 Study

BackgroundFor patients with multiple myeloma (MM) that relapsed after treatment with bortezomib- and lenalidomide-based regimens, there were no other treatment options in Korea until 2016. We aimed to determine the efficacy of thalidomide plus dexamethasone-based regimens in patients with relapsed/refractory MM (RRMM). Patients and MethodsWe conducted a multicenter retrospective analysis in Korea for patients with RRMM treated with thalidomide-based regimens who previously received bortezomib and immunomodulatory agents (IMiDs), including thalidomide and lenalidomide. ResultsIn 47 patients with RRMM, the median age was 64 years and the median number of previous treatment lines, including bortezomib and IMiDs, was 3. Primary resistance to bortezomib and lenalidomide was observed in 12 (26%) and 8 (17%) patients, respectively. The most common regimen was a combination of thalidomide, cyclophosphamide, and dexamethasone. The overall response rate was 38%; 2 patients (4%) experienced a complete response, and 2 patients (4%) experienced a very good partial response. The overall response rate of patients previously exposed to thalidomide was 53%. The median progression-free survival was 5.9 months, and overall survival was 9.2 months. Patients with disease that responded to the thalidomide-based regimen had better progression-free survival compared to those who did not (median, 8.8 vs. 2.5 months; P = .008). The most common adverse events were anemia (51%) for hematologic toxicities and peripheral neuropathy (30%) for nonhematologic toxicities. ConclusionThalidomide-based regimens are potential salvage treatment options for patients with RRMM, even those with disease with prior resistance to IMiDs.

Lenalidomide-based induction and maintenance in elderly newly diagnosed multiple myeloma patients: updated results of the EMN01 randomized trial.

n the EMN01 trial, the addition of an alkylator (melphalan or cyclophosphamide) to lenalidomide-steroid induction therapy was prospectively evaluated in transplant-ineligible patients with multiple myeloma. After induction, patients were randomly assigned to maintenance treatment with lenalidomide alone or with prednisone continuously. The analysis presented here (median follow-up of 71 months) is focused on maintenance treatment and on subgroup analyses defined according to the International Myeloma Working Group Frailty Score. Of the 654 evaluable patients, 217 were in the lenalidomide-dexamethasone arm, 217 in the melphalan-prednisone-lenalidomide arm and 220 in the cyclophosphamide-prednisone-lenalidomide arm. With regards to the Frailty Score, 284 (43%) patients were fit, 205 (31%) were intermediate-fit and 165 (25%) were frail. After induction, 402 patients were eligible for maintenance therapy (lenalidomide arm, n=204; lenalidomide-prednisone arm, n=198). After a median duration of maintenance of 22.0 months, progression-free survival from the start of maintenance was 22.2 months with lenalidomide-prednisone vs. 18.6 months with lenalidomide (hazard ratio 0.85, P=0.14), with no differences across frailty subgroups. The most frequent grade ≥3 toxicity was neutropenia (10% of lenalidomide-prednisone and 21% of lenalidomide patients; P=0.001). Grade ≥3 non-hematologic adverse events were rare (<15%). In fit patients, melphalan-prednisone-lenalidomide significantly prolonged progression-free survival compared to cyclophosphamide-prednisone-lenalidomide (hazard ratio 0.72, P=0.05) and lenalidomide-dexamethasone (hazard ratio 0.72, P=0.04). Likewise, a trend towards a better overall survival was noted for patients treated with melphalan-prednisone-lenalidomide or cyclophosphamide-prednisone-lenalidomide, as compared to lenalidomide-dexamethasone. No differences were observed in intermediate-fit and frail patients. This analysis showed positive outcomes of maintenance with lenalidomide-based regimens, with a good safety profile. For the first time, we showed that fit patients benefit from a full-dose triplet regimen, while intermediate-fit and frail patients benefit from gentler regimens. ClinicalTrials.gov registration number: NCT01093196.

