Transplant-ineligible Multiple Myeloma Patients Research Articles

Upfront treatment for newly diagnosed transplant-ineligible multiple myeloma patients: A systematic review and network meta-analysis of 14,533 patients over 29 randomized clinical trials.

Choice of treatment for newly diagnosed transplant-ineligible multiple myeloma poses a difficult task due to an ever-increasing plethora of different regimens. Attempting to clarify this subject, we performed a systematic review and Bayesian network meta-analysis of 29 randomized clinical trials, enrolling 14,533 patients, and comparing 25 different treatment regimens regarding overall survival(OS), progression-free survival(PFS), complete response(CR), overall response rate(ORR) and toxicity. Head-to-head comparisons for all regimens and ranking of best treatments are reported. OS analysis showed superiority of lenalidomide(R) and bortezomib(V) containing regimens over thalidomide(T) protocols (e.g. Rd/CTD-HR:0.7;95%CrI:0.53-0.93, VMP/TD-HR:95%0.45;CrI:0.29-0.69). Concerning PFS, daratumumab(D) plus V (Dara-VMP) showed superior results over R (e.g. Dara-VMP/MPR-HR:0.52;95%CrI:0.34-0.77), V plus T (Dara-VMP/VTd-HR:0.56;95%CrI:0.37-0.65) and T (Dara-VMP/CTD-HR:0.34;95%CrI:0.23-0.49) containing regimens. Also, VRd and VMPT-VT performed well over other regimens. Dara-VMP showed superior response rates over R (ORR Dara-VMP/MPR-RR:6.27;95%CrI:2.18-18.95, CR Dara-VMP/MPR-RR:1.53;95%CrI:1.21-1.96) and T (ORR Dara-VMP/MPT-T-RR:4.05;95%CrI:1.19-13.26, CR Dara-VMP/MPT-T-RR:1.42;95%CrI:1.09-1.85; ORR Dara-VMP/CTD-RR:2.72;95%CrI:1.2-6.31, CR Dara-VMP/CTD-RR:1.2;95%CrI:1.05-1.36) including a higher rate of complete remission even when compared to VRd (RR:1.29;95%CrI:1.01-1.66). A higher rate of grade 3-4 adverse events was found for RD and CPR (thrombotic); VTd, VTP and VMPT-VT (neurological); RD and VAD (infectious); MPR-R and VAD (hematological); Vd and VTd (gastrointestinal); VAD, VMPCc and RD (cardiovascular). These results confirm obsolescence of classical regimens (such as VAD and MP) while pointing out benefits in efficacy resulting from incorporation of quadruplets and triplets combining new agents (Dara-VMP, VRd and VMPT-VT) and supports current rational of treatment until progression or prohibitive toxicity, especially when including lenalidomide. Based on this data, we would recommended incorporation of strategies combining novel agents (monoclonal antibodies, immunomodulatory imide drugs and proteasome inhibitors) in triplets or quadruplets and/or those comprising long term use of lenalidomide as standard frontline treatments. Moreover, this study settles daratumumab's place as an attractive alternative for upfront treatment.

First-line therapy with either bortezomib-melphalan-prednisone or lenalidomide-dexamethasone followed by lenalidomide for transplant-ineligible multiple myeloma patients: a pooled analysis of two randomized trials.

Bortezomib-melphalan-prednisone (VMP) and continuous lenalidomide-dexamethasone (Rd) represent the standard treatment of transplant-ineligible patients with newly diagnosed multiple myeloma (MM). To date, no randomized trial has compared VMP to Rd, and there is no evidence of the optimal treatment for newly diagnosed MM, particularly in patients with high-risk cytogenetics [del(17p), t(4;14) or t(14;16)]. We pooled together data from patients with newly diagnosed MM treated with VMP or Rd induction followed by lenalidomide maintenance 10 mg (Rd-R) enrolled in the GIMEMA-MM-03-05 and EMN01 trials, to evaluate the efficacy of these treatments in different subgroups of patients, focusing on those with standard- and high-risk cytogenetics. Overall, 474 patients were analyzed (VMP: 257 patients; Rd-R: 217 patients). No differences in progression-free survival (hazard ratio=0.96) and overall survival (hazard ratio=1.08) were observed between standard-risk patients treated with VMP or Rd-R, whereas among the high-risk patients, the probabilities of progression (hazard ratio=0.54) and death (hazard ratio=0.73) were lower in the patients treated with VMP than in those treated with Rd-R. In particular, standard-risk patients >75 years benefited less from VMP than from Rd-R (hazard ratio for progression-free survival=0.96; hazard ratio for overall survival=1.81). In this non-randomized analysis, VMP and Rd-R were equally effective in younger (≤75 years), standard-risk patients, while older ones (>75 years) benefited more from Rd-R. In high-risk patients, VMP improved progression-free survival and overall survival irrespective of age. The source trials are registered at ClinicalTrials.gov (NCT01063179 and NCT01093196).

PS1405 USE OF POMALIDOMIDE-BASED REGIMENS IN RELAPSED/REFRACTORY MULTIPLE MYELOMA IN FOUR EUROPEAN COUNTRIES – FINDINGS FROM PREAMBLE

