Eligible Multiple Myeloma Patients Research Articles

Treatment in Transplant Eligible Multiple Myeloma Patients in Macedonia: Development of Cost-Effectiveness Analysis

Treatment in Transplant Eligible Multiple Myeloma Patients in Macedonia: Development of Cost-Effectiveness Analysis

Minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) in newly diagnosed transplant eligible multiple myeloma (MM) patients: Results from the EMN02/HO95 phase 3 trial.

8011 Background: MRD detection is a sensitive tool to measure response in MM. We assessed MRD by MFC in newly diagnosed MM patients (pts) enrolled in the EMN02/HO95 phase 3 trial. Methods: Pts were ≤65 years old and received Bortezomib-Cyclophosphamide-Dexamethasone (VCD) induction, intensification with Bortezomib-Melphalan-Prednisone (VMP) vs High-Dose-Melphalan (HDM) followed by stem cell transplant, consolidation with Bortezomib-Lenalidomide-Dexamethasone (VRD) vs no consolidation, and Lenalidomide maintenance. MRD analysis was performed in pts achieving at least a very good partial response (VGPR) before starting maintenance (after HDM, VMP or VRD) and during maintenance every 6-12 months; samples were centralized to 3 European labs. MFC was performed on bone marrow according to Euroflow-based methods (8 colors, 2 tubes) with a sensitivity of 10-5. Quality checks were performed to compare sensitivity and to show correlation between protocols (Hofste op Bruinink D ASH 2016 abstract 2072). Results: 316 pts were evaluable before maintenance: median age was 57 years, 18% (57/316) pts had ISS III and 22% (70/316) had high risk cytogenetic (HR-C) defined as having at least one among del17, t(4;14) or t(14;16); 63% (199/316) had received HDM and 37% (117/316) VMP; thereafter 51% (160/316) had received VRD. 76% (239/316) were MRD negative (MRD-) of whom 64% (153/239) received HDM vs 36% (86/239) VMP, with a median follow-up time of 30 months from MRD enrolment. 3-year PFS was 50% in MRD positive (MRD+) vs 77% in MRD- pts (HR: 2.87, p < 0.001). Subgroup analyses were performed to evaluate the risk factors for MRD+ according to baseline characteristics and therapies: HR-C was the most important risk factor (HR 9.87, interaction-p = 0.001). Finally, 48% of MRD+ pts at pre-maintenance who had a second MRD evaluation after at least 1 year of lenalidomide became MRD-. Conclusions: MRD by MFC is a strong prognostic factor in MM pts receiving intensification with novel agents or transplant; lenalidomide maintenance further improved depth of response; HR-C is the most important prognostic factor in MRD+ pts. Clinical trial information: NCT01208766.

Efficacy and safety of carfilzomib regimens in multiple myeloma patients relapsing after autologous stem cell transplant: ASPIRE and ENDEAVOR outcomes

Autologous stem cell transplantation (ASCT) is a standard treatment for eligible multiple myeloma (MM) patients, but many patients will relapse after ASCT and require subsequent therapy. The proteasome inhibitor carfilzomib is approved for relapsed or refractory MM (RRMM). In phase 3 trials, carfilzomib-based regimens (ASPIRE, carfilzomib–lenalidomide–dexamethasone; ENDEAVOR, carfilzomib–dexamethasone) demonstrated superior progression-free survival (PFS) compared with standard therapies for RRMM (ASPIRE: lenalidomide–dexamethasone; ENDEAVOR, bortezomib–dexamethasone). This subgroup analysis of ASPIRE and ENDEAVOR evaluated outcomes according to prior ASCT status. In total, 446 patients in ASPIRE and 538 in ENDEAVOR had prior ASCT. Median PFS was longer for carfilzomib-based regimens vs non-carfilzomib-based regimens for patients with prior ASCT (ASPIRE: 26.3 vs 17.8 months (hazard ratio (HR)=0.68); ENDEAVOR: not estimable vs 10.2 months (HR=0.61)), those with one prior line of therapy that included ASCT (ASPIRE: 29.7 vs 17.8 months (HR=0.70); ENDEAVOR: not estimable vs 11.2 months (HR=0.46)), and those without prior ASCT (ASPIRE: 26.4 vs 16.6 months (HR=0.76); ENDEAVOR: 17.7 vs 8.5 months (HR=0.43)). Overall response rates also favored the carfilzomib-based regimens. No new safety signals were detected. This analysis suggests that carfilzomib-based treatment may lead to improvement in PFS and response rates regardless of prior transplant status. Further evaluation is warranted.

Efficacy and Safety of Weekly Bortezomib Containing VMP Followed By Bortezomib Maintenance Therapy in Unfit or Frail Multiple Myeloma Patients

Abstract Background: According to VISTA study, the prognosis of elderly multiple myeloma (MM) patients has been improved with VMP therapy. However, intensive chemotherapy has induced severe adverse events (AEs), resulting in highly discontinued rate, especially often seen in unfit or frail patients. Several studies have demonstrated the potent of weekly bortezomib administration in induction therapy (GIMEMA, GEM2005MAS65), and maintenance therapy with bortezomib. Based on these fact, we designed phase 2 clinical study, BoRtezomib-based Optimized therapy Aiming Disease control in Japan (BROAD-J study), based on a weekly VMP as induction therapy followed by maintenance therapy with bortezomib (Bor-MT) with every two weeks administration for newly-diagnosed (ND) symptomatic non-transplant eligible MM patients. (UMIN 00007335) Method: From August 2011 to June 2016, according to the International Myeloma Working Group (IMWG) criteria, 87 patients older than 65 years with symptomatic MM were eligible for this trial (Table 1). The primary objectives were included maximum response and time to progression duration. Secondary objective was the continued treatment duration and adverse event rate. The induction phase consisted of VMP treatment: Melpharan: on days 1-4 (6 mg/m2), every 35-day cycle; prednisolone: on days 1-4 (40mg/d, every 35-day cycle; Bortezomib: 1.3mg/m2, d1, 8, 15, 22 every 35-day cycle. After 9 cycles of VMP therapy, the maintenance therapy starts. The maintenance phase was consisted of twice a month bortezomib administration (1.3 mg/m2) without dexamethasone until progressive disease. Dose reductions of bortezomib were allowed according to instructorfs recommendation. Patients could receive supportive therapy including bisphosphonates and transfusions as necessary. AEs were graded according to NCI-CTCAE v4.0. Response was assessed prior to every treatment cycle. Response categories were based on the International Myeloma Working Group uniform response criteria. Results: Mean age was 75 years (66-88), sex ratio was 44:43 (M: F), and ISS stage was I 12%, II 43%, III 43%. High risk cytogenetics abnormalities (i.e. del17p, t(14;16)) were observed in 13 patients (15%). Overall response rate was 87% and complete response was obtained in 22 patients (25%) (Table 1). Median progression free survival (PFS) was 36 months (Figure 1a) and median overall survival was 57 months (Figure 1b). Median PFS (Kaplan-Meier estimate) was significantly higher with patients who obtained CR or VGPR than PR or SD (P Discussion: This trial reveals that VMP regimen with weekly bortezomib administration is effective and tolerablefor unfit or frail elderly MM patients. In addition, maintenance therapy of twice a month bortezomib administration was effective in patients who obtained VGPR or more better. These results are no way inferior to results of VISTA trial. However, high R-ISS stage patients or poor treatment responders did not obtain the benefit of this setting, so, another setting with anti-myeloma antibody (i.e. elotuzumab or daratumumab) may be warranted in the future for such patients. Conclusion: BROAD-J study is conducted to yield the possibility of a careful treatment toward at least PR state and the efficacy of VMP followed by bortezomib maintenance in unfit or frail MM patients. The excellent results we demonstrated such as a good OS, PFS, and a low incidence of AEs might be suggested a superiority of this strategy. Download : Download high-res image (64KB) Download : Download full-size image Disclosures Tokuhira: Bristol Myers Squibb Co., Ltd: Honoraria; Eizai Co., Ltd: Honoraria; Pfizer Co., Ltd: Honoraria.

Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to Lenalidomide and Dexamethasone (LD) for the Treatment of Non-Transplant Eligible MM

Introduction : Cyclophosphamide, bortezomib and Dexamethasone (CyBorD) has become the standard frontline approach for the treatment of multiple myeloma (MM) in many centers across Canada. In the non-transplant eligible setting, recently a randomized controlled trial reported on the impact of Lenalidomide and Dexamethasone (LD), showing that this doublet-therapy is a feasible and efficacious combination. Based on the above-mentioned success of the LD combination, we aimed to compare the effect of CyBorD and LD for the treatment of non-transplant eligible MM (NTE) patients in the Alberta Myeloma and Dysproteinemia Program (AMDP). Patients and Methods : The primary objective was to assess ORR and PFS for NTE MM patients treated with CyBorD and LD. The recommended CyBorD regimen was as follows: bortezomib 1.3-1.5 mg/m2 SC or IV days 1, 8, 15 of a 28 day cycle (as of August, 2013 we adopted the a strategy whereby bortezomib can also be given on day 22), cyclophosphamide 300 mg/m2 PO days 1, 8, 15 and 22 and dexamethasone 20-40 mg PO days 1, 8, 15 and 22 with an aim to deliver a minimum of 9 cycles of treatment. LD was given at 25 mg days 1-21 of a 28-day cycle with Dexamethasone 20-40 mg PO days 1, 8, 15 and 22. Dose adjustments were at the discretion of the treating physician. Two-sided Fisher exact test was used to test for differences between categorical variables. A p value of <0.05 was considered significant and survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Results: Ninety-one patients have received CyBorD and 56 have received LD. Clinical characteristics are shown in Table 1 . At the time of analysis, 64 and 32 patients in the CyBorD and LD are alive of which 10 and 11, respectively, have progressed, ORR and VGPR rates were 85.7% and 56% for patients treated with CyBorD, and 83.9% and 64% for LD respectively (p=0.3). Estimated median OS was 40 months for CyBorD compared to 66 months for LD (p=0.156). In addition, median PFS was longer for LD patients compared to CyBorD (26 months vs 16.4 months, p=0.018). The rate of treatment discontinuation was similar between both groups (8.7% vs 10%, p=0.3). In Conclusion: CyBorD and LD appeared to be effective treatment options for NTE myeloma patients with similar response rates. Recognizing the limitations of a retrospective series, it is interesting to note a longer PFS and a trend towards better PFS in the LD group, however, longer follow-up and prospective validation is still required. | Characteristic | CyBorD, n=91 | LD, n=56 | P value | | ---------------------------------------------------------------------------------------- | ------------------------------------------------- | ------------------------------------------------ | ------- | | Age (median) | 73.9 | 73.6 | 0.2 | | Gender Male Female | 57 (62.6%) 34 (37.4%) | 34 (60.7%) 22 (39.3%) | 0.8 | | B2microglobulin (µmol/L) | 4.9 | 4.89 | 0.4 | | Albumin (g/L) | 35 | 36 | 0.7 | | Stage I Stage II Stage III | 17.7% 35.4% 46.9% | 23.5% 37.2% 39.3% | 0.6 | | BMPC (%) | 32 | 37.5 | 0.6 | | Heavy chain: IgG IgA FLC only IgD IgM Biclonal | 50 10 18 1 1 3 | 26 17 9 0 1 0 | 0.068 | | Response rate ORR CR/nCR VGPR PR | 85.7% 23% 31.8% 30.7 | 83.9% 28% 37.5% 17.8% | 0.3 | * Ab : BMPC: Bone marrow plasma cell Table 1. Clinical Characteristics ![Figure 1.][1] Figure 1. Overall Survival according to treatment regimen ![Figure 2.][1] Figure 2. Progression-Free survival according to treatment regimen Disclosures Jimenez-Zepeda: Celgene: Honoraria; Amgen: Honoraria; JJ Celgene: Honoraria, Research Funding; Amgen: Honoraria. Sandhu: Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Duggan: Celgene: Honoraria; Jansen: Honoraria. Neri: Celgene: Research Funding. Bahlis: Johnson & Johnson: Speakers Bureau; Johnson & Johnson: Research Funding; Amgen: Consultancy; Johnson & Johnson: Consultancy; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. [1]: pending:yes

Towards Response-Adaptive Changes in Induction Therapy to Improve Survival Outcomes in Transplant Eligible Multiple Myeloma Patients

Towards Response-Adaptive Changes in Induction Therapy to Improve Survival Outcomes in Transplant Eligible Multiple Myeloma Patients

The Cost Impact of Lenalidomide for Newly Diagnosed Multiple Myeloma in the EU5.

IntroductionLenalidomide is an active agent that was approved for use in the EU in 2015 as a first-line therapy for previously untreated, non-transplant eligible multiple myeloma patients. Our objective was to assess the cost impact of lenalidomide when selected as a first-line treatment for transplant-ineligible patients in France, Germany, Italy, Spain, and the United Kingdom (EU5).MethodsWe developed a cost-impact model of the total costs associated with newly diagnosed multiple myeloma over 5 years in the EU5 based on treatment duration and time to progression (TTP) (taken from trial data). We compared a baseline scenario (of current lenalidomide uptake) with two alternative future scenarios. Future Scenario A used an increased uptake of first-line lenalidomide: up to 50% in Year 5. Future Scenario B was similar to the baseline, but included a 20% increased uptake of the triple therapy regimen, carfilzomib, lenalidomide, and dexamethasone (KRd) at second line.ResultsCompared to alternative first-line care pathways, lenalidomide provides a time to progression advantage of up to 5.1 months. In the baseline scenario, the costs per patient were €40,692 in Year 1. Future Scenario A showed an additional expenditure of €867 per patient in Year 1, increasing to €3358 per patient by Year 5, a 2.1% and 8.2% increase from baseline, respectively. However, lenalidomide use was associated with a lower monthly hospitalisation per-patient cost (€813) compared with bortezomib (€1173) and thalidomide (€1532). Future Scenario B was associated with a 29% increase in cost.ConclusionsCompared to other first line therapies, lenalidomide delays time to progression resulting in associated savings across a patient’s treatment pathway and overall is likely to result in a limited impact on budget. Lenalidomide should, therefore, be considered as a first treatment option for multiple myeloma patients ineligible for transplant.FundingCelgene Ltd.