Clinical and equipment-related factors associated with the adequate peripheral blood stem cell collection in autologous transplant at a tertiary cancer center in Kerala - A retrospective cohort study

BackgroundPBSC collection using apheresis is the preferred source of hematopoietic stem cells transplantation. However, apheresis procedures fail to harvest adequate CD34 yield in 5 to 40% of patients during the first collection. Therefore, this study aimed to study both the clinical- and equipmentrelated factors influencing CD34 yield among the autologous patients and to compare the collection efficiency of two apheresis equipments(Haemonetics MCS+ and Terumo Spectra Optia). MethodsRetrospective analysis of 69 patients underwent PBSC collection from 2015 to 2018. Frequency, clinical- and equipment-related factors responsible for adequate CD34+ cells (≥2 x106 cells/kg) yield during the first collection was studied. Factors such as collection efficiency, percentage platelet loss and percentage hemoglobin loss were considered to compare the two apheresis system. ResultsTwo-third (72%) patients of the study population had adequate CD34 stem cells yield during the first collection. Factors such as exposure to lenalidomide-based pretreatment regimen, peripheral blood WBC count and CD34 count are associated with the adequate CD34 yield. Optia had a slightly better collection efficiency than MCS+ (50 and 44; p=0.37). Optia had lower product volume (237 vs 298 ml) and lesser procedure duration (277 vs 360 min), whereas the median Hb loss (3.0% and 2.3%) and mean platelet loss (49% and 34%) were higher with MCS. ConclusionThis study infers that the collection efficiency of both the equipments in collecting CD34 stem cells was similar. However, during PBSC collection, procedures using Optia can be preferred to MCS+ on the patients with risk of anemia and thrombocytopenia.

Treatment patterns in patients with multiple myeloma (MM): A retrospective study using Medicare data.

e19506 Background: MM is characterized by repeated relapses and refractoriness and is managed by successive lines of therapies (LT) each typically resulting in shorter response duration over prior LT. This study describes current MM treatment (tx) landscape in US clinical practice. Methods: Adult MM patients (pts) with continuous Medicare Part A, B, and D coverage initiated on 1st LT (1L), without stem cell transplant, were identified in the Medicare Research Identifiable Files (2012-2016). Claims for any MM tx within 60 days of the 1st tx constituted the tx regimen of an LT. End of LT was defined as a claim for a new MM tx &gt; 60 days post LT initiation (tx augmentation or switch), discontinuation of all tx in a regimen for &gt; 90 consecutive days, end of Medicare coverage/data or death. From 1L to 3L, overall survival (OS), LT duration (DoT), tx regimens and sequences were assessed. Results: 8374 MM pts with 1L (median [med] age = 76 years at 1L; 55% female) were analyzed. Over a med follow-up of 20 months (mos) from 1L (med 1L DoT = 5.6 mos), 2849 pts received a 2L (med 2L DoT = 5.6 mos) and 978 received a 3L (med 3L DoT = 4.7 mos). The most prominent tx regimens were bortezomib/corticosteroids (CS; VD) in 1L, and lenalidomide/CS (RD) in 2L and 3L. The most prevalent tx sequence was 1L VD, 2L RD and 3L VD. The 1- and 2-year OS rates were 81% [95% confidence interval: 81-82] and 68% [67-69] from 1L initiation, 80% [78-82] and 64% [61-66] from 2L, and 73% [69-76] and 55% [51-60] from 3L initiation, respectively. Conclusions: MM Medicare pts mainly cycle through bortezomib- or lenalidomide-based regimens in front LT; newer agents gain more usage in later LT. A better understanding of tx options and sequencing is warranted to prolong survival. [Table: see text]

Health-Related Quality of Life in Transplant Ineligible Newly Diagnosed Multiple Myeloma Patients Treated with Either Thalidomide or Lenalidomide-Based Regimen Until Progression (HOVON-87/NMSG18 Study): A Prospective, Open-Label, Multicenter, Randomized, Phase 3 Study