Background: Approval of new standards of treatment in cancer is preceded by phase III clinical trials that provide information on safety and efficacy. Nevertheless, excessive rigidity eligibility criteria may compromise extrapolation of results to the target population (external validity). Klausen et al (Leukemia 18), report that over 60% of patients diagnosed of multiple myeloma (MM) would not fulfill eligibility criteria for clinical trials. So, safety and efficacy data may differ from clinical trials to real life. Aims: The aim of our study is to assess the correlation between patient comorbidities by Cumulative Illness rating score (CIRS) score and eligibility in clinical trials. Methods: Eligibility criteria of 3 commercial (VISTA, FIRST, ALCIONE) and 2 academic clinical trials (GEM05MAS65 and GEM10MAS65) were verified for all patients with newly diagnosed transplant-ineligible multiple myeloma (TIMM) at Hospital Universitario de Araba (Spain). CIRS score was calculated for all de patients. Results: From February 2010 to December 2017, 143 MM patients were diagnosed. Of them, 92 patients (64%) were transplant-ineligible and were treated with a bortezomib-melphalan-prednisone scheme. For TIMM patients median age was 77 years old, higher than published trials (median age VISTA: 71, FIRST: 73, ALCIONE: 71, GEM05: 73, GEM10: 75). CIRS score identify different prognostic groups in overall survival: CIRS <4: 52.3 months; CIRS 4 to 8: 57 months and CIRS> 8: 13.5 months (p: 0.017) (figure 1). Applying eligibility criteria, clinical trials result in high exclusion rates: VISTA: 75% FIRST: 70%; ALCIONE 75%; GEM05: 75%; GEM10: 77%. Considering only external validity criteria, exclusion rate was slightly lower: VISTA: 59%; FIRST: 46%; ALCIONE 59%; GEM05: 58%; GEM10: 62%. Regarding comorbidities, no correlation among CIRS score and possibility to be included in clinical trials was observed, although high exclusion was observed for patients with CIRS score >8 vs ≤8 (VISTA 77% vs. 54%; FIRST: 50% vs. 44%; ALCIONE 67% vs. 56%; GEM05: 72% vs. 54%; GEM10: 83% vs. 57%, respectively) (table 1). The presence of grade 3 or 4 comorbidities was not associated with higher exclusion rates.Summary/Conclusion: Eligibility criteria in multiple myeloma clinical trials are excessively restrictive, and do not reflect comorbidities of the patients. Safety and efficacy of recently approved drugs and combinations schemes for treatment of newly diagnosed TIMM in real life may differ from those reported on clinical trials. Selection criteria of clinical trials must be updated and adapted to reality.

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 Outcomes with Bortezomib-Containing Regimens and Lenalidomide Plus Dexamethasone for the Treatment of Transplant Ineligible MM Patients: A Multi-Institutional Report from the National Myeloma Canada Research Network (MCRN) Database

Introduction: Bortezomib-containing regimens (BCRs) have been the standard frontline approach for the treatment of transplant ineligible multiple myeloma (TIMM) patients in Canada for many years. Based on recent randomized clinical trial results lenalidomide and dexamethasone (Ld) has become another provincially funded option in Canada in the same therapeutic space. We aimed to compare the effect of BCRs and Ld for the treatment of TIMM using the newly-formed Myeloma Canada Research Network Multiple Myeloma Database (MCRN-MM-DB) project. This web-based centralized platform can track and characterize real-world outcomes of patients treated at major Canadian institutions and includes both legacy data dating back to 2007 (from 4 centres) as well as ongoing prospective data collection (from 11 centres) analyzed up to 01/07/18. Patients and Methods: The primary objective was to assess the ORR, PFS and OS for TIMM patients treated with CyBorD/CyBorP, Ld, VMP or VD/VP, each given as reported previously but with dose-adjustments at the discretion of the treating physician to maintain patients on therapy. The two-sided Fisher exact test was used to test for differences between categorical variables. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test; a p value of <0.05 was considered significant. Results: 842 TIMM patients were evaluated. Clinical characteristics are shown in Table 1. Median OS and PFS for the entire cohort were 54.1 and 20.4 months, respectively. ORR and ≥VGPR better rates were 83% and 52% for the entire cohort. A ≥VGPR rate of 53%, 46%, 56% and 51% were observed for patients treated with CyBorD/P, VMP, Ld and VD/VP, respectively (p=0.3). The median PFS was longer for Ld patients (25 months) compared to CyBorD/CyBorP, VMP and Vd/VP (19.3, 20.5 and 13.7 months, respectively), (p=0.03, Fig 1a); there was no significant difference in PFS between the 2 different alkylating-agent containing regimens when combined with bortezomib + steroids (CyBorD/P vs VMP, p =0.9). Median OS was 51, 59.5, 29.4 and 66.5 months for those patients treated with CyBorD/CyBorP, VMP, VD/VP and Ld, respectively (p=0.07, Fig 1b). When the OS and PFS for CyBorD/P (typically given for a fixed duration of 9 cycles) were compared with Ld in a subset analysis, the p-values were 0.08 and 0.008, respectively. Conclusions: 1) OS was not significantly different in patients treated with either a bortezomib-containing triplet that includes an alkylator + steroid or continuous Ld. 2) The BCR triplets and Ld were more efficacious than the bortezomib + steroid doublet (VD/VP) for both OS and PFS although, the small sample size and adverse factors, such as frailty and comorbidities, may have influenced the findings. 3) The results in the real-world setting, i.e., a median PFS in the range of 1.5-2 years and median OS of 4.5-5.5 years, confirm triplet-based BCRs and Ld as current valid standards of care for frontline therapy in TIMM. 5) This study confirms the utility of a large comprehensive national database to benchmark current results for comparison with newer regimens as they are introduced into the Canadian therapeutic landscape. [Display omitted] DisclosuresArleigh:Celgene: Honoraria; Janssen: Honoraria. Sebag:Janssen Inc.: Membership on an entity's Board of Directors or advisory committees; Amgen Canada: Membership on an entity's Board of Directors or advisory committees; Takeda Canada: Membership on an entity's Board of Directors or advisory committees; Celgene Canada: Membership on an entity's Board of Directors or advisory committees. Leblanc:Celgene Canada: Membership on an entity's Board of Directors or advisory committees; Janssen Inc.: Membership on an entity's Board of Directors or advisory committees; Amgen Canada: Membership on an entity's Board of Directors or advisory committees; Takeda Canada: Membership on an entity's Board of Directors or advisory committees. Louzada:Janssen: Honoraria; Celgene: Honoraria; amgen: Honoraria; pfizer: Honoraria. Venner:Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Takeda: Honoraria.