Prospective Evaluation of 18F-FDG PET/CT As Predictor of Prognosis in Newly Diagnosed Transplant Eligible Multiple Myeloma (MM) Patients: Results from the Imaging Sus-Study of the EMN02/HO95 MM Randomized Phase III Trial

F-18-fluorodeoxyglucose positron emission tomography integrated with computed tomography (FDG-PET/CT) enables to detect with relatively high sensitivity and specificity myeloma bone disease and extramedullary sites of metabolically active clonal plasma cells. FDG-PET/CT has also been used to assess and monitor the metabolic response to therapy and to predict the prognosis. One of the major limitation of PET/CT is the lack of standardized image criteria and of inter-observer reproducibility in interpreting the results.Aim of the present sub-study was to prospectively evaluate FDG-PET/CT at diagnosis, after 4 cycles of induction therapy and prior to maintenance therapy in a sub-group of patients enrolled into EMN02/HO95 MM international phase III trial. In particular, the two primary end-points were firstly to assess the prognostic significance of PET/CT at diagnosis and after therapy and secondly to standardize PET/CT evaluation by centralized imaging and revision and definition of criteria for interpretation.Seven hundred and 18 patients with newly diagnosed transplant-eligible symptomatic MM have been prospectively randomized in Italy from February 2011 through April 2014 to receive 4 cycles of bortezomib-melphalan-prednisone (VMP) vs high-dose melphalan and single or double autologous stem cell transplantation (ASCT) as intensification following induction with bortezomib-cyclophosphamide-dexamethasone (VCD). Consolidation therapy with bortezomib-lenalidomide-dexamethasone vs no consolidation was planned after VMP or ASCT(s), followed by lenalidomide maintenance until progression or toxicity. One hundred and three patients were included in the PET/CT imaging sub-study, and followed for a median of 24 months. By study design, PET/CT was performed and analysed in each of the 8 participating centres at baseline, after induction therapy and prior to the start of maintenance (EOT). Each PET scan was a posteriori re-interpreted in a blinded independent central review process, managed by WIDEN®, by a panel of 5 expert nuclear medicine physicians. They described the following characteristics: bone marrow metabolic state (BM), number (Fx) and score (Fs) of focal PET positive lesions, osteolysis (Lx), presence and site of extramedullary disease (EM), and fractures(Fr), according to the IMPeTUs criteria (Nanni et al, EJNM 2015). Moreover, a global score (GS), from 1 to 5, was given to each patient, considering the highest score among BM, Fx, Fs and EM. Concordance among reviewers on different metrics was calculated using Krippendorf’s alpha (AK) coefficientBaseline characteristics of the patients were the following: median age 58 years, ISS and R-ISS stage III 15% and 10%, high-risk cytogenetics (t(4;14) ± del(17p) ±del (1p)±1q gain detected by FISH) 42%.At baseline, 78% of the patients had FLs, with a median SUVmax of 6.0. The percentages of PET positive patients for the different characteristics are summarized in table 1. The agreement among reviewer was good for BM (AK=0.49), Fx (AK=0.65), Fs (AK=0.62), Lx (AK=0.62) and EM (AK=0.40). Of all parameters, only Fx ≥ 4 was associated with worse PFS and OS (P = 0.06)Following 4 cycles of VCD, PET/CT remained positive in 59% of the patients, with a median SUVmax of 3.7. Of all parameters, only Fs ≥ 4 was predictive of worse OS (P= 0.05).Prior to maintenance therapy, PET/CT remained positive in 34% of the patients, with a median SUVmax of 3.4. Normal PET/CT findings before maintenance (66%) were associated with a significant improvement in PFS, in particular the following: presence of FLs (P=0.03), Fx ≥ 4 (P=0.001), Fs ≥2 (P=0.03), 3 (P=0.03) and 4 (P=0.006) and SUVmax ≥ 3.4 (p=0.002). GS was also predictive for PFS if ≥ 3 (P=0.033), 4 (P=0.0001) and 5 (P=0.004). The same parameters were also predictive for OS. The prognostic relevance of pre-maintenance PET/CT was retained across the randomization arm (VMP or ASCT), in terms of PFS and OS.In conclusion, PET/CT was confirmed to be a reliable predictor of outcome in newly diagnosed transplant eligible MM patients, whatever the treatment. Normalization of PET/CT before maintenance was associated with a significant improvement for PFS and OS. FDG-PET/CT is by now the preferred imaging technique for evaluating and monitoring response to therapy.Acknowledgments: this study was partially supported by a grant to Elena Zamagni from Fondazione del Monte di Bologna e Ravenna [Display omitted] DisclosuresGay:Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Membership on an entity's Board of Directors or advisory committees. Larocca:Bristol-Myers Squibb: Honoraria; Janssen-Cilag: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Sonneveld:Celgene: Other: Advisory board, Research Funding; Onyx: Other: Advisory board, Research Funding; Millennium: Other: Advisory board, Research Funding; Janssen-Cilag: Other: Advisory board, Research Funding. Cavo:Amgen: Honoraria; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria; Bristol-Myers Squibb: Honoraria.

Outcomes in Transplant Eligible Multiple Myeloma African American Patients Appear Similar to Caucasian Patients