Background: The overall survival of patients with Multiple Myeloma has improved due to effective, often continuous, therapy. However, knowledge on the impact of long term treatment on health-related quality of life (HRQoL) is limited. Methods: The HOVON87/NMSG18 study was a prospective, randomized, phase 3 study of newly diagnosed transplant ineligible multiple myeloma patients, comparing melphalan-prednisolone in combination with thalidomide or lenalidomide, followed by thalidomide or lenalidomide maintenance therapy (MPT-T or MPR-R). The EORTC QLQ-C30 and MY20 questionnaires were completed by patients at baseline, after 3 and 9 induction cycles and after 6 and 12 months of maintenance therapy. Linear mixed models and minimal important differences were used for between and within treatment arm HRQoL evaluation. Findings: 596 of 637 eligible patients participated in HRQoL reporting. Patients in both arms reported clinical relevant improvement in global QoL, future perspective, role and emotional functioning and the summary score, and less fatigue and pain, in general occurring after 6 to 12 months of maintenance only and independent of WHO performance at baseline. MPR-R treated patients reported clinically relevant worsening of diarrhoea and MPT-T treated patients reported a higher incidence of neuropathy. Patients who remained on lenalidomide maintenance therapy for at least 3 months reported clinically meaningful improvement in global QoL, role functioning and the summary score over time, without any clinical meaningful deteriorations. In contrast, patients on thalidomide reported clinically relevant worsening of peripheral neuropathy. Interpretation: Treatment with both thalidomide- and lenalidomide-based regimens improved HRQoL, in general reaching clinical relevance during maintenance therapy only. Clinical relevant diarrhea was reported by lenaldiomide-treated and clinical relevant PNP by thalidomide-treated patients. Trial Registration Number: The study was registered at www.trialregister.nl NTR1630. Funding Statement: Dutch Cancer Society KWF VU-2008 4246, Celgene Declaration of Interests: AW reports that the study was supported by Celgene and receives honoraria Takeda and grant from Amgen. MH reports compensation for work related to the study from NTNU Department of Cancer Research and Molecular Medicine and receives grant from Celgene Aps. MS receives personal fees from Celgene, Amgen, Janssen and Takeda. SZ receives research funding from Celgene, Janssen, Takeda and Amgen and serves on advisory board for Celgene, Janssen, Takeda and Amgen. LKN has received grants from Celgene, Janssen, Amgen and Takeda, during the conduct of the study. NA receives research funding from Celgene, Janssen, Takeda and Amgen. PS receives grants from Takeda, Karyopharma, and grants and personal fees from Celgene, Janssen-Cilag. M-DL has received personal fees from Celgene. U-HM has received lecture honoraria from Amgen, Takeda, Janssen, Mundipharma, Oncopeptides and serves on advisory board for Amgen. NvdD receives grants from Celgene, Janssen pharmaceuticals, Novatis, Amgen and BMS and serves at the advisory board for Celgene, Janssen pharmaceuticals, Novartis, Amgen, Takeda, BMS, Bayer, Servier. All other authors declare no conflicting interest. Ethics Approval Statement: The study protocol was approved by the Ethics Committee and conducted in accordance with the ethical principles of the Declaration of Helsinki and the Good Clinical Practice Guidelines. The authors obtained written informed consent from all participants.

Real-World Treatment Patterns, Outcomes, and Healthcare Resource Utilization in Relapsed or Refractory Multiple Myeloma: Evidence from a Medical Record Review in France.