The Survival of Transplant Ineligible Multiple Myeloma Patients Treated with Bortezomib-Based Chemotherapy Is Affected By the Patient Fitness

BackgroundFrail patients who are in a poor perfomance status and have serious comorbidities or abnormal laboratory results comprise about one-third of the transplant ineligible multiple myeloma (MM). These patients, most of the cases, are excluded from the clinical studies. By far, the outcome of the real world data according to the patients' fitness in transplant ineligible MM patients is limited.MethodFour hundred and fifteen patients with MM who have been treated with bortezomib, melphalan and prednisone (VMP) as a first-line treatment were retrospectively analyzed. 4 factors included into the frailty scores were Age, ECOG PS (Eastern cooperative group performance status), eGFR (estimated glomerular filtration rate), and number of comorbidities (heart disease, lung disease, liver disease, cerebrovascular disease, diabetes mellitus). These factors were di- or trichotomized by the reference of previously published papers and the meaningful cut-offs in our data. The points given to each variables were after the following criteria: Age < 70 (point 0), 70-79 (point 1), ≥ 80 (point 2); ECOG PS 0-2 (point 0), 3-4 (point 2); eGFR ≥ 60 mL/min/1.73 m2 (point 0), < 60 mL/min/1.73 m2 (point 1); comorbidity 0-1 (point 0) and ≥ 2 (point 1). Patients were further classified by frailty scores: fit (points 0-2), unfit (points 3-5) and frail (point 6).ResultThe median follow-up duration was 26.72 months (range 0.37 - 180.20 months). All of the factors including the Age ≥ 80, ECOG PS 3-4, eGFR < 60 mL/min/1.73 m2, and comorbidity ≥ 2 statistically significant for overall survival (OS) by univariate analysis. In multivariate analysis, ECOG PS 3-4 and eGFR < 60 mL/min/1.73 m2 remained statistically significant for OS and Age ≥ 80 was marginally significant for OS (Table 1). The response rates by the fit, unfit, and frail were as follows: 77.5% (148/191), 71.4% (55/77), and 0% (0/2) (P= 0.028). The 3-year overall survival rates by the frailty were 66%, 41%, and 0% in the fit, unfit or frail patients respectively and showed statistically significant difference (Figure 1 and Table 2, P= 0.000). The comparison of the frailty score with international staging system (ISS) and revised ISS (R-ISS) revealed statistical significance of all of the prognostic systems affecting OS by the univariate analyses but R-ISS and frailty score remained significantly affecting OS.ConclusionUnfit and frail patients showed a significant decrease in OS compared to fit patients. But there was no difference between the unfit and fit patients in terms of response rate in patients with transplant ineligible MM patients who have received bortezomib-containing regimen. Treatment of the unfit and frail patients needs more caution on toxicity management and appropriate dosing schedules to improve the survival outcome. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

The Revised International Staging System Compared to the Classical International Staging System Better Discriminates Risk Groups among Transplant-Ineligible Multiple Myeloma Patients

Background: The Revised International Staging System (R-ISS) has recently been introduced as a comprehensive prognostic score for multiple myeloma (MM). Validation of the R-ISS in patients treated outside of clinical trials is the focus of current investigations. The aim of this study was to test the prognostic role of the R-ISS in MM patients ineligible for autologous stem cell transplantation. Patients and Methods: A total of 102 newly diagnosed MM patients were analyzed. All patients were initially treated with thalidomide-based combinations. Results: An overall response rate was achieved in 77.4% patients. Both the International Staging System (ISS) and the R-ISS influenced the event-free survival and the overall survival (OS). However, the ISS was unable to discriminate patients in stages ISS1 and ISS2 regarding OS. On the contrary, the R-ISS clearly differentiated risk categories regarding OS and provided an improved discriminative power of 6.3% compared to the ISS. Furthermore, among the parameters that were significant in univariate analysis (presence of renal impairment, anemia, platelet count < 130 × 10⁹/l, and R-ISS), the multivariate model pointed to the R-ISS (p = 0.001) as the most important parameter influencing OS. Conclusion: The R-ISS represents a useful tool for risk stratification of transplant-ineligible MM patients and should be considered as a prognostic index in daily clinical practice.

Cardio-vascular Toxicity in Newly Diagnosed, Transplant-ineligible Multiple Myeloma Patients Treated With Carfilzomib, Cyclophosphamide and Dexamethasone: Results From an Integrated Analysis of 3 Phase I/II Trials

Cardio-vascular Toxicity in Newly Diagnosed, Transplant-ineligible Multiple Myeloma Patients Treated With Carfilzomib, Cyclophosphamide and Dexamethasone: Results From an Integrated Analysis of 3 Phase I/II Trials

Proteasome inhibitors in first-line treatment of transplant-ineligible multiple myeloma patients.

Since the turn of the century, many agents against multiple myeloma (MM) have been introduced into daily clinical practice. The development of further agents is ongoing and some of these will reach the point of use in clinical practice in the near future. As various treatment options become available, the selection of an appropriate treatment strategy for an individual patient becomes more important. Treatment selection and decision making are based on the following two apparently opposite factors: 1) generalized findings and evidence from clinical trials, and 2) disease risks and background of individuals, which are diverse among patients. Proteasome inhibitors (PIs) are central players in MM treatment. In this review, we summarize evidence for the efficacy and safety of a first generation PI, bortezomib, and discuss its advantages in controlling disease risks and myeloma-defining events in patients with transplant-ineligible, untreated, newly diagnosed MM (NDMM). We also highlight on recent knowledge regarding the use of second generation PIs such as carfilzomib and ixazomib in the treatment of transplant-ineligible, untreated NDMM.