Background: SEER Data from 1975-2008 show a stark disparity in the incidence of multiple myeloma (MM) in African Americans (AA) compared to Caucasians, with a 2-3 times higher incidence in AA. Differences in the incidence appear to be genetically driven, but remain poorly understood. Although AA patients appear to have a lower incidence of high risk cytogenetics [Greenberg G et al, Blood Cancer J 2015], their outcomes have not improved in the novel era therapy compared to Caucasian patients [Ailawahdi S et al, Blood Cancer J 2016]. Access to specialized disease-specific care (including access to a transplant center) due to socioeconomic status and lack of social support have been proposed as impediments to optimal care for AA MM patients. We prospectively examined newly diagnosed transplant eligible AA and Caucasian patients with MM at our institution to assess their transplant outcomes.Methods: The MM database was interrogated from March 2014-December 2015 for all autologous stem cell transplant (ASCT) eligible patients with MM. Clinical features, induction regimens, treatment responses and ASCT outcomes were compared between AA and Caucasian patients. Continuous variables were compared using nonparametric rank tests, while incidences and proportions were compared using Fisher's exact tests.Results: A total of 73 consecutive ASCT eligible MM patients were identified (32 AA, 41 Caucasian). There was no significant difference in sex distribution between the cohorts (p > 0.999). However, AA patients were significantly younger at the time of diagnosis with a median age of 56 years compared to a median age of 61 years in the Caucasian cohort (p = 0.008). Except for lower hemoglobin levels among AA patients, there were no statistically significant differences in any other clinical variable at diagnosis (lab features, serum LDH levels, ISS staging, IMWG risk stratification, cytogenetics, etc.) between the patient cohorts. Analysis of pre- and post- ASCT data showed similar response rates to induction therapy and outcomes with no statistically significant differences observed in pre-ASCT and post-ASCT depth of response (assessed by IMWG criteria) or 1-year progression free survival between the two cohorts.Conclusions: At our institution, AA patients with MM presented at a younger age than Caucasians. However, no significant differences in disease features were observed between the two groups at the time of initial presentation. A much higher proportion of AA MM patients (44%) underwent ASCT at our institution compared to other academic centers. Although longer follow-up is required, our data suggest that when AA patients with MM are provided similar access to care as Caucasian patients with MM, similar response rates to induction therapy and ASCT can be achieved. DisclosuresBhutani:Prothena: Research Funding; Bristol-Myers Squibb: Speakers Bureau; Takeda Oncology: Research Funding, Speakers Bureau; Onyx, an Amgen subsidiary: Speakers Bureau. Symanowski:Caris Life Sciences: Consultancy; Ra Pharma: Consultancy; Eli Lilly & Co: Consultancy; Endocyte: Consultancy. Avalos:Seattle Genetics: Membership on an entity’s Board of Directors or advisory committees. Usmani:Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pharmacyclics: Research Funding; Onyx: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Skyline: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Britsol-Myers Squibb: Consultancy, Research Funding; BioPharma: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Array: Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau; Novartis: Speakers Bureau.

The Efficacy and Safety of Weekly Bortezomib Containing VMP Followed By Bortezomib Maintenance Therapy in Unfit or Frail Multiple Myeloma Patients

Background: According to VISTA study, the prognosis of elderly multiple myeloma (MM) patients has been improved with VMP therapy. However, intensive chemotherapy has induced severe adverse events (AEs), resulting in highly discontinued rate, especially often seen in unfit or frail patients. Several studies have demonstrated the potent of weekly bortezomib administration in induction therapy (GIMEMA, GEM2005MAS65), and maintenance therapy with bortezomib. Based on these fact, we designed phase 2 clinical study, BoRtezomib-based Optimized therapy Aiming Disease control in Japan (BROAD-J study), based on a weekly VMP as induction therapy followed by maintenance therapy with bortezomib (Bor-MT) with every two weeks administration for newly-diagnosed (ND) symptomatic non-transplant eligible MM patients. (UMIN 00007335)Method: From August 2011 to June 2016, according to the International Myeloma Working Group (IMWG) criteria, 87 patients older than 65 years with symptomatic MM were eligible for this trial (Table 1). The primary objectives were included maximum response and time to progression duration. Secondary objective was the continued treatment duration and adverse event rate. The induction phase consisted of VMP treatment: Melpharan: on days 1-4 (6 mg/m2), every 35-day cycle; prednisolone: on days 1-4 (40mg/d, every 35-day cycle; Bortezomib: 1.3mg/m2, d1, 8, 15, 22 every 35-day cycle. After 9 cycles of VMP therapy, the maintenance therapy starts. The maintenance phase was consisted of twice a month bortezomib administration (1.3 mg/m2) without dexamethasone until progressive disease. Dose reductions of bortezomib were allowed according to instructorfs recommendation. Patients could receive supportive therapy including bisphosphonates and transfusions as necessary. AEs were graded according to NCI-CTCAE v4.0. Response was assessed prior to every treatment cycle. Response categories were based on the International Myeloma Working Group uniform response criteria.Results: Mean age was 75 years (66-88), sex ratio was 44:43 (M: F), and ISS stage was I 12%, II 43%, III 43%. High risk cytogenetics abnormalities (i.e. del17p, t(14;16)) were observed in 13 patients (15%). Overall response rate was 87% and complete response was obtained in 22 patients (25%) (Table 1). Median progression free survival (PFS) was 36 months (Figure 1a) and median overall survival was 57 months (Figure 1b). Median PFS (Kaplan-Meier estimate) was significantly higher with patients who obtained CR or VGPR than PR or SD (P<0.0001) (Figure 1c). Significantly higher ORR, rate of VGPR or better, and rate of CR or better were achieved in patients with revised ISS I stage, respectively. In induction phase, 32% of patients were suffered from greater than grade 3 AEs, whereas only 3% had grade 3 or 4 AEs in maintenance phase.Discussion: This trial reveals that VMP regimen with weekly bortezomib administration is effective and tolerablefor unfit or frail elderly MM patients. In addition, maintenance therapy of twice a month bortezomib administration was effective in patients who obtained VGPR or more better. These results are no way inferior to results of VISTA trial. However, high R-ISS stage patients or poor treatment responders did not obtain the benefit of this setting, so, another setting with anti-myeloma antibody (i.e. elotuzumab or daratumumab) may be warranted in the future for such patients.Conclusion: BROAD-J study is conducted to yield the possibility of a careful treatment toward at least PR state and the efficacy of VMP followed by bortezomib maintenance in unfit or frail MM patients. The excellent results we demonstrated such as a good OS, PFS, and a low incidence of AEs might be suggested a superiority of this strategy. [Display omitted] DisclosuresTokuhira:Bristol Myers Squibb Co., Ltd: Honoraria; Eizai Co., Ltd: Honoraria; Pfizer Co., Ltd: Honoraria.

Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to Bortezomib, Thalidomide and Dexamethasone (VTD) As Induction Therapy for the Treatment of Transplant Eligible Multiple Myeloma

Introduction: Cyclophosphamide, bortezomib and Dexamethasone (CyBorD) has become the standard frontline approach for the treatment of multiple myeloma (MM) in many centers across Canada. A recent study led by the IFM group showed that the triplet combination of bortezomib, thalidomide and dexamethasone is superior as an induction regimen compared to CyBorD for patients undergoing ASCT. Based on the above-mentioned, we aimed to compare the effect of CyBorD and VTD for the treatment of transplant eligible MM patients in 2 different centers from Canada and Spain. Patients and Methods: The primary objective was to assess ORR and ³VGPR rates after induction and at day-100 post-ASCT, as well as MRD assessed by flow cytometry. Two-sided Fisher exact test was used to test for differences between categorical variables. A p value of <0.05 was considered significant and survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Results: 101 patients have received CyBorD and 23 have received VTD. Clinical characteristics are shown in Table 1. At the time of analysis, 90 and 19 patients in the CyBorD and VTD are alive of which 25 and 9, respectively, have progressed. ORR and VGPR rates after a median of 4 cycles of induction were 94% and 56.4% for patients treated with CyBorD, and 91% and 78.2% for VTD, respectively (p=0.3 and 0.05). At day-100 post-ASCT, a ³VGPR rate of 84% and 94% was observed for the CyBorD and VTD groups, respectively (p=0.2). MRD negativity and CR rates were higher in the group receiving VTD (36.8% vs 27%, and 61% vs 38%, p=0.3 and 0.01). Furthermore, median OS and PFS did not differ among both groups (p=0.8 and 0.9, respectively) (Fig1a and Fig1b). In Conclusion: CyBorD and VTD appeared to be effective treatment options for transplant-eligible myeloma patients with similar response rates. Our study is in agreement with that reported by the IFM group, showing a higher rate of³VGPR after induction and day-100 post-ASCT in the VTD group. MRD negativity and CR rate appears also higher in the VTD group suggesting a higher degree of response by using animmunomodulatory drug and a proteasome inhibitor together. [Display omitted] [Display omitted] DisclosuresJimenez-Zepeda:Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene, Janssen, Amgen, Onyx: Honoraria. Bahlis:Janssen: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria; Onyx: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; BMS: Honoraria. Neri:Celgene and Jannsen: Consultancy, Honoraria.

Significant Differences in Stem Cell Transplant Utilization Rates (STUR) of Autologous Hematopoietic Cell Transplant (AHCT) in Multiple Myeloma (MM) Based on Ethnicity without Differences in Efficacy. a CIBMTR Report

Background: Recent studies confirm the importance of upfront AHCT for MM even in the era of new agents. Previous studies have shown differences in utilization without a difference in efficacy of AHCT in Black versus White patients. No such data is available for Hispanic (H) patients, the fastest growing segment of the US population. We studied utilization and outcomes of AHCT in MM patients based on ethnicity.Methods: We assessed AHCT performed for MM in adults from 2008-2014 registered in the CIBMTR (N=28,450) a voluntary transplant database which captures approximately 80% of MM AHCT activity in the US. The SEER 18 database was used to estimate the incidence of MM and calculate stem cell transplant utilization rate (STUR). From this cohort, among those who received a peripheral blood with melphalan conditioning and had at least 100 days follow up data (N=24,102), we analyzed transplant-related mortality (TRM), progression-free survival (PFS) and overall survival (OS). Given the large sample size, a p value of <0.01 was considered statistically significant a priori.Results: There were 18,046 non-Hispanic Whites (NHW), 4123 non-Hispanic Blacks (B) and 1933 H patients. The H group was younger (median age at AHCT of 57 vs. 61 years for NHW vs. 58 for B; p <0.001). Fewer patients over the age of 60 were transplanted in the H (39%) and B group (42%) vs. the NHW group (56%). More females underwent AHCT among H (43%) and B (50%) compared to NHW (41%) (p<0.001). A lower Karnofsky score (<90%) was more common in B (44%) vs. H (39%) and NHW (39). HCT-CI >3 was more common in B (38%) and NHW (34%) vs. H (24%) (p<0.001). There were more Stage III patients at diagnosis in the H (57%) vs. B (54%) and NHW (52%) (p<0.001). More H (48%) compared to 44% NHW and 45% B were in ≥VGPR pre-transplant (p=0.005).Within the H patients, 1590 identified as H White (HW), 64 as H Black (HB) and 279 as H Other (HO). There were no differences noted for age, gender, HCT score, and pre-transplant stage between these subgroups. There was a higher number of patients with stage 3 disease noted in the HW (59%) vs. HB (55%) and HO (47%) p = 0.008.The STUR progressively increased from 2008 to 2013 for all 3 groups but was highest for NHW (37.8%) followed by B (20.5%) and H (16.9) (Table 1). Post-transplant outcomes are shown in Table 2. On multivariate analysis, ethnicity had no effect on OS but increasing age, male gender, KPS <90, HCT-CI>3, >12 months from diagnosis to AHCT, melphalan conditioning 140 mg/m2 and <CR pre-AHCT adversely affected OS. (Figure).Conclusions: Transplant utilization among newly diagnosed MM patients remains low overall at 25% in 2013. Although it is increasing among all ethnicities, STUR remains significantly lower among H, followed by B compared with NHW. H patients who undergo AHCT tend to be younger and fitter with worse disease. Ethnicity did not impact AHCT outcomes. Additional analyses are necessary to determine why there is a disproportion of B and H patients who fail to undergo AHCT. Further efforts are needed to increase transplant utilization for all eligible MM patients, with an emphasis on groups underutilizing transplant. [Display omitted] [Display omitted] DisclosuresKrishnan:celgene: Consultancy, Speakers Bureau; takeda: Consultancy, Speakers Bureau; janssen: Consultancy, Speakers Bureau; onyx: Speakers Bureau.

First in Human Study with GSK2857916, an Antibody Drug Conjugated to Microtubule-Disrupting Agent Directed Against B-Cell Maturation Antigen (BCMA) in Patients with Relapsed/Refractory Multiple Myeloma (MM): Results from Study BMA117159 Part 1 Dose Escalation