Background Limited data are available from real-world practices in Europe describing prevailing treatment patterns and outcomes in relapsed/refractory multiple myeloma (RRMM), particularly by cytogenetic risk. Methods A retrospective medical record review was conducted in 200 RRMM patients in France. From first relapse, patients were assessed on second-/third-line treatments, progression-free survival (PFS), overall survival (OS), and healthcare utilization. Results Fifty-five high risk and 113 standard risk patients were identified. Overall, 192 patients (96%) received second-line therapy after relapse. Lenalidomide-based regimens were most common (>50%) in second line. Hospitalization incidence in high risk patients was approximately twice that of standard risk patients. From Kaplan-Meier estimation, median (95% CI) second-line PFS was 21.4 (17.5, 25.0) months (by high versus standard risk: 10.6 [6.4, 17.0] versus 28.7 [22.1, 37.3] months). Among second-line recipients, 47.4% were deceased at data collection. Median second-line OS was 59.4 (38.8, NE) months (by high versus standard risk: 36.5 [17.4, 50.6] versus 73.6 [66.5, NE] months). Conclusions The prognostic importance of cytogenetic risk in RRMM was apparent, whereby high (versus standard) risk patients had decidedly shorter PFS and OS. Frequent hospitalizations indicated potentially high costs associated with RRMM, particularly for high risk patients. These findings may inform economic evaluations of RRMM therapies.

Survival Outcome of Salvage Therapy with Second-Generation Novel Agents in Patients with Relapsed and Refractory Multiple Myeloma in Routine Clinical Practice

Survival outcome of patients with multiple myeloma (MM) has been markedly improved by the introduction of novel agents such as bortezomib, thalidomide, and lenalidomide over the past decade. Recent clinical studies have shown further improvement by second-generation agents, namely carfilzomib, ixazomib, pomalidomide, elotuzumab, and daratumumab. However, the prognosis of patients who became refractory to both bortezomib and lenalidomide was extremely poor, and the efficacy of the second-generation agents in such patient remains unclear in routine clinical practice. In this study, we analyzed the outcome of MM patients in terms of overall survival (OS) and survival time after salvage therapy. A total of 174 patients (89 male and 85 female) treated between 2003 and 2017 were enrolled. The median age was 69 years old (range 35-89). The type of M protein was IgG in 93, IgA in 35, IgD in 10, Bence Jones type in 30, and non-secretory type in 5 patients, respectively. The international staging system (ISS) stages I, II, and III were 32, 66, and 63 patients, respectively. There were 100 patients with normal serum LDH and 39 with high LDH. As for initial therapy, 62 patients were treated with conventional chemotherapy, 83 with bortezomib-based regimens, 7 with lenalidomide-based regimens, and 22 with bortezomib + lenalidomide + dexamethasone. Forty-seven patients received autologous stem cell transplantation in the upfront setting. During the observation period 120 patients relapsed and 6 were refractory to initial therapy, and 38 patients were treated with conventional chemotherapy and 58 with the first-generation novel agents such as bortezomib, lenalidomide, or thalidomide as salvage therapy. The remaining 30 patients were further treated with the second-generation novel agents such as carfilzomib in 21, ixazomib in 5, pomalidomide in 6, elotuzumab in 4, or daratumumab in 8 patients after refractory to bortezomib and lenalidomide. The median progression-free survival was 17.7 months and the median OS was 51.0 months from initial therapy. Regarding the outcome according to salvage therapy, the median OS was 22.0 months for conventional chemotherapy group, 46.4 months for first-generation agent group, and 98.7 months for second-generation agent group (p<0.0001). The survival of the second-generation group was longer compared with the first-generation group in both transplanted (median OS, 80.5 vs 118.3 months) and non-transplanted patients (39.2 vs 56.6 months). In patients who received the first-generation agents as initial therapy, the median OS was 45.1 months for the first-generation group and 71.5 months for the second-generation group. In the survival time after salvage therapy, the median survival was 18.6 months, and there was no significant difference by initial therapy (16.8 months for conventional chemotherapy group and 20.1 months for novel agent group). According to salvage therapy, the median survival after salvage therapy was 7.5 months for conventional chemotherapy group, 20.4 months for first-generation agent group, and 29.5 months for second-generation agent group (p<0.001, Figure). The survival benefit after salvage therapy with the second-generation agents was also observed in both transplanted (median survival after salvage, 29.5 vs 69.8 months) and non-transplanted patients (18.6 vs 23.6 months). In patients who received the first-generation agents as initial therapy, the median survival after salvage was 25.0 months for the first-generation group and 29.5 months for the second-generation group, and again survival time was longer in the second-generation group. Regarding the risk factors, the median survivals after second-generation novel agent therapy were not reached, 69.8, and 14.8 months in the ISS I, II, and III stages, respectively, and were 69.8 and 14.8 months in normal and high LDH groups, respectively. Thus, our results have demonstrated that the second-generation novel agents significantly prolonged survival in relapsed and refractory patients regardless of the use of the first-generation agents. However, the survival benefit was mostly observed in standard risk and transplanted patients but not in high-risk patients. Therefore, further studies are needed to establish more effective strategies using the next generation agents in routine clinical practice. DisclosuresNo relevant conflicts of interest to declare.