Minimal residual disease monitoring and immune profiling in multiple myeloma in elderly patients

AbstractThe value of minimal residual disease (MRD) in multiple myeloma (MM) has been more frequently investigated in transplant-eligible patients than in elderly patients. Because an optimal balance between treatment efficacy and toxicity is of utmost importance in patients with elderly MM, sensitive MRD monitoring might be particularly valuable in this patient population. Here, we used second-generation 8-color multiparameter-flow cytometry (MFC) to monitor MRD in 162 transplant-ineligible MM patients enrolled in the PETHEMA/GEM2010MAS65 study. The transition from first- to second-generation MFC resulted in increased sensitivity and allowed us to identify 3 patient groups according to MRD levels: MRD negative (<10−5; n = 54, 34%), MRD positive (between <10−4 and ≥10−5; n = 20, 12%), and MRD positive (≥10−4; n = 88, 54%). MRD status was an independent prognostic factor for time to progression (TTP) (hazard ratio [HR], 2.7; P = .007) and overall survival (OS) (HR, 3.1; P = .04), with significant benefit for MRD-negative patients (median TTP not reached, 70% OS at 3 years), and similar poorer outcomes for cases with MRD levels between <10−4 and ≥10−5 vs ≥10−4 (both with a median TTP of 15 months; 63% and 55% OS at 3 years, respectively). Furthermore, MRD negativity significantly improved TTP of patients >75 years (HR, 4.8; P < .001), as well as those with high-risk cytogenetics (HR, 12.6; P = .01). Using second-generation MFC, immune profiling concomitant to MRD monitoring also contributed to identify patients with poor, intermediate, and favorable outcomes (25%, 61%, and 100% OS at 3 years, respectively; P = .01), the later patients being characterized by an increased compartment of mature B cells. Our results show that similarly to transplant candidates, MRD monitoring is one of the most relevant prognostic factors in elderly MM patients, irrespectively of age or cytogenetic risk. This trial was registered at www.clinicaltrials.gov as #NCT01237249.

Improved survival of older patients with multiple myeloma in the era of novel agents.

Multiple myeloma (MM) is the most common hematologic malignancy in Europe. Although remaining an incurable disease, substantial progress has been made within the last two decades. However, until recently, improvement in overall survival (OS) was only documented in younger, transplant-eligible patients. In this analysis, we retrospectively investigated the outcome of older patients with newly diagnosed MM in an unselected patient population with a special focus on the use of novel agents in a routine care community-based, non-university setting. A total of 107 patients older than 65 years of age or patients aged 60-65 years with relevant comorbidities precluding the use of autologous stem cell transplantation diagnosed with MM between 2000 and 2011 at the two largest non-university hospitals of Eastern Switzerland were analyzed. Patients were grouped into two six-year periods by date of initial diagnosis, 2000-2005 and 2006-2011. The median follow-up was 6.9 (range of 2.1 to 9.4) years. The median OS for the entire cohort was 3.0 years (95% confidence interval, 2.4-4.4). The median OS was significantly longer for patients in the 2006-2011 group (4.3 years) compared with the 2000-2005 group (2.6 years, p = 0.04). The 5-year estimated OS improved from 26% to 38%; 1-year survival was similar in both groups (86% in the 2000-2005 group and 84% in the 2006-2011 group respectively). The use of novel agents showed a statistically significant correlation with OS, whereas the impact of age was only of borderline significance. In conclusion, we demonstrate improved OS outcomes in an unselected population of older patients with MM during the last decade. This improvement is associated with an increased use of novel agents for the treatment of transplant-ineligible MM patients in daily clinical practice. Copyright © 2015 John Wiley & Sons, Ltd.

A Phase II Study of Modified Lenalidomide, Bortezomib, and Dexamethasone (RVD lite) for Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma

Background: Multiple myeloma (MM) is primarily a disease of older adults with a median age at diagnosis of 66 years. Despite significant improvements in patient outcomes, there is a lag in survival in older transplant-ineligible patients compared to their younger counterparts. Traditionally, melphalan and prednisone-based regimens were the most widely accepted treatment options in this older, transplant-ineligible population. More recently, the FIRST trial has explored the use of lenalidomide and dexamethasone in these patients. Here, we sought to incorporate optimal novel agent-containing regimens in transplant-ineligible, older patients that balance efficacy with toxicity. Building on our prior experience with RVD in predominantly younger patients, our study evaluated a 3-drug regimen of modified RVD in the transplant-ineligible population.Methods: Modified RVD (“RVD-lite”) was administered over a 35-day cycle. Lenalidomide was given as a single daily oral dose of 15 mg days 1-21; bortezomib 1.3 mg/m2 once weekly subcutaneously on days 1, 8, 15, and 22; and dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22 and 23 for patients ≤75 yrs and days 1, 8, 15, 22 for patients older than 75 yrs. Intravenous bortezomib was used only in cycle 1 for the first 10 patients for pharmacokinetic analysis. Eligibility requirements included ECOG performance status ≤ 2 and acceptable hepatic, renal and hematologic function. The primary objective was to evaluate the objective response rate (ORR) of modified RVD in transplant-ineligible patients. Secondary objectives included evaluation of the safety profile of modified RVD, progression free survival, overall survival, time to response, response duration, the response rate with respect to cytogenetics, and the pharmacokinetic profile of intravenous and subcutaneous bortezomib. Exploratory analysis will determine minimal residual disease (MRD) status by genotyping and correlate with outcomes in patients who achieve a VGPR or better.Results: Forty-one eligible patients have enrolled between 4/17/13 and 7/18/14, and of those 38 received at least one dose of therapy. Median age at study entry was 73 years (range 65-91) with 22 women and 16 men. ECOG performance status of patients enrolled was 0 in 19 (46.3%), 1 in 15 (36.6%), and 2 in 6 (14.6%) patients. The ISS stage was I in 15 (36.6%), II in 9 (22.0%), and III in 10 (24.4%) patients. Treatment-related toxicities were reported for 34 subjects. Fatigue was the most commonly reported toxicity occurring in 17/34 (50.0%), and of those 16/17 were grade 1 or 2 and manageable. Peripheral neuropathy of any grade was reported in 14/34 (41.2%) of patients including Grade 1 -7 (20.6%), 2 – 6 (17.6%), and 3 – 1 (2.9%). 12/34 (35.3%) reported edema of which 11/12 (91.7%) were grade 1. Grade 3 or greater toxicities included hypophosphatemia - 11 (32.3%), Rash - 4 (11.8%), and mood changes - 2 (5.9%). Pharmacokinetic data comparing intravenous and subcutaneous dosing of bortezomib has been completed and analysis is in process. At a planned interim analysis after 4 cycles that included 33 patients, the investigator-reported ORR of PR or better was 81.8% (CR -5, VGPR – 11, PR - 11, SD 3). Three patients withdrew from the study after less than 1 cycle. Of those, one withdrew for worsening adrenal insufficiency, one for rash attributed to lenalidomide, and one for an unrelated toxicity prompting withdrawal at the Investigator’s discretion. Five additional patients have enrolled but have not completed 4 cycles. Of those, responses thus far include 1 CR, 2 PRs, 1 SD, and 1 patient who has not completed one cycle at the time of this analysis. Exploratory data on bone marrow samples on patients achieving VGPR or better have been collected and analysis for MRD is in process.Conclusions: ModifiedRVD appears to be a well-tolerated and highly effective regimen in the transplant-ineligible population. The ORR rate after up to 4 cycles suggests that this combination at the modified doses and on a weekly schedule is very active. The side effect profile proved manageable and well-tolerated in an older population despite the variance of performance statuses at study entrance. Interim analysis of 38 patients suggests that alternative dosing and schedule of RVD may both improve tolerability and enhance clinical benefit in newly diagnosed, transplant-ineligible MM patients. DisclosuresLaubach:Onyx, Novartis, Millenium, Celgene: Research Funding. Huff:Celgene, Millenium: Consultancy. Basile:Celgene: Speakers Bureau. Ghobrial:Millennium/Takeda: Membership on an entity’s Board of Directors or advisory committees; Onyx: Membership on an entity’s Board of Directors or advisory committees; BMS: Membership on an entity’s Board of Directors or advisory committees; Celgene: Membership on an entity’s Board of Directors or advisory committees. Schlossman:Millennium: Consultancy. Munshi:Celgene, Onyx, Janssen, Sanofi-Aventi, Oncopep: Consultancy; Oncopep: Equity Ownership; Oncopep: Oncopep Patents & Royalties. Richardson:Celgene, Millenium, Johnson&Johnson: Membership on an entity’s Board of Directors or advisory committees. Raje:Amgen, Novartis, Onyx, Celgene, Millenium: Consultancy; Eli Lilly, Acetylon: Research Funding.