BackgroundExpression of BCMA, a cell surface receptor in the TNF superfamily, is restricted to B cells at later stages of differentiation and is requisite for the survival of long lived plasma cells. BCMA is expressed on MM cells at variable levels.GSK2857916 is a humanized IgG1 anti-BCMA antibody conjugated to the microtubule disrupting agent monomethyl auristatin-F via a stable, protease-resistant maleimidocaproyl linker. Upon binding to BCMA, GSK2857916 is rapidly internalized and active drug is released within the cell. GSK2857916 also exhibits enhanced antibody-dependent cell-mediated cytotoxicity resulting from afucosylation of the FC domain which increases affinity to FCγRIIIa expressed on immune effector cells. The rationale for investigating GSK2857916 in MM is supported by the restricted pattern of BCMA expression and by evidence from preclinical studies.MethodsBMA117159 (NCT02064387) is a Phase I open-label study investigating safety, pharmacokinetics (PK), pharmacodynamics (PD), antidrug antibodies (ADA) and clinical activity of GSK2857916 in relapsed/refractory MM and other hematologic malignancies expressing BCMA. Dose escalation (Part 1) is conducted exclusively in MM patients; primary objective is safety, determination of maximum tolerated dose (MTD) and recommended phase 2 dose. GSK2857916 is administered every 3 weeks as a1 hr intravenous infusion with no mandatory prophylaxis for infusion related reactions (IRR). Bayesian Logistic Regression Model is applied for dose recommendations. Eligible MM patients must have prior treatments with alkylators, proteasome inhibitors, immunomodulators and stem cell transplantation, if transplant eligible, and have documented disease progression on or within 60 days of last therapy. Additional key inclusion criteria include: ANC >1x109/L; hemoglobin >8 g/dL; PLT >50x109/L; INR <1.5; PTT <1.5xULN; total bilirubin ≤1.25xULN; AST and ALT <1.5xULN; serum creatinine <1.2xULN or calculated creatinine clearance >60 mL/min; albuminuria <500mg/24hr; LVEF >50% and troponin <1xULN. Patients remain on treatment until progression, unacceptable toxicity, consent withdrawal or completing 16 treatment cycles. Blood is collected for PK and ADA analyses; blood and bone marrow aspirates are collected for PD analyses.ResultsTo date 24 MM patients have enrolled and completed the 21 day DLT observation period. Patients were enrolled at the following 8 dose levels: 0.03 (n=1); 0.06 (n=1); 0.12 (n=4); 0.24 (n=4); 0.48 (n=4); 0.96 (n=3); 1.92 (n=4), and 3.4 mg/kg (n=3). The median age is 60 years (range 39-71); 50% are male. Eighty-three percent received ≥4 prior lines. Sixty-three percent had IgG and 29% had IgA types. Seven patients (29%) had adverse cytogenetics defined as del17p13, or t(4;14) . Overall, 23 patients (96%) experienced adverse events (AE); the most frequent (≥20%) regardless of cause were nausea (42%), fatigue (38%), anemia (29%), chills (29%), pyrexia (29%), thrombocytopenia (29%), dry eye (21%), and hypercalcemia (21%). Grade 3/4 AEs reported in ≥10% of patients were thrombocytopenia, anemia, and neutropenia. Eight serious AEs were reported in 6 patients with 1 event of limbal stem cell dysfunction considered drug related; this event has not resolved. There were no AEs leading to treatment discontinuation. Four patients required dose reduction due to AEs: ocular toxicity (n=1), corneal disorder/ocular toxicity (n=1), dry eyes (n=1), and keratitis (n=1). IRRs (all Grade 1 or 2) were reported in 7 patients (29%) across dose levels and occurred with the first dose administration. The most frequent symptoms were chills. No DLTs were reported. Sixteen patients discontinued treatment due to disease progression (n=14), patient decision (n=1), completing 16 cycles of scheduled treatment (n=1); 8 patients are ongoing. There was1 MR at 0.24 mg/kg, and 1 VGPR, 3 PR, and1 MR at doses ≥0.96 mg/kg; resulting in a clinical benefit rate of 25% (unconfirmed responses).ConclusionGSK2857916 was well tolerated with no DLTs up to 3.4mg/kg q3w; MTD was not reached. AEs were manageable with ocular toxicity emerging as the most frequent reason for dose modifications. Clinical activity has been seen at higher doses. Complete safety, ADA, PD, and clinical activity data from all dose levels evaluated in Part 1 for q3w schedule will be presented.Study is funded by GlaxoSmithKline; drug linker technology is licensed from Seattle Genetics DisclosuresCohen:Janssen: Consultancy; Bristol-Meyers Squibb: Consultancy, Research Funding. Trudel:Glaxo Smith Kline: Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Equity Ownership, Honoraria; Oncoethix: Research Funding; BMS: Honoraria; Amgen: Honoraria. Richardson:Celgene: Membership on an entity's Board of Directors or advisory committees. Anderson:Takeda: Speakers Bureau; AMGEN/Onyx: Speakers Bureau; Celegene: Speakers Bureau. DeWall:GlaxoSmithKline: Employment, Equity Ownership. Ellis:GlaxoSmithKline: Employment, Equity Ownership. He:GlaxoSmithKline: Employment, Equity Ownership. Mazumdar:GlaxoSmithKline: Employment, Equity Ownership. Wang:GlaxoSmithKline: Employment, Equity Ownership. Opalinska:GlaxoSmithKline: Employment, Equity Ownership. Voorhees:GlaxoSmithKline: Research Funding; Celgene, BMS: Honoraria; Takeda: Consultancy, Honoraria; Novartis: Consultancy.

Impact of Novel Agents on Frequency of Second Salvage Autologous Transplantation in Patients with Multiple Myeloma

Introduction:High dose melphalan followed by autologous hematopoietic stem cell transplant (ASCT) is the standard of care in eligible multiple myeloma (MM) patients (pts). It is common practice to collect sufficient stem cells for two transplants, for the first ASCT immediately after induction, and for salvage ASCT following disease progression. We investigated the frequency of salvage second ASCT in the era of novel agents to determine if there has been a change in practice.Methods:We retrospectively reviewed medical records of MM pts who had stem cells collected for two ASCTs from 03/1996 to 12/2014. We then compared pts who received their first ASCT prior to January 2007 to those after this time. We excluded pts who received their second transplant as part of a clinical protocol, who received subsequent allogenic transplants, and pts who received 2 ASCT transplants as part of initial therapy. Fisher's exact test was used to assess significance of categorical independent variables and t-test was used to assess significance of continuous variables.Results:Forty of 506 pts (7.9%) received salvage second ASCT (Fig 1). Among 195 MM pts who received their first ASCT before 2007, 19 pts (9.7%) received salvage ASCT. After 2007, 21 of 311 MM pts (6.7%) received salvage ASCT (P= 0.24). When comparing salvage ASCT in the two time periods, no significant differences were noted, with theexception of a slightly lower KPS status (80% vs 70%, P=0.001), and the use of novel agents before the salvage therapy (0/19 (0%) vs 17/21 (81%), p <0.001). Otherwise the clinical characteristics, prior response and response duration, and initial stage were similar. Prior to 2007, 6 of 44 (14%) pts older than 65 years received salvage ASCT, whereas after 2007 only 3 of 110 (3%) patients received salvage ASCT (p = 0.017).Conclusions:Outside of clinical trials, the use of salvage second ASCT for relapsed MM is not frequent, and was noted to be decreasing further after 2007. We speculate that this 30% relative reduction in the frequency of salvage ASCT after 2007 is likely explained by the introduction of novel agents such as bortezomib and lenalidomde into the clinical practice, the use of maintenance therapy post-ASCT, and more non-ASCT options for salvage treatment after relapse. Further studies are needed to investigate the optimal timing for salvage ASCT and the patients who will best benefit from such treatment. [Display omitted] DisclosuresWingard:Astellas: Consultancy; Gilead: Consultancy; Ansun: Consultancy; Fate Therapeutics: Consultancy; Merck: Consultancy.