Lenalidomide Plus Hypomethylating Agent for Acute Myeloid Leukemia (AML) with Recurrent Genetic Abnormalities -AML with Inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, Mecom

Intro: Acute myeloid leukemia (AML) is a heterogeneous clonal hematopoietic neoplasm. The cytogenetic changes associated with AML impact response rate and survival, and is one of the most important independent prognostic factors. AML with inv(3)(q21.3q26.2) or; GATA2, MECOMaccounts for 1-2% of all forms of AML. This form is associated with a younger age at diagnosis, poor response to standard induction chemotherapy, and very poor long-term prognosis with an overall survival of <10%. Unfortunately, traditional intensive induction chemotherapy has a reported remission rates of 10-20% (Raya et al. Hematology 2015;20(8):435-441). Clearly, alternative chemotherapy approaches are needed to effectively treat AML with inv(3). We previously presented a case report of a patient with inv(3) receiving induction chemotherapy with a combination of a hypomethylating agent (HMA) with lenalidomide and achieving remission (Platzbecker, et al. Leukemia 2013;27:1813-1819, Foucar et al. American Journal of Clinical Pathology2015; 144(1): 6-18). To further address the effectiveness of this regimen, we performed a retrospective cohort study comparing outcomes with HMA plus lenalidomide to standard intensive induction therapies in newly diagnosed and relapsed/refractory AML with inv(3).Methods: We conducted a single-center, IRB-approved, retrospective cohort analysis of 939 patients who received therapy for AML at the University of Michigan between March 2005-June 2018. 15/939 (1.6%) patients tested positive for inv(3)(q21.3q26.2), and they were divided into two cohorts: a lenalidomide-based regimen or other chemotherapy induction approaches. Data abstraction of patient, disease and treatment-related variables was performed through manual chart review. The primary outcome was overall response rate (ORR), reported as the combination of complete remission (CR) and complete remission with incomplete count recovery (CRi). Secondary endpoints included overall survival (OS), 30- and 60-day mortality, event free survival (EFS), and duration of response. All data were analyzed using SPSS software, version 24.0 (SPSS, Inc., Chicago, IL).Results: In total, 15 patients were positive for inv(3)(q21.3q26.2) and underwent treatment at the University of Michigan. 4/16 (25%) received lenalidomide and HMA as primary therapy. Patient demographics and lab values at diagnosis are shown in Table 1. 4/4 (100%) of patients receiving lenalidomide with HMA as first line therapy achieved CR/CRi while 3/11 (27.3%) of patients receiving other chemotherapeutic agents initially achieved CR/CRi (p=0.0256). Duration of response was numerically longer in patients receiving lenalidomide-based therapies (7.4 months vs. 1.45 months; p=0.057). Primary and secondary outcomes in patients receiving lenalidomide plus HMA and other chemotherapies are shown in Table 2. 2/13 patients requiring salvage therapy received lenalidomide with HMA. Both of these patients achieved CR/CRi, while 3/11 (27.3%) of patients receiving other chemotherapy achieved CR/CRi. Combining initial and salvage inductions, 6/6 (100%) achieved CR/CRi with lenalidomide with HMA versus 6/22 (27.3%) with other chemotherapy (p=0.0025).Discussion: AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOMis notorious for a poor response to standard induction chemotherapy and a reported remission rate of 10-20% with traditional chemotherapy (Raya et al. Hematology 2015;20(8):435-441).In this cohort, all patients who received lenalidomide with or without a HMA achieved CR/CRi compared to 27% of patients receiving other chemotherapy. Importantly, the median duration of response with lenalidomide and HMA was longer than traditional chemotherapy, although not statistically significant, likely due to the small sample size. The high ORR and reasonable duration of response could allow for potentially curative alloHCT in these high-risk AML patients. Our study is limited by the small sample size due to the rarity of this AML subtype, but the initial data suggests that lenalidomide plus HMA is a promising approach for patients with AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM. A multicenter, prospective trial should be considered to compare the efficacy of traditional cytotoxic chemotherapy approaches versus lenalidomide plus HMA to improve outcomes in this subtype of AML. [Display omitted] DisclosuresBixby:GlycoMimetics: Research Funding.