The emerging role of consolidation and maintenance therapy for transplant-eligible multiple myeloma patients

Multiple myeloma (MM) is an incurable malignant cancer of plasma cell origin. It is highly treatable with glucocorticoids, alkylating drugs, and novel agents including the proteasome inhibitors (bortezomib and carfilzomib) and the immunomodulatory drugs (IMiDs) thalidomide, lenalidomide and pomalidomide. Induction regimens incorporating the newer agents have resulted in deeper responses that have translated into prolonged response and survival for transplant eligible and transplant-ineligible MM patients. For the transplant-eligible patient, the current approach to those patients requiring therapy is induction, hematopoietic stem cell (HSC) collection, autologous HSC transplant (AHSCT) which may be followed by consolidation. Maintenance therapies with bortezomib or lenalidomide prolong response and appear to improve overall survival. For very high risk patients, allogeneic (alloHSCT) is an alternative therapy that may improve survival for selected patients. Incorporation of new therapies in combination with existing agents should lead increased response and improved survival of the MM patient with the ultimate goal of development of curative approaches for this disease.

Efficacy and Safety Of Melphalan and Prednisone In Combination With Thalidomide, Bortezomib Or Lenalidomide In Newly Diagnosed Transplant-Ineligible Multiple Myeloma Patients: A Single Center Experience

BackgroundThe introduction of new agents has substantially changed the management of patients with multiple myeloma (MM). PATIENTS AND METHODS: We evaluated retrospectively 69 symptomatic newly diagnosed transplant-ineligible MM patients treated at our Institute, between 2004 and 2012, with Melphalan and Prednisone (MP) plus Thalidomide (MPT; 23 patients) or plus Bortezomib (MPV; 30 patients) or plus Lenalidomide (MPR; 16 patients). There were 37 men and 32 woman, median age was 73 years (range 65-84) with 20 patients >75 years, 19 (27.5%) were in stage III according to ISS, 12 (17%) had renal failure (creatinine >1.5 mg/dl at baseline), 7 (10%) an underlying diabetes mellitus and 36 (52%) a cardiovascular disease. Melphalan was given at 9 mg/m2 and Prednisone at 60 mg/m2 orally on days 1-4; Bortezomib at 1.3 mg/m2 intravenously on days 1, 4, 8, 11, 22, 25, 29, 32 for the first 4 cycles and thereafter on days 1, 8, 15, 22; Lenalidomide at 10 mg on days 1-21 and Thalidomide 100 mg/daily were administered orally. All patients received antibacterial prophylaxis; thromboprophylaxis and antiviral prophylaxis were administered to patients treated with IMIDs and Bortezomib, respectively. AimsTo evaluate the safety and efficacy within the MPT-, MPV- and MPR-treated groups. ResultsThe overall response rates ( ≥ partial response), according to the IMWG criteria, were 20/23 (87%) in the MPT group, 26/30 (87%) in the MPV group, 11/16 (68%) in the MPR group (including 3, 9, 2 very good partial response and 2, 3, 2 complete response/near complete response, respectively). The median PFS was 29 months (95% CI: 18-NA months) for patients who received MPT, 24 months (95% CI: 20-32 months) with MPV and 21.5 months (95% CI: 17-NA months) with MPR, with no significant differences between the three regimens. Among the 69 patients, the overall grade 3-4 hematologic and non-hematologic toxicities were 36% and 43%, respectively. The most common non-hematologic toxicities included all grades of peripheral neuropathy (14% with MPV, 7.2% with MPT and none with MPR), grade 3-4 infections (7.2% with MPV, 4.3% with MPT and 2.9 with MPR) and grade 3-4 cardiovascular disease (4.3% with MPT, 1.4% with MPV and none with MPR). With the use of thromboprophylaxis in all IMID-treated patients, we observed only one deep vein thrombosis in one patient treated with MPT. ConclusionsMPT, MPV and MPR are highly active and well tolerated regimens for previously untreated MM patients. The rates of treatment-associated thrombocytopenia and neutropenia were similar between the 3 different regimens and proved transient, predictable and manageable; few patients required supportive care. The results obtained using MP plus one of the recently developed drugs confirm that MPT, MPV and MPR should be considered the standard of care in the frontline treatment of newly diagnosed transplant-ineligible MM patients. Disclosures:Petrucci:Janssen and Celgene: Honoraria; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees.