Consolidation Followed By Maintenance Therapy Versus Maintenance Alone in Newly Diagnosed, Transplant Eligible Patients with Multiple Myeloma (MM): A Randomized Phase 3 Study of the European Myeloma Network (EMN02/HO95 MM Trial)

▪BackgroundThe role of up-front consolidation for newly diagnosed, transplant eligible MM (NDMM) patients (pts) has not yet been prospectively addressed in the novel agents era.MethodsThe EMN02/HO95 trial was designed to randomly (R) compare (R1) 4 cycles of bortezomib-melphalan-prednisone (VMP) vs high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT), either single or double, as intensification therapy after induction with bortezomib-cyclophosphamide-dexamethasone (VCD) (M Cavo et al, ASCO 2016, abstract #8000). A second randomization to consolidation therapy with 2 cycles of VRD vs no consolidation (R2) was performed after intensification, to be followed by lenalidomide maintenance (lenalidomide 10 mg continuously) until progression or toxicity in both arms. (VRD: bortezomib 1.3 mg/m2 intravenously days 1, 4, 8, 11; lenalidomide 25 mg orally days 1 - 21; dexamethasone 20 mg orally days 1, 2, 4, 5, 8, 9, 11, 12 of a 28 days cycle). Primary study end points were progression-free survival (PFS) from R1 and PFS from R2. A first planned interim analysis for R2 was performed in July 2016 when at least 33% (= 172) of the required events for PFS had been observed.ResultsFrom February 2011 to April 2014, 1510 pts aged ≤ 65 years with symptomatic MM were enrolled, of whom 1499 were eligible. Of these, 1211 were randomized (stratification by ISS stage) to VMP (505 pts) or HDM (1 or 2 ASCT) (706 pts). For R2 903 eligible patients were randomized to consolidation (459 pts) or no consolidation (444 pts). Median follow up from R2 was 25 months (maximum 53). Response status at time of R2 was ≥ CR (23%), ≥ VGPR (67%), ≥ PR (93%), and will be updated for status at start of maintenance. At the time of analysis, 258 events for PFS after R2 had been reported. 3-year. PFS from R2 was 62% in all patients, i.e., 60% without consolidation and 65% in patients with consolidation, and median PFS had not yet been reached. PFS from R2 with adjustment for R1 was prolonged in pts randomized to VRD (HR=0.78; 95% CI=0.61-1.00; P=0.045), a benefit retained across predefined subgroups with revised ISS stage III (HR=0.67; P=0.26) and in patients randomized in R1 to VMP (HR=0.76; P=0.19) and to HDM (HR=0.79; P=0.13). The benefit of consolidation was observed in patients with low-risk cytogenetics (HR=0.68; P=0.03), but not in patients with high-risk cytogenetics (del(17p) and/or t(4;14) and/or t(14;16); HR=1.03; P=0.91). At 3 years OS from R2 was 86% and 87%, respectively. Toxicity from VRD was limited with 5% CTCAE grade 4, mainly hematological.ConclusionsConsolidation treatment with VRD followed by Lenalidomide maintenance until progression or toxicity shows promising results as compared to maintenance alone for younger NDMM pts, but further study follow-up is needed.This trial was registered at www.trialregister.nl as NTR 2528, EudraCT 2009-017903-28 This trial was supported by unrestricted grants from Celgene and Janssen. DisclosuresSonneveld:Celgene: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria. Dimopoulos:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria; Genesis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Carella:Millenium: Speakers Bureau; Genentech: Speakers Bureau. Ludwig:Janssen: Speakers Bureau; BMS: Speakers Bureau; Amgen: Research Funding, Speakers Bureau; Takeda: Research Funding, Speakers Bureau. Driessen:janssen: Consultancy; celgene: Consultancy; Mundipharma-EDO: Honoraria, Membership on an entity's Board of Directors or advisory committees. Gay:Celgene: Honoraria; Mundipharma: Other: Advisory Board; Amgen: Honoraria; BMS: Honoraria; Janssen-Cilag: Other: Advisory Board; Takeda: Honoraria, Other: Advisory Board. Mellqvist:Mundipharma: Honoraria; Celgene: Honoraria; Novartis: Honoraria; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Zweegman:Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria, Research Funding. Schjesvold:Janssen: Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Palumbo:Takeda: Employment, Honoraria; Janssen Cilag: Honoraria. Cavo:Celgene: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria.

VD Versus VTD Induction: Similar Efficacy in Controlling Disease in Transplant Eligible Multiple Myeloma Patients Outside Clinical Trials

Autologous stem cell transplant (ASCT) remains the standard of care for Multiple Myeloma (MM) patients younger than 70 years old. The role of induction therapy is crucial within a program of high-dose therapy since deeper is the response before, higher is the outcome of transplant.In this study, we analyzed a real life setting of patients treated with three different induction approaches: VAD (Vincristine-Adriamycin-Dexamethasone), VD (Bortezomib - Dexamethasone), and VTD (Bortezomib-Thalidomide-Dexamethasone) in terms of depth of response, 2 years therapy-free rate and toxicity.One hundred and sixty-three MM patients (pts) were included in the analysis: 62 pts treated with VAD (38%), 44 with VD (27%) and 57 with VTD (35%). In VTD group 49 pts (86%) received Bortezomib subcutaneously. As shown in Table 1, patients of the three groups were similar for D&S stage (p 0.59), a higher rate of ISS stage 3 was observed in VAD group (p=0.019), patients in VTD group were significantly older (p=0.024), median follow-up was significantly lower in VTD pts (p<0.001). The overall response rates after induction were similar in all three groups (p=0.156), with higher rate of responses of good quality (CR+VGPR) for patients treated with Bortezomib-based combinations: VAD 24.2%, VD 52.3%, VTD 63.2% (p<0.001). No difference was observed between VTD and VD (p=0.258). A different pattern of responses was observed after transplant, VTD, in fact, was superior to VAD (p<0.001) and VD (p=0.012), while no difference was highlighted between VAD and VD (p=0.352). As a matter of fact, 2 years therapy-free rate were: 48% for patients treated with VAD vs 73% with VD vs 74% with VTD (p=0.189). Of note, however, bortezomib base therapy maintained its superiority with respect to VAD (p=0.03). No differences were observed between VD and VTD regimens in terms of toxicity of any grade and type (52.3% VD vs 52.6% VTD, p> 0.9), and of discontinuation rate (14% in VTD and 18% in VD, p=0.395). The incidence of all grades peripheral neuropathy (PN) was similar between VD and VTD (28.2% and 31.4% p=0.835), but grade 3-4 PN was significantly higher in VD group (no patients in VTD vs 18% in VD pts, p=0.078), probably due to different way of Bortezomib administration in VTD group (86% of pts received subcutaneous Bortezomib).In this study, we confirm that Bortezomib-based regimens are better than VAD in terms of overall response rate, good quality responses and long-term disease control. VTD is superior to VD in terms of good quality responses after transplant but disease control at 2 years is similar. [Display omitted] DisclosuresCorso:Janssen-Cilag: Honoraria.

Soluble PD-L1: A biomarker to predict progression of autologous transplantation in patients with multiple myeloma.