Survival Comparison of Three Treatment Regimens of POEMS Syndrome: A Single-Center Retrospective Study

OBJECTIVE: POEMS syndrome is a rare plasma cell dyscrasia and there is currently no standard treatment. Current treatments include melphalan, autologous stem cell transplantation (ASCT) and novel regimens. However, the efficacy of these treatments has not previously been retrospectively compared in large cohorts. Therefore, this study aims to compare the efficacy and survival of three treatment regimens in patients with POEMS syndrome in our 18-year cohort.METHODS: We retrospectively analyzed the clinical records of 347 patients with newly diagnosed POEMS syndrome who were diagnosed and treated in our hospital from January 2000 to December 2017 with complete treatment and follow-up data. Patients were divided into three groups according to the initial first-line treatment regimen: melphalan + dexamethasone (MDex, N = 79) for 9 months, autologous stem cell transplantation (ASCT, N = 165), or lenalidomide + dexamethasone for 1 year (LDex, N= 103). Hematologic complete remission rates (CRH), vascular endothelial growth factor (VEGF) complete remission rates (CRV), and neurological remission rates (RN) were compared for three regimens, as well as progression-free survival (PFS) and overall survival (OS). Hematologic complete remission was negative IFE and no FLC in serum or urine. The VEGF complete remission was normalized VEGF (<600 pg/ml). The neurological response was defined as the reduction of ONLS by more than 1 point. Remission rates were compared by Pearson ӽ 2 test or Fisher's exact test. Survival curves were plotted by the Kaplan-Meier method and tested using a log-rank test. Subgroup analyses were based on risk stratification and heterogeneous baseline characteristics between treatment groups.RESULTS: Patients in the ASCT group achieved significantly higher rates of CRV (66.2%), which were superior to the MDex group (38.5%, p = 0.001) and the LDex group (47.7%, p = 0.006). There were no significant differences in CRH and RN between the three groups: CRH (MDex 37.7% vs ASCT 49.7% vs LDex 47.5%, p = 0.244) and RN (MDex 100% vs ASCT 91.% vs LDex 93.8%, p = 0.234). However, the proportion of low risk patients in the ASCT group was significantly higher than that in the MDex and LDex groups (44.2% vs 22.8% & 26.2%, p=0.001). Therefore, we performed a subgroup analysis. Subgroup analysis showed that the CRV in the ASCT group was similar to that in MDex and LDex groups in the low-risk group (p = 0.222), but there was a significant advantage in the middle- and high-risk patients (p = 0.001). After a median follow-up of 45 months, a total of 49 deaths occurred and 50 patients developed disease progressions but remained alive. The 3-year PFS was 83.7% for MDex group, 87.9% for ASCT group, and 65.2% for LDex groups. The 3-year OS was as follows: MDex group 90.6%, ASCT group 94.4%, and LDex group 81.6%. The ASCT group achieved a better PFS than the LDex group (p = 0.003), while the three groups had no significant differences in 3-year OS (p = 0.069).CONCLUSION: All three treatment regimens have achieved good efficacy and survival in the treatment of POEMS syndrome. Compared with melphalan and lenalidomide-based regimens, patients at medium to high risk may benefit more from autologous transplantation. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.