The Diagnostic and Prognostic Utility of 18F-FDG PET/CT in Transplant Ineligible Multiple Myeloma Patients Receiving Novel Agents

BackgroundThe value of 18F-fluorodeoxyglucose positron emission tomography integrated with computed tomography (FDG-PET/CT) in diagnosis and monitoring of multiple myeloma (MM) has been demonstrated predominantly in younger patients who are eligible for autologous stem cell transplantation. However, a majority of the MM patients are known to be transplant ineligible because of advanced age, comorbidity and/or frailness. Therefore, to evaluate the diagnostic and prognostic value of FDG- PET/CT in such patients is expected to contribute the physicians to design the more adequate personalized therapies. Patients and MethodWe reviewed the medical records of previously untreated symptomatic MM patients who were diagnosed at Osaka Saiseikai Nakatsu Hospital between February 2008 and June 2013. In this retrospective study, transplant ineligible patients who received FDG-PET/CT examination prior to the initial treatment were evaluated. A total of 48 patients (17 males and 31 females, median age of 71 years (range 47-91) were evaluable. IgG, IgA, BJP and non-secretory types were 35 (73%), 10 (21%), 1 (2%), and 2 (4%), respectively. The ISS stage 1, 2 and 3 comprised 15 (31%), 17 (35%) and 16 (33%), respectively. Closely after the FDG-PET/CT, all patients underwent the treatment including novel agents (bortezomib or lenalidomide). The results from FDG-PET/CT were evaluated and categorized by a team of experienced radiologists into three groups just according to the criteria proposed by Zamangni et.al. (Blood 2011;118:5989-5995): focal lesion (FL), diffuse lesion (DL), and extramedullary disease (EMD). And standard uptake value maximum (SUV max) was recorded. Imaging valuables of FDG-PET/CT were analyzed for association with other baseline parameters including types of serum or urinary M protein, serum levels of albumin (Alb), beta-2-microglobulin (B2M), C-reactive protein (CRP), lactate dehydrogenase (LDH), and CD19, 20 and 56 expressions in CD138 positive plasma cells in bone marrow. Furthermore, valuable combination of these parameters in predicting a clinical outcome of the patients was screened. A Kruskal-Wallis or Mann-Whitney U test was used to compare imaging variables in relation to baseline parameters. Kaplan-Meier analysis was used to estimate overall survival (OS). Univariate and multivariate analyses of prognostic factors were carried out using logistic regression. ResultsOf the 48 patients, 17% of the patients had a negative PET/CT scan before the treatments, 24% had 1 to 3 FLs, 59% had either DL or more than 3 FLs, and 9% had EMD. The serum levels of CRP, LDH, B2M, and Alb were 1.9 mg/L, 174 IU/L, 3.8 mg/L, and 37 g/L, respectively. A median SUV max was 3.7 in the all patients. As shown in Table 1, a median serum B2M level was significantly higher in patients with >3 FLs and/or DLs compared with 1-3 FLs (p=.014). A median SUV max significantly higher in patients with >3 FLs and/or DLs or EMD (p=.001). In addition, SUV max was significantly higher in patient with CD56-low, compared with CD56-high myeloma cells (8.0 vs. 3.3 p=.017). In a median follow up period of 20 months (range 2-67), 45, 10 and 45% of the patients received the treatments with lenalidommide, bortezomib and both, respectively. Estimated median OS of the all patients was 40 months (range 33-48). The ISS staging at the baseline did not significantly affect the OS. On univariate analysis, low serum Alb (Alb <35g/L) and high SUV max (SUV max>3.7) were unfavorable prognostic factors (p=.042 and p=.062, respectively). On multivariate analysis, the results from FDG-PET/CT did not significantly correlated with the OS. Interestingly, however, the OS for patients satisfying with both low Alb and high SUV max was significantly shorter than those with the other patients. (median 19 month vs. 45 month p=.029) (Figure1). [Display omitted] Table1The correlation between FDG-PET/CT category and B2M or SUV max.1-3 FLs>3 FLs and/or DLsEMDB2M (mg/L)2.54.4*2.6*p=.014SUV max2.04.7*12.3**p=.001 ConclusionThis study demonstrated that FDG-PET/CT at baseline can exactly evaluate tumor spread and variability. Furthermore, FDG-PET/CT in combination with other parameter was expected to provide additional information on making treatment strategy in transplant-ineligible MM patients receiving novel agents. Disclosures:No relevant conflicts of interest to declare.

Incorporating Novel Agents in the Management of Elderly Myeloma Patients

In recent years, the treatment of multiple myeloma has undergone significant changes. The availability of novel agents bortezomib, thalidomide and lenalidomide considerably improved the outcome of patients. The advantages related to the use of novel agents have been shown in various studies in patients eligible and ineligible for transplant. In elderly patients, novel agents have also revolutionized the treatment paradigm and have replaced the traditional melphalan-prednisone regimen. A sequential approach consisting of an induction regimen associated with a high rate of complete response, followed by consolidation/maintenance therapy, induces a profound cytoreduction and delays relapse, thus improving survival. Patients older than 75 years or who are otherwise vulnerable are more susceptible to adverse events. In this setting, less toxic regimens and appropriate dose-reductions should be adopted. This article provides an overview of the main trials for transplant-ineligible multiple myeloma patients. Recommendations on how to manage unfit patients and treatment-related toxicities are also provided.

The Cost-Effectiveness of Initial Treatment of Multiple Myeloma in the U.S. With Bortezomib Plus Melphalan and Prednisone Versus Thalidomide Plus Melphalan and Prednisone or Lenalidomide Plus Melphalan and Prednisone With Continuous Lenalidomide Maintenance Treatment

The outlook for transplant-ineligible multiple myeloma patients has improved enormously over recent years with the incorporation of new agents into standard regimens. Novel regimens combine melphalan and prednisone (MP) with bortezomib (VMP), with thalidomide (MPT), and with lenalidomide with (MPR-R) and without (MPR) lenalidomide maintenance. The efficacy, safety, and cost-effectiveness of these regimens have not yet been compared; therefore, we conducted a pharmacoeconomic analysis using data from randomized controlled trials versus MP. Using a Markov model developed from a U.S. payer's perspective, we compared VMP with MPT and MPR-R over a lifetime horizon. MPT and MPR-R were chosen because, like VMP, they are superior to MP in response and outcomes. Data from the Velcade as Initial Standard Therapy in Multiple Myeloma (VISTA; VMP), Intergroupe Francophone du Myelome (IFM) 99-06 (MPT), and MM-015 (MPR-R) trials were used. The IFM 99-06 study was selected because of the superior activity in this study compared with other MPT studies. Using patient-level (VMP) and published (MPT, MPR-R) data, we estimated the health-state transition and adverse event probabilities for each regimen, related costs, and state-specific utility estimates. Costs (in 2010 U.S. dollars) and health outcomes were discounted at 3%. Discounted lifetime direct medical costs were lowest with VMP at $119,102. MPT cost $142,452 whereas MPR-R cost $248,358. Incremental cost-effectiveness ratio calculations projected that VMP would confer cost savings and better health outcomes relative to MPT and MPR-R. We conclude that VMP is highly likely to be cost-effective compared with MP, MPT, and MPR-R.

Efficacy and Safety of Three Bortezomib-Based Combinations in Elderly, Newly Diagnosed Multiple Myeloma Patients: Results From All Randomized Patients in the Community-Based, Phase 3b UPFRONT Study

Abstract 478 Background:The US community-based, phase 3b randomized, open-label, multicenter UPFRONT trial compares the efficacy and safety of three bortezomib (VELCADE®, Vc)-based regimens, VcD (Vc-dexamethasone), VcTD (Vc-thalidomide-dexamethasone), and VcMP (Vc-melphalan-prednisone), followed by weekly Vc maintenance, in elderly, newly diagnosed, transplant-ineligible multiple myeloma (MM) patients. This is the first phase 3 study of VcD and VcTD in this patient population. Methods:Patients with symptomatic, measurable MM were randomized (1:1:1) to receive 49 weeks of therapy: 24 weeks (eight 21-day cycles) of induction with VcD, VcTD, or VcMP (VcD: Vc 1.3 mg/m2, days 1, 4, 8, 11; D 20 mg, days 1, 2, 4, 5, 8, 9, 11, 12 [cycles 1–4]), days 1, 2, 4, 5 [cycles 5–8]); VcTD: Vc as before; T 100 mg/day, days 1–21; D as before); VcMP: Vc as before; M 9 mg/m2 and P 60 mg/m2, days 1–4, every other cycle), followed by 25 weeks (five 35-day cycles) of maintenance with weekly Vc 1.6 mg/m2, days 1, 8, 15, 22. Patients in the VcTD arm received concomitant prophylaxis with aspirin, full-dose warfarin, or low-molecular weight heparin unless medically contraindicated. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall response rate (ORR), complete response (CR)/near CR (nCR) and very good partial response (VGPR) rates, overall survival (OS), and safety. Best confirmed responses were assessed by investigators per modified International Myeloma Working Group (IMWG) criteria. Adverse events (AEs) were graded by NCI-CTCAE v3.0. PFS and OS were estimated by Kaplan–Meier methodology. For the first time, we report results from the entire cohort of 502 randomized patients (VcD, n=168; VcTD, n=167; VcMP, n=167), who completed up to a maximum of 13 cycles of treatment. Results:Patients in the VcD, VcTD, and VcMP arms had a median age of 74.5, 73.0, and 72.0 years, respectively, and 71%, 62%, and 72% had ISS stage II/III disease. Patients received a median of 8 (VcD), 6 (VcTD), and 7 (VcMP) treatment cycles; 50%, 38%, and 42% of patients, respectively, received Vc maintenance. Response and safety data are summarized in the table. All three Vc-based induction regimens exhibited substantial activity, with ORR of 73% (VcD), 80% (VcTD), and 69% (VcMP) during the treatment period. After a median follow-up of 21.8 months, no significant difference in PFS was observed between the treatment arms; median PFS was 13.8 months (VcD), 14.7 months (VcTD), and 17.3 months (VcMP), respectively (Figure). 1-year OS estimates were 87.4% (VcD), 86.1% (VcTD), and 88.9% (VcMP). Rates of grade ≥3 AEs, serious AEs (SAEs), and discontinuations due to AEs during the treatment period were highest for the VcTD arm. The most common grade ≥3 AEs across all three arms during the treatment period were neuropathy peripheral (23%), fatigue (10%), and diarrhea (9%). Grade ≥3 pneumonia was reported in 10% (VcD), 6% (VcTD), and 6% (VcMP) of patients. AEs of deep vein thrombosis/pulmonary embolism were reported in 8% (VcD), 7% (VcTD), and 2% (VcMP) of patients. Compared with rates during induction, Vc maintenance produced little additional toxicity; across all three treatment arms, only 5% of patients experienced grade ≥3 peripheral neuropathy during cycles 9–13. One second primary malignancy (lung neoplasm) was reported in the VcMP arm. Conclusions:VcD, VcTD, and VcMP induction followed by weekly Vc maintenance produced similar activity in elderly, newly diagnosed, transplant-ineligible MM patients. Patients in the VcD doublet arm appear to have similar long-term outcomes to patients in the VcTD and VcMP triplet arms.VcDVcTDVcMPBest confirmed response rates during the treatment periodResponse, %n=146n=133n=144ORR (≥PR)738069CR/nCR*304033VGPR7118PR362929Stable disease15215Progressive disease2<13Not evaluable101712Safety profile during induction (I; cycles 1–8) and during maintenance (M; cycles 9–13)†I (n=165)M (n=82)I (n=158)M (n=60)I (n=163)M (n=69)AE, %Grade ≥3 AEs749848823SAEs48115312479Discontinuation of all study drugs due to AEs2411353309Deaths (within 30 days of last dose)506050*nCR includes patients IF+ as well as patients IF- but in whom confirmatory BM biopsy was not performed;†The M column represents first onset of an AE during maintenance [Display omitted] Disclosures:Niesvizky:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Research Funding. Flinn:Millennium Pharmaceuticals, Inc.: Research Funding. Rifkin:Celgene: Speakers Bureau; Amgen: Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees; Millennium Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Charu:GSK: Research Funding; Celgene: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Bristol-Myers Squibb: Equity Ownership; Pfizer: Equity Ownership. Neuwirth:Millennium Pharmaceuticals, Inc.: Employment. Corzo:Millennium Pharmaceuticals, Inc.: Employment.

Patient-Reported Quality of Life (QoL) in Elderly, Newly Diagnosed Multiple Myeloma (MM) Patients Receiving Bortezomib-Based Combinations: Results From All Randomized Patients in the Community-Based, Phase 3b UPFRONT Study

Abstract 1864 Background: In addition to determining the efficacy and safety of different treatment options for MM, the impact of treatment and associated toxicities on patient-reported QoL should be evaluated. The US community-based phase 3b UPFRONT study compares the efficacy and safety of three bortezomib (VELCADE®, Vc)-based regimens, Vc-dexamethasone (VcD), Vc-thalidomide-dexamethasone (VcTD), and Vc-melphalan-prednisone (VcMP), followed by weekly Vc maintenance, in elderly, newly diagnosed, transplant-ineligible MM patients. Updated efficacy and safety data are reported elsewhere at this meeting; here we present patient-reported QoL results – a secondary endpoint of the trial – from all 502 randomized patients, who received up to a maximum of 13 treatment cycles. Methods: Patients with symptomatic MM were randomized (1:1:1) to receive eight 21-day cycles of VcD (Vc 1.3 mg/m2, days 1, 4, 8, 11; D 20 mg, days 1, 2, 4, 5, 8, 9, 11, 12 [cycles 1–4]), days 1, 2, 4, 5 [cycles 5–8]), VcTD (Vc as before; T 100 mg/day, days 1–21; D as before), or VcMP (Vc as before; M 9 mg/m2, and P 60 mg/m2, days 1–4, every other cycle) induction, followed by five 35-day cycles of maintenance with Vc 1.6 mg/m2, days 1, 8, 15, 22. QoL was assessed using the EORTC QLQ-C30 questionnaire, which includes global health status, physical, role, cognitive, emotional, and social functioning, and symptom scales of fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties. Global health status scores combine overall health and QoL scores, with higher scores reflecting better health status. Questionnaires were completed prior to dosing on day 1 of cycle 1 (baseline), prior to dosing on day 1 of every odd-numbered cycle, at the end-of-treatment visit, and every 12 weeks until progressive disease. Patient-reported QoL scores presented herein represent data collected within 1 year of randomization regardless of discontinuation status; for patients who died, missing assessments were assigned the worst possible score of 0. A linear mixed effect model was used to assess QoL changes over time, both within and between treatment arms. Sensitivity analyses were conducted to test the robustness of the primary analysis. Results: Patient baseline characteristics were well balanced across the VcD (n=168), VcTD (n=167), and VcMP (n=167) arms as reported previously (Niesvizky et al, EHA 2011). Median age was 74.5 (VcD), 73.0 (VcTD), and 72.0 (VcMP) years, and 71%, 62%, and 72% of patients had ISS stage II/III disease. QoL assessments were available at baseline and ≥1 post-baseline time point for 78% (VcD), 69% (VcTD), and 78% (VcMP) of patients. Observed data showed a downward trend in mean global health status score until cycle 7 (VcD, VcMP) or 9 (VcTD), followed by a trend to stabilizing/improving score thereafter (Figure). Symptom scores changed very little during induction in all arms, except for nausea/vomiting and diarrhea, with moderate improvements seen during maintenance. After fitting observed data with a linear mixed effect model, a significant decrease in mean global health status score from baseline to cycle 7 (induction period) was evident in all arms (VcD, p=0.0127; VcTD, p Conclusions: The observed data, linear mixed model estimates, and sensitivity analyses all show a common trend to a transient decrease in QoL during VcD, VcTD, and VcMP induction followed by a subsequent trend to improvement/stabilization in QoL during single-agent Vc maintenance. The trend to decreasing QoL seen during Vc-based induction may reflect the onset of treatment-related toxicities (particularly for VcTD, which was associated with somewhat higher toxicity rates). Post-induction improvements/stabilization in QoL may reflect the beneficial impact of achieving a response and the limited toxicity profile associated with weekly Vc maintenance. Disclosures: Niesvizky:Celgene: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Research Funding. Flinn:Millennium Pharmaceuticals, Inc.: Research Funding. Rifkin:Onyx: Membership on an entity9s Board of Directors or advisory committees; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Millennium Pharmaceuticals, Inc.: Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau. Charu:Pfizer: Equity Ownership; Bristol-Myers Squibb: Equity Ownership; Roche: Research Funding; GSK: Research Funding; Celgene: Research Funding; Novartis: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Amgen: Equity Ownership, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding. Neuwirth:Millennium Pharmaceuticals, Inc.: Employment. Huang:Millennium Pharmaceuticals, Inc: Employment. Choi:Millennium Pharmaceuticals, Inc.: Employment. Corzo:Millennium Pharmaceuticals, Inc.: Employment.

Is the Low-Thalidomide Dose MPT Regimen Beneficial?

Is the Low-Thalidomide Dose MPT Regimen Beneficial?