Autologous hematopoietic stem cell transplantation (AuHSCT) is standard in treating eligible multiple myeloma (MM) patients. However, the outcome after treatment is highly variable. We used ELISA to analyze the levels of soluble PD-L1 (suPD-L1) in bone marrow (BM) plasma from 61 patients with MM at 100 days after AuHSCT. Patients were classified into high (H) and normal-to-low (NL) groups depending on their suPD-L1 levels. Among patients who had a very good partial response (VGPR) or better after AuHSCT, those in the H-group had a shorter response period (RpSCT) as well as shorter overall survival (OS) than those in the NL-group. Multivariate analyses confirmed that a high suPD-L1 level and high-risk cytogenetic abnormalities are independent factors for RpSCT. Our data suggest that suPD-L1 in the BM plasma of MM patients who have VGPR or better after AuHSCT could be used as a biomarker to predict outcome.

Abstract CT034: A phase I study of GSK2857916, a BCMA-directed monoclonal antibody conjugated to microtubule-disrupting agent in patients with relapsed, refractory multiple myeloma and other BCMA-expressing hematologic malignancies

Abstract Background: Expression of B cell maturation antigen (BCMA), a cell surface receptor belonging to the tumor necrosis factor receptor superfamily, is restricted to B cells at later stages of differentiation and is requisite for the survival of long lived plasma cells [Darce, 2007; O’Connor, 2004]. BCMA is also expressed on multiple myeloma (MM) cells and at various frequencies on cells from other B cell malignancies. GSK2857916 is a humanized, afucosylated IgG1 anti-BCMA antibody conjugated to the microtubule disrupting agent monomethyl auristatin-F (MMAF) via a stable, protease resistant maleimidocaproyl linker. Upon binding to BCMA, GSK2857916 is rapidly internalized and active drug is released within the cell. In addition, GSK2857916 exhibits enhanced antibody-dependent cell-mediated cytotoxicity resulting from afucosylation which increases the affinity of the antibody's Fc domain to FCγRIIIa expressed on immune effector cells. The rationale for the investigation of GSK2857916 in MM and other BCMA-positive hematologic malignancies is supported by the restricted pattern of BCMA expression, and by evidence from preclinical studies [Tai, 2015]. Methods: BMA117159 is a Phase I, open-label, study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary antitumor activity in adult patients with relapsed/refractory MM or select, BCMA-expressing hematologic malignancies. Seventeen MM patients have been enrolled as of 26 January 2016 into the ongoing dose escalation phase with the once every 3 weeks intravenous dosing schedule. A continual reassessment method applied to dose limiting toxicity findings guide dose escalation decisions and maximum tolerated dose determination. Expansion cohorts will include patients with MM and other BCMA-expressing hematologic malignancies. Eligible MM patients are required to have undergone stem cell transplant or be considered transplant ineligible, to have received prior treatment with alkylators, proteosome inhibitors and immunomodulators, and to have documented disease progression on or within 60 days of completion of last therapy. Documented BCMA expression is required for patients with other hematologic malignancies. ClinicalTrials.gov identifier: NCT02064387 Study is funded by GlaxoSmithKline Citation Format: Larry D. Anderson, James Cavet, Adam D. Cohen, Yan Y. Degenhardt, Catherine E. Ellis, Fiona Germaschewski, Nikoletta Lendvai, Edward Libby, Joanna Opalinska, Rakesh Popat, Isabelle Pouliquen, Paul G. Richardson, Keith E. Stockerl-Goldstein, Heather J. Sutherland, Suzanne Trudel, Peter M. Voorhees, Jeffrey Wetherington. A phase I study of GSK2857916, a BCMA-directed monoclonal antibody conjugated to microtubule-disrupting agent in patients with relapsed, refractory multiple myeloma and other BCMA-expressing hematologic malignancies. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT034.

MRD-driven treatment paradigm for newly diagnosed transplant eligible multiple myeloma patients.

MRD-driven treatment paradigm for newly diagnosed transplant eligible multiple myeloma patients

Immunoparesis Recovery As Predictor Marker of Progression after Autologous Stem Cell Transplantation in Multiple Myeloma

BACKGROUNDHigh dose therapy followed by autologous stem cell transplantation (ASCT) remains the standard of care, especially in Europe, for young and eligible multiple myeloma patients (usually younger than 65 years old).Immunoparesis is defined as a reduction (below the lower normal limit) in the levels of 1 or 2 uninvolved immunoglobulins (Ig) and it is related to a reversible suppression of B lymphocytes that correlates inversely with disease stage. B Lymphocyte reconstitution begins at 3 months after ASCT, with maximum B lymphocyte levels at 1 year after ASCT.AIMSThe goal of the present study was to investigate the role of the immunoparesis recovery after ASCT as predictor of relapse or progression in multiple myeloma (MM).METHODSWe reviewed medical records of MM patients who underwent to ASCT at University Hospital of Salamanca between 1992 and 2013. The primary endpoint was time to relapse or progression from ASCT. Ig (Ig G, Ig A e Ig M) were collected at the time of diagnosis, before ASCT, every 3 months during the first year after ASCT, and every year up to 5 years after ASCT among eligible patients until the relapse or disease progression.RESULTS106 multiple myeloma patients who underwent ASCT were included in the analysis. Conventional chemotherapy was administered as induction regimen in 69 patients (65%), whereas novel agents were used in 37 patients (35%).Most patients had immunoparesis at diagnosis (91%) and at the moment of ASCT as well (94%). After a median follow-up of 62 months, median time to progression or relapse (TTP) from ASCT was 31 months (95 % CI: 24.1 - 37.1 months). MM patients with immunoparesis 1 year after ASCT had a significantly shorter median TTP as compared with patients without immunoparesis (33.5 months vs 94.2 months; HR: 2.14, 95% CI: 1.13-4.05; p=0.019). In the group of patients with reduction of both Igs, median TTP was slightly inferior than in the group with reduction of only one of them(33.5 vs 36.4 months, p=0.03).Presence of ISS 3, high-risk cytogenetics at diagnosis, less than partial response achieved before and three months after ASCT were also identified as predictors of progression. Multivariate analysis selected immunoparesis 1 year after ASCT as an independent variable for relapse or progression (HR: 5.97, 95% CI: 1.63-21.88; P=0.007).CONCLUSIONSThe lack of immunoparesis recovery at 1 year after ASCT in MM patients is associated with significantly higher risk of relapse or progression and this group of patients could potentially benefit of continuous treatment after ASCT to enhance the immune recovery. DisclosuresOcio:Array BioPharma: Consultancy, Research Funding; Celgene: Consultancy, Honoraria; Amgen/Onyx: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy; Mundipharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; MSD: Research Funding; Pharmamar: Consultancy, Research Funding; Janssen: Honoraria. Puig:The Binding Site: Consultancy; Janssen: Consultancy. Mateos:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy; BMS: Consultancy; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees.