ALBERT

Description: Introduction: Novel treatments have significantly improved outcomes for multiple myeloma (MM) patients, and HRQoL is an increasingly important endpoint to measure outcomes. This study explores patients' HRQoL in Relapsed/Refractory MM (RRMM) patients receiving second or third line lenalidomide or bortezomib treatment and assesses HRQoL changes from baseline for patients completing the study and those discontinuing. Methods: A multicenter, observational 6-month study was conducted in Italy, Germany, France, UK, Ireland, and Belgium in RRMM patients starting second- or third-line treatment with bortezomib or lenalidomide. HRQoL/functioning and symptoms of patients were measured via 3 EORTC patient questionnaires and changes from baseline were assessed at month 6 and study discontinuation. Clinical significance in HRQoL score changes was assessed against distribution-based minimal important differences (MID; Table). HRQoL domains considered included 15 domains from EORTC Quality of Life Core Questionnaire (QLQ-C30), 4 from EORTC QLQ-Multiple Myeloma (QLQ-MY20), and 3 from EORTC QLQ-Chemotherapy-Induced Neuropathy (CIPN20). Domain scores ranged from 0 to 100. For functional domains, higher HRQoL/functioning scores indicated better HRQoL/functioning; for symptom domains, higher symptom scores indicated greater symptom burden. Results: A total of 258 patients (mean age, 70 yrs; 54% male) were included in the study by 33 sites from Dec 2010 to July 2014. At baseline, the median time since diagnosis was 2.8 years for lenalidomide and 3.9 years for bortezomib; an ECOG performance status 〉2 was reported in 6.2% of lenalidomide patients (n=10) vs 3.1% of bortezomib (n=3); 8.9% (n=23) reported starting third line treatment (lenalidomide: 6.2% (n=10); bortezomib: 13.5% (n=13)). Whereas 5.6% (n = 9) of patients had received dialysis prior to entering the lenalidomide cohort, none had received dialysis in the bortezomib cohort. Chronic heart failure at baseline was more often observed for lenalidomide (14.8%, n=24) vs bortezomib (8.3%, n=8). EORTC questionnaires were completed by 251 (97.3%), 137 (53.1%), and 56 (21.7%) of patients at baseline, month 6, and study discontinuation, respectively. Out of 162 pts receiving LEN, 64 (39.5%) discontinued the study before 6 months, 6.2% (n=10) due to disease progression, 16.0% (n=26) due to treatment discontinuation, and 17.3% (n=28) due to other reasons (including death, lost to follow-up, withdrawn consent). Out of 96 patients receiving bortezomib, 53 (55.2%) discontinued the study: 10.4% (n=10) due to disease progression, 27.1% (n=26) due to treatment discontinuation, and 17.7% (n=17) due to other reasons (including death, lost to follow-up, withdrawn consent). At study completion (month 6), HRQoL reductions from baseline were observed for only 1 of 22 domains in each cohort: mean change (SEM) of 10.9 (2.8) for Diarrhoea domain in the lenalidomide cohort and -8.5 (3.5) for Global Health Status/QoL domain in the bortezomib cohort, indicating relative stability of HRQoL in patients on continued treatment within the 2 cohorts. For patients who discontinued the study prior to 6 months due to disease progression or treatment discontinuation, clinically meaningful declines in HRQoL exceeding the MID were more often observed in the bortezomib cohort (8 of 22 domains), than in the lenalidomide cohort (1 of 22 domains) (Table 1). Conclusions: This observational study showed that HRQoL could be maintained under continued treatment in both the lenalidomide and bortezomib cohorts. However, higher progression and treatment discontinuation rates were observed in the bortezomib cohort and study discontinuation was often associated with clinically meaningful deteriorations in HRQoL for bortezomib-treated patients, but not for lenalidomide-treated patients. The findings of this study are of potential relevance to future MM studies, both in the relapsed/ refractory and newly diagnosed setting. HRQoL of patients with early discontinuation has not always been reported separately from patients who discontinued fixed duration treatment in MM studies. Future studies should address the question of HRQoL separately at early discontinuation, for all current and future treatment alternatives approved in MM. Disclosures Kyriakou: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Murphy:Celgene: Honoraria. Petrucci:Celgene: Honoraria; Janssen-Cilag: Honoraria; Amgen: Honoraria; Mundipharma: Honoraria; BMS: Honoraria. Bacon:Celgene Corporation: Employment, Equity Ownership. Lewis:Celgene Corporation: Employment, Equity Ownership. Gilet:Celgene: Consultancy. Arnould:Celgene: Consultancy. Vande Broek:Celgene: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Leleu:Janssen: Honoraria; Novartis: Honoraria; Celgene: Honoraria; BMS: Honoraria; Amgen: Honoraria.

Description: Background: RI occurs in ≈ 20%-30% of newly diagnosed MM pts and is associated with poor prognosis (Knudsen et al. Eur J Haematol. 2000; Kyle et al. Mayo Clin Proc. 2003). Data from 2 pivotal trials (MM-002, MM-003) suggested comparable efficacy and tolerability of POM + LoDEX in pts with or without moderate RI (Siegel ASH 2012; Weisel ASCO 2013). However, these trials excluded pts with severe RI. MM-013 (NCT02045017) is a European multicenter, open-label phase 2 study designed to assess the efficacy, safety, and pharmacokinetics of POM + LoDEX in RRMM pts with moderate or severe RI, including those on dialysis. Methods: The trial is enrolling RRMM pts (N = 80) across 3 cohorts: cohort A (moderate RI, estimated glomerular filtration rate [eGFR] ≥ 30 to 〈 45 mL/min/1.73 m2, n = 33), cohort B (severe RI without dialysis, eGFR 〈 30 mL/min/1.73 m2, n = 33), and cohort C (severe RI requiring dialysis, n = 14). Pts must have MM-related RI and have received ≥ 1 prior Tx (including lenalidomide). POM 4 mg is administered on days 1-21 of a 28-day cycle and LoDEX 40 mg/day (20 mg for pts aged 〉 75 yrs) on days 1, 8, 15, and 22 until progressive disease (PD) or unacceptable toxicity. At the time of submission of this abstract, 17 pts terminated Tx; this abstract focuses on tolerability in these pts. Results: This trial is still recruiting; at the time of data cutoff for this abstract, 39 pts were enrolled. Data are included for 17 pts who discontinued Tx. Of all 39 pts, 12 were assigned to cohort A, 18 to cohort B, and 9 to cohort C. The median age of the total population was 72 yrs (range, 52-86 yrs), with 67.7% being male. The median number of prior lines of therapy was 4.0 (3.5 in cohort A, 5.0 in cohort B, and 3.0 in cohort C). This distribution was similar in the 17 pts who discontinued Tx so far (4, 7, and 6 in cohorts A, B, and C, respectively), with a median age of 72 yrs and 58.8% being male. Reasons for discontinuation of Tx were PD (7 pts), adverse events (AEs; 3 pts), death (5 pts: 2 pts due to PD, 2 pts due to infections, 1 pt due to hyperkalemia), and other reasons (2 pts: 1 pt aged 86 yrs with general health problems, 1 pt with increasing RI). Median Tx duration in these pts was 6.9 weeks in cohort A, 12.6 weeks in cohort B, and 12.9 weeks in cohort C. The dosage of POM was reduced to 3 mg in 3 pts (1 patient in each cohort), in all cases due to an AE (thrombocytopenia in 2 pts, pneumonia in 1 pt). However, no further Tx reductions occurred. The most frequent toxicity of any grade in the pts who discontinued was hematologic (82.4% [14 pts]), notably neutropenia in 58.8% (50% in cohort A, 42.9% in cohort B, 83.3% in cohort C), anemia in 52.9% (50% in cohort A, 28.6% in cohort B, 83.3% in cohort C), and thrombocytopenia in 52.9% (75% in cohort A, 14.3% in cohort B, 83.3% in cohort C). Grade 3/4 neutropenia occurred in 47.1%; grade 3/4 thrombocytopenia occurred in 35.3%. Notably, febrile neutropenia was reported in only 1 pt in cohort A. Granulocyte colony-stimulating factor was used in 52.9% of pts. Non-hematologic AEs were less frequent. Infections occurred in 7 pts (41.2%), all of which were pulmonary infections, with the exception of 1 case of nasopharyngitis. Asthenia (23.5%) and fatigue (23.5%) occurred predominantly in cohort C. No thromboembolic events or secondary primary malignancies have been reported to date. Conclusions: These data suggest that the combination of POM and LoDEX can be safely administered in pts with RI. A starting dose of POM 4 mg can be used throughout all stages of RI, and the side effects seen in this population have been previously reported with POM use (ie, mainly hematologic events and infections). Rates of neutropenia and thrombocytopenia are similar to reports in a non-RI population. Dose modifications should be considered in pts who develop neutropenia and thrombocytopenia; in pts showing signs of infections, dose interruptions may be considered. Disclosures Off Label Use: Pomalidomide in MM patients with renal insufficiency.. Dimopoulos:Janssen: Honoraria; Celgene: Honoraria; Janssen-Cilag: Honoraria; Genesis: Honoraria; Onyx: Honoraria; Novartis: Honoraria; Amgen: Honoraria. van de Donk:Janssen Pharmaceuticals: Research Funding; Amgen: Research Funding; Celgene: Research Funding. Gamberi:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Kueenburg:Celgene Corporation: Consultancy, Honoraria. Rosettani:Celgene Corporation: Employment. Collins:Celgene Corporation: Employment. Lersch:Celgene Corporation: Employment. Bacon:Celgene Corporation: Employment, Equity Ownership. Weisel:Noxxon: Consultancy; Celgene: Consultancy, Honoraria, Other: Travel Support, Research Funding; BMS: Consultancy, Honoraria, Other: Travel Support; Novartis: Other: Travel Support; Janssen Pharmaceuticals: Consultancy, Honoraria, Other: Travel Support, Research Funding; Onyx: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel Support. Sonneveld:Amgen: Honoraria, Research Funding; Karyopharm: Research Funding; SkylineDx: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding.

Description: Introduction The use of novel therapeutic agents has significantly improved both progression-free and overall survival in multiple myeloma (MM) patients. In this context, evaluating health-related quality of life (HRQoL) gains in importance. The objective of this analysis is to explore patients’ HRQoL associated with 2nd and 3rdline treatments for Relapsed/Refractory MM (RRMM) and to compare HRQoL in those patients that completed 6 months of treatment vs. patients who discontinued from the study earlier. Methods A multicenter observational study is being conducted in 34 sites in Italy, Germany, France, UK, Ireland and Belgium in RRMM patients starting 2nd or 3rd line bortezomib- or lenalidomide-based treatment. HRQoL and symptoms of patients are assessed at baseline, month 3, and month 6 or discontinuation visit using two EORTC questionnaires: 1) Quality-of-Life Core Questionnaire (QLQ-C30) including 15 domains (Global Health Status/QoL, Physical, Role, Emotional, Cognitive and  Social Functioning; Fatigue, Nausea and Vomiting, Pain, Dyspnea, Insomnia, Appetite Loss, Constipation, Diarrhea and Financial Difficulties); 2) and QLQ-Multiple Myeloma (QLQ-MY20) including four domains (Disease Symptoms, Side Effects of Treatment, Body Image and Future Perspective). All EORTC scores range 0-100. Higher HRQoL scores indicate better HRQoL, higher symptom scores indicate worse symptoms. Descriptive statistics and paired t-tests were used in this interim analysis to evaluate changes in scores from baseline. Results As of June 2013, 206 patients (mean age: 69; 51% male) were enrolled in the study and included in this interim analysis. The average time since diagnosis was 3.4 years, with 90% of patients starting 2nd line and 10% starting 3rdline treatment. Overall, EORTC questionnaires were completed by 197, 130, 84 and 34 patients at baseline, month 3, month 6 and discontinuation, respectively. A total of 84 patients received bortezomib and 117 received lenalidomide. Out of 84 bortezomib patients, 54 had already completed their final visit, split about evenly between month 6 (29 patients) and early discontinuation (25 patients, 46%). Out of 117 lenalidomide patients, 64 had completed their final visit assessment, 55 with continued treatment until month 6 and nine patients discontinuing earlier (14%). A substantial and often clinically meaningful decline in HRQoL (Minimal Important Difference, MID 〉 6, based on 1 standard error measurement, SEM, as calculated from study patients’ baseline QoL), was observed within the patient group discontinuing treatment (see Table 1). The average dosage of lenalidomide treatment was 17.0 mg/day. Bortezomib patients received vial injections at an average of 1.2 mg/m2/day, close to the pre-specified starting dose of 1.3 mg/m2/day. Bortezomib patients who discontinued early had an average number of 3.2 vials per cycle (closer to bi-weekly dosing) and continuers up to month 6 an average of 2.3 vials per cycle, closer to weekly dosing. Conclusions First results of this multicenter observational study show a strong association between treatment discontinuation and HRQoL in RRMM. While HRQoL is maintained in patients who pursue treatment, early treatment discontinuation is significantly associated with worsened HRQoL. Higher discontinuation rates were observed amongst bortezomib treated patients as compared to lenalidomide treated patients.  A direct comparison by treatment group will be performed when final data is available. Disclosures: Petrucci: Celgene: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria. Leleu:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Onyx: Consultancy, Honoraria; Leopharma: Consultancy, Honoraria; Millennium : Honoraria; Amgen: Honoraria; Novartis: Honoraria. Lewis:Celgene GmbH : Employment, Equity Ownership. Bacon:Celgene International : Employment, Equity Ownership. Arnould:Celgene: Consultancy. Welslau:Celgene: Membership on an entity’s Board of Directors or advisory committees; Janssen: Membership on an entity’s Board of Directors or advisory committees.

Description: BACKGROUND: Real-world data can provide important information on the safety profile for recommended treatment options, but these data are collected infrequently. The ongoing post-authorization safety study (PASS) MM-034 (NCT03106324) is a prospective non-interventional study in patients (pts) with newly diagnosed multiple myeloma (NDMM) who are transplant ineligible. This study allows for the collection of robust safety data for currently recommended regimens for the management of these pts. Global guidelines recommend lenalidomide (LEN) regimens, such as LEN plus dexamethasone (DEX; Rd) and LEN plus bortezomib (BORT) plus DEX (Vd), and BORT regimens, including BORT plus melphalan plus prednisone (VMP). METHODS: Transplant-ineligible adult pts with NDMM initiating therapy in centers throughout Europe are being enrolled in the ongoing MM-034 trial. Pts receiving any first-line regimen are eligible, but the decision for which treatment regimen will be used must be made prior to study inclusion. The primary endpoint is the incidence of cardiovascular events. Secondary endpoints include the incidence of renal impairment, infections, and second primary malignancies. In this analysis, the safety profiles of Rd, Vd, and VMP were compared. RESULTS: As of April 12, 2019, 145 Rd, 53 Vd, and 83 VMP pts were enrolled in the study (evaluable cohort). At the time of data cutoff, treatment was ongoing in 64.8% of Rd pts, 41.5% of Vd pts, and 61.4% of VMP pts. Median age was 79 years in Rd pts and 75 years in both Vd and VMP pts. The proportion of pts with ISS stage III disease was higher in the Vd group (24.8% Rd vs 32.1% Vd vs 24.1% VMP), and more pts in the VMP group were male (49.7% Rd vs 58.5% Vd vs 65.1% VMP). Adverse events (AEs) of all grades confirmed the expected side effects. Any-grade neutropenia occurred in 7.6%, 11.3%, and 13.3% of Rd, Vd, and VMP pts, respectively, and thrombocytopenia occurred in 6.2%, 5.7%, and 12.0%, respectively. However, any-grade febrile neutropenia was seen only in the VMP group, at 2.4%, but not in the other 2 groups. Any-grade polyneuropathy was reported in 1.4% of Rd pts, but in 18.9% of Vd pts and 19.3% of VMP pts. Any-grade infections of all kinds occurred in 28.3% of Rd pts, 41.5% of Vd pts, and 20.5% of VMP pts, with pneumonia in 3.4%, 11.3%, and 2.4% of Rd, Vd, and VMP pts, respectively. Any-grade thrombosis was reported in 4.8% of Rd pts and 3.8% of Vd pts and in no VMP pts. Grade 3/4 AEs occurred in 42.8% of Rd pts, 52.8% of Vd pts, and 43.4% of VMP pts. Grade 3/4 neutropenia was reported in 4.8%, 9.4%, and 8.4% of Rd, Vd, and VMP pts, respectively, and thrombocytopenia in 2.8%, 0%, and 8.4%, respectively. Grade 3/4 infections were lower in Rd pts (6.9% vs 24.5% Vd and 12.0% VMP); pneumonia, the most important of these, was reported in 0.7%, 5.7%, and 2.4% of Rd, Vd, and VMP pts, respectively. Grade 3/4 peripheral neuropathy was not seen in the Rd group; however, it was reported in 3.8% of Vd pts and 2.4% of VMP pts. Grade 3/4 venous thrombosis was reported in only 0.7% of Rd pts, with no events reported in the Vd and VMP groups. CONCLUSIONS: The results from this analysis, along with those from a previous analysis of cardiovascular events in the LEN-treated and non-LEN treated cohorts of pts from the European PASS MM-034 study (De Stefano, EHA 2019), provide real-world evidence for the safety profile of Rd as first-line therapy and support the role of Rd in the treatment of pts with NDMM who are transplant ineligible. Disclosures Cavo: celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel accommodations, Speakers Bureau; amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; bms: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; novartis: Honoraria; takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Tromp:Janssen: Other: Grant. Dhanasiri:Celgene Corporation: Employment, Equity Ownership. Kueenburg:Celgene: Consultancy. Rosettani:Celgene International: Employment. Martin:Celgene: Employment. Pozzi:Celgene: Consultancy. Bacon:Celgene: Employment, Equity Ownership. Gamberi:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Front-line treatment (of any type) was at the discretion of the investigator.

Description: Abstract 107 BACKGROUND: ASCO and EORTC guidelines recommend granulocyte colony-stimulating factor (G-CSF) primary prophylaxis for cancer patients with a ≥20% overall risk of febrile neutropenia (FN), and to support delivery of dose-dense regimens. CHOP-like regimens (with rituximab [R]) are the current standard of care for the management of aggressive non-Hodgkin lymphoma (NHL), but they are often associated with significant myelosuppression. Neutropenic events, particularly febrile neutropenia (FN), can be life-threatening and may lead to dose delays or reductions that compromise the efficacy of chemotherapy. In IMPACT NHL, we evaluated current practice in FN risk assessment and use of G-CSF prophylaxis in patients receiving (R)CHOP. METHODS: IMPACT NHL is a retrospective and prospective observational study conducted in 14 European countries and Australia. Physicians assessed the overall FN risk of NHL patients and their need for G-CSF prophylaxis. This analysis focuses on patients with diffuse large B-cell lymphoma (DLBCL) receiving either 2-weekly R-CHOP-14 or 3-weekly R-CHOP-21. FN risk was assessed according to EORTC guidelines (i.e. the total risk from the chemotherapy regimen plus individual patient risk factors). The primary outcome measure was the proportion of patients assessed as being at ≥20% risk of FN and who were planned to receive primary prophylaxis with a G-CSF (defined as G-CSF initiation within days 1-7 of cycle 1). RESULTS: Data were available for 1829 patients who initiated chemotherapy between 01/2005 and 08/2008; 1136 had DLBCL. The mean age±SD of patients receiving R-CHOP-21 (N=704) was 62.6±13.8 years, 51% were aged ≥65 years and 53% had Stage III-IV disease. For R-CHOP-14 patients (N=409), the mean age was 58.4±14.7 years, 41% were ≥65 years and 59% had Stage III-IV disease. In total, 434 R-CHOP-21 patients were assessed as being at high risk for FN and 47% of them actually received G-CSF primary prophylaxis (with either pegfilgrastim or daily G-CSF) (see Table). Furthermore, almost a fifth of patients assessed as being at

Description: Introduction With the increased use of first generation novel therapeutic agents and extended life expectancy of multiple myeloma, patients’ Health-Related Quality of Life (HRQoL) is gaining considerable importance, including the relapsed/refractory multiple myeloma (RRMM) setting. So far, few studies have been conducted to appreciate the physical, psychological/cognitive, financial, social health impact of living with RRMM on longer term exposure to anticancer drugs. The objective of this study was to evaluate the psychometric properties of the EORTC Quality-of-Life Core Questionnaire (QLQ-C30) and QLQ-Multiple Myeloma (QLQ-MY20) in RRMM patients. Methods A European, multicenter, observational study is being conducted in RRMM patients starting 2nd or 3rd line treatment. Patients are asked to complete the QLQ-C30 and QLQ-MY20 at baseline, month 3, and month 6 or discontinuation visit. Both generic and specific modules of EORTC questionnaires are widely used to assess HRQoL and symptoms in cancer patients. The QLQ-C30 includes 15 domains (Global Health Status/QOL, Physical Functioning, Role Functioning, Emotional Functioning, Cognitive Functioning, Social Functioning, Fatigue, Nausea and Vomiting, Pain, Dyspnea, Insomnia, Appetite Loss, Constipation, Diarrhea and Financial Difficulties); and the QLQ-MY20 includes four domains (Disease Symptoms, Side-Effects of Treatment, Body Image and Future Perspective). Construct validity was evaluated at baseline by confirming the structure using multitrait analysis and by assessing clinical validity against ECOG performance status. Internal consistency reliability was evaluated at baseline using Cronbach’s alpha. Results As of June 2013, 206 patients have been enrolled in the study and included in this interim analysis. Mean age was 69 years, with 51% male, and with an average time since diagnosis of 3.4 years. A total of 90% of patients started 2nd line treatment and 10% started 3rd line treatment. Both EORTC questionnaires were well completed by patients, with 95% of patients responding to the QLQ-C30 and MY20 at baseline and 74% and 66% of patients, respectively, completing all QLQ-C30 and QLQ-MY20 items at baseline. Substantial percentages of patients reported the best possible level of HRQoL and symptoms at baseline, i.e. zero points for Appetite Loss (61%), Constipation (51%), Diarrhea (80%), Financial Difficulties (73%) and Nausea and Vomiting (73%), respectively 100 score points for Body Image (61%). The structure of multi-item QLQ-C30 and QLQ-MY20 domains was confirmed, as was the relevance of aggregation of items into domains (Table 1 ). Both QLQ-C30 and QLQ-MY20 scores were correlated to ECOG performance status (Figure 1). Conclusions This interim analysis confirmed in RRMM patients the satisfactory psychometric properties of the EORTC QLQ-C30 and QLQ-MY20 in terms of validity and reliability, already published in other cancer conditions. Psychometric properties of both questionnaires will be confirmed when repeating the analyses on the final dataset of this study. Disclosures: Leleu: Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Onyx: Consultancy, Honoraria; Leopharma: Consultancy, Honoraria; Millennium: Honoraria; Amgen: Honoraria; Novartis: Honoraria. Petrucci:Celgene: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria. Welslau:Celgene: Membership on an entity’s Board of Directors or advisory committees; Janssen: Membership on an entity’s Board of Directors or advisory committees. Bottomley:Celgene: Consultancy, Research Funding. Bacon:Celgene International: Employment, Equity Ownership. Lewis:Celgene GmbH: Employment, Equity Ownership. Gilet:Celgene: Consultancy. Arnould:Celgene: Consultancy.

Description: Background: EU PASS is an observational, noninterventional study designed to investigate the safety of lenalidomide (LEN) and other agents in the treatment of RRMM in a real-world setting. Aims:To assess the incidence of adverse events (AEs) of special interest, including neutropenia, thrombocytopenia, venous thromboembolism (VTE), peripheral neuropathy (PN), and second primary malignancies (SPMs) in RRMM patients (pts) treated with LEN and other antimyeloma therapies according to current clinical practice. Methods: Pts with RRMM who were commencing LEN treatment were enrolled at the investigator's discretion into a LEN cohort (LEN + dexamethasone, the approved combination for the treatment of RRMM); pts who received ≥ 1 prior therapy and were commencing a non-LEN-based therapy were enrolled into a background cohort (all other treatments, including novel agents). Thromboprophylaxis was per local standard practice. AEs were graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (version 3). SPMs were defined using Medical Dictionary for Regulatory Activities (MedDRA) terms under the category Neoplasms SOC. Following protocol amendment in 2011, assessments for SPMs were to be conducted up to 36 mos after treatment discontinuation. Results: As of June 2016, 3632 pts across 269 institutions in 17 European countries were included in the safety population. Of those, 59.2% received LEN (n = 2151), 32.7% received bortezomib (BORT; n = 1188), 3.8% received thalidomide (THAL; n = 137), and 4.3% received other therapies (n = 156). The majority of pts had discontinued from treatment (97.9%; n = 3556); of the 2.1% (n = 76) ongoing pts, 66 are treated with LEN, 6 with BORT, 0 with THAL, and 4 with other substances. Baseline characteristics were similar across the cohorts. Median age was 70 yrs (range, 25-95 yrs) and 54.0% were male. Of 2985 pts with available ECOG data, 2865 (96.0%) had good performance status (ECOG score 0-2), and the remaining 4.0% had an ECOG score of 3/4. The median number of prior therapies was 1 (range, 1-6) but was higher in the LEN cohort (2; range, 1-6) than in the BORT (1; range, 1-6) and THAL (1; range, 1-5) cohorts; the proportion of pts with only 1 prior treatment was also lower in the LEN cohort (44.3%), whereas BORT was 70.8% and THAL 56.2%. Overall, 50.7% of pts (n = 1842) had grade 3/4 AEs. Grade 3/4 neutropenia occurred in 17.1%, 3.5%, and 4.4% of pts in the LEN, BORT, and THAL cohorts, respectively, and grade 3/4 thrombocytopenia in 9.2%, 7.3%, and 3.6%. The incidence rate of SPM was 3.63 per 100 pt-yrs, with 3.18 per 100 pt-yrs in the LEN cohort, 5.23 per 100 pt-yrs in the BORT cohort, 2.73 per 100 pt-yrs in THAL, and 6.48 per 100 pt-yrs in others. AEs of interest of all grades are listed in Table 1. The median duration on study treatment was 6.6 mos (range, 0.1-81.6 mos) for LEN, 4.1 mos (range, 0-63.6 mos) for BORT, and 4.6 mos (range, 0.2-36.9 mos) for THAL. Treatment discontinuation rate due to AEs was similar in each cohort (22.1% in the LEN, 20.0% in the BORT, and 21.2% in the THAL cohorts). In the LEN cohort, dose reductions occurred in 38.1% of pts, with a median time to first dose reduction due to AEs of 12.4 weeks. Treatment-emergent adverse events leading to dose reductions were similar across cohorts, with 23.7% in the LEN cohort, 21.4% in the BORT cohort, and 17.5% in the THAL cohort. Conclusions: Results of this noninterventional study in RRMM show that AEs were similar across cohorts except for higher rates of neutropenia and lower rates of PN with LEN compared with THAL or BORT. Higher rates of neutropenia did not translate into increased febrile neutropenia. Infections, independent from neutrophil counts, occurred in all cohorts, but few pts developed serious infections such as pneumonia. VTEs as well as myocardial infarctions were low throughout all cohorts. The occurrence of SPMs was generally low and comparable between cohorts. LEN was generally well tolerated. Disclosures Tholouli: Johnson and Johnson: Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Celgene: Honoraria; MSD: Speakers Bureau; Giles: Speakers Bureau. Hájek:Janssen: Honoraria; Takeda: Consultancy; BMS: Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Research Funding. Minnema:Celgene: Consultancy; BMS: Consultancy; Amgen: Consultancy; Jansen Cilag: Consultancy. 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; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genesis: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Frost Andersen:Celgene: Research Funding. Waage:Amgen: Speakers Bureau; Celgene: Consultancy, Honoraria; Novartis, Amgen, Celgene: Membership on an entity's Board of Directors or advisory committees. Crotty:BMS, Takeda, Novartis, Janssen, Roche: Honoraria. Kueenburg:Celgene International Sarl: Consultancy, Honoraria. Di Micco:Celgene: Employment. Bacon:Celgene: Employment, Equity Ownership.

Description: Background: Renal failure is a common complication for patients (pts) with MM. The incidence of renal failure increases during the course of the disease. Renal insufficiency is associated with poor prognosis in MM; however, the introduction of novel agents has led to improved survival. This trial evaluates safety, efficacy, and pharmacokinetics of pomalidomide (POM) plus dexamethasone (DEX) in pts with myeloma-related renal impairment and an eGFR 〈 45 mL/min/1.73m2as well as in pts on hemodialysis. Aims:The aim of this analysis is to summarize the safety profile of POM and DEX in pts with RRMM and renal impairment, including pts on hemodialysis. Methods: This interventional phase 2, open-label, multicenter study enrolled 3 cohorts of pts with RRMM and differing degrees of renal impairment. Cohort A included pts with moderate renal impairment (eGFR between 30 and 45 mL/min/1.73m2), cohort B included pts with severe renal impairment (eGFR ≤ 30 mL/min/1.73m2) not requiring hemodialysis, and cohort C included pts with severe renal impairment requiring hemodialysis. Enrollment occurred in parallel, and all pts received treatment with starting doses of POM 4 mg and DEX 40 mg (20 mg for pts aged 〉 75 years). All pts continued study treatment until disease progression or unacceptable toxicity. Adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for AEs v4.0. Supportive care, such as hematopoietic growth factors, was allowed; thromboembolic prophylaxis was required for all pts not on hemodialysis. Results: As of June 2016, 78 pts (30 in cohort A, 34 in cohort B, 14 in cohort C) across 19 institutions in 8 European countries were enrolled in the trial. At the time of this abstract, there were 28 pts still on treatment (15, 11, and 2 in cohorts A, B, and C, respectively). During the study, 27 pts (34.6%) discontinued treatment due to progressive disease (33.3% [n = 10/30], 41.2% [n = 14/34], and 21.4% [n = 3/14] in cohorts A, B, and C, respectively), 8 pts (10.3%) due to AEs (6.7% [n = 2/30], 8.8% [n = 3/34], and 21.4% [n = 3/14]), and 15 pts (19.2%) due to other reasons. The safety population consisted of 76 pts (29, 34, and 13 in cohorts A, B, and C, respectively). Median treatment duration was 3.8 months (range, 0.5-17.5 months) overall (4.1 months [range, 0.9-17.5 months], 4.1 months [range, 0.5-13.4 months], and 2.1 months [range, 0.5-9.2 months] in cohorts A, B, and C, respectively), and the median average daily POM dose was 4 mg/day for all cohorts. Dose reductions occurred in 12 pts (15.8%) overall (13.8% [n = 4/29], 17.6% [n = 6/34], and 15.4% [n = 2/13] in cohorts A, B, and C, respectively). Occurrence of ≥ 1 grade 3/4 AE was similar between cohorts (75.9%, 76.5%, and 76.9% in cohorts A, B, and C, respectively). In cohorts A, B, and C, the occurrence of serious AEs was 48.3%, 52.9%, and 76.9%, respectively. Overall, the most frequently reported AEs of any grade were neutropenia in 46 (60.5%) pts (69.0%, 52.9%, and 61.5% in cohorts A, B, and C, respectively) and thrombocytopenia in 32 (42.1%) pts, (48.3%, 35.3%, and 46.2% in cohorts A, B, and C, respectively). Neutropenia did not translate into febrile neutropenia, which occurred in only 1 pt each in cohorts A and B. Overall, infections were reported in 41 (53.9%) pts (55.2%, 58.8%, and 38.5% in cohorts A, B, and C, respectively), including 11 pts (14.5%) who had pneumonia (20.7%, 5.9%, and 23.1%). Rates of asthenia (20.7%, 11.8%, and 30.8% in cohorts A, B, and C, respectively) and fatigue (20.7%, 17.6%, and 30.8%) were slightly higher in pts on hemodialysis compared with pts with moderate renal impairment or severe renal impairment without hemodialysis, representative of the poor performance status and anemia (at baseline, 41.4%, 41.2%, and 61.5% in cohorts A, B, and C, respectively) noted in these pts. Conclusions: Results of this study investigating POM in combination with DEX in pts with RRMM and renal impairment show a similar AE profile as previously reported in pts without renal insufficiency. Compared with pts not on hemodialysis, slightly more non-hematologic AEs were reported in pts on hemodialysis, who have a poor performance status in comparison with other cohorts. Updated data will be presented at the meeting. Disclosures Weisel: Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Onyx: Consultancy; Amgen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Novartis: Honoraria. Dimopoulos:Genesis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: 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; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. van de Donk:Celgene: Research Funding; BMS: Research Funding; Janssen: Research Funding; Amgen: Research Funding. Ramasamy:Celgene: Honoraria, Research Funding. Streetly:Guys and St. Thomas' NHS Trust: Honoraria. Offidani:Celgene: Honoraria, Research Funding; Janssen: Honoraria. Bridoux:Celgene, Roche, Amgen, Janssen, Baxte: Honoraria, Research Funding. de la Rubia:Janssen: Consultancy; Amgen,: Consultancy; Celgene: Consultancy; Bristol Myers: Consultancy. Kueenburg:Celgene International Sarl: Consultancy, Honoraria. Lersch:Celgene: Employment. Bacon:Celgene: Employment, Equity Ownership. 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.

Description: Background: This EU PASS is an observational, non-interventional registry designed to characterize the safety profile of pomalidomide (POM) in the treatment of RRMM in a real-world setting. Objectives:To assess the incidence of adverse events (AEs) of special interest, including neutropenia, thrombocytopenia, venous thromboembolism, peripheral neuropathy, and second primary malignancies in patients (pts) with RRMM treated with POM according to current clinical practice. Methods: Pts with symptomatic RRMM were enrolled at the investigator's discretion and after the decision was made to treat with POM. Thromboprophylaxis was administered per local standard practice. AEs were graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (version 4). The study is ongoing and open for recruitment in centers across Europe. Results: As of June 2016, 218 pts across 100 institutions in 8 European countries were included in the safety population. At the time of this abstract, 153 pts (70.2%) were ongoing. Median age was 68 yrs (range, 37-88 yrs), with 39.9% of pts 〈 65 yrs, 32.6% between 65 and 75 yrs, and 27.5% ≥ 75 yrs; 56.9% were male. Median time from diagnosis was 4.7 yrs (range, 0.4-25.4 yrs). Median number of prior therapies was 3 (range, 0-10); 80.8% of pts had at least 3 prior lines. Most pts (95%) received prior lenalidomide (given in second line in 66.1% and in third line in 20.2%). Prior bortezomib was administered in 96.8% of pts (given in second line in 54.6% and in third line in 28.4%). Almost half of the pts (49.5%) had a good performance status (Eastern Cooperative Oncology Group performance status 0-1). In this analysis, median treatment duration was 12.9 wks (range, 0.7-87.9 wks). Overall, 50.9% of pts (n = 111) had grade 3-4 AEs. AEs of all grades occurred in 79.8% (n = 174). Neutropenia of all grades was only reported in 22% of pts (n = 48), and febrile neutropenia in 2.3% of pts (n = 5). Infections of all grades occurred in 44.5% of pts (n = 97); of those, 11.5% were pneumonia. Thrombocytopenia occurred in 7.8% (n = 17). Fatigue occurred frequently in 13.8% of pts (n = 30). There were some gastrointestinal disorders, such as diarrhea in 7.8% (n = 17), constipation in 6.4% (n = 14), and nausea in 6.0% (n = 13) of pts. Peripheral polyneuropathy was uncommon (3.2%; n = 8). Acute myocardial infarction and deep vein thrombosis were observed in 1 pt each, and 1 pt developed basal cell carcinoma. Conclusions: Results of this ongoing non-interventional study in RRMM on the use of POM in the real-world setting show a similar AE profile to that in the pivotal trial published by San Miguel in Lancet Oncology (2013). POM was generally well tolerated, and the overall safety profile is similar to that seen in pivotal trials. Updated data will be presented at the meeting. Disclosures Di Raimondo: ARIAD; Bristol-Myers Squibb; Novartis; Roche: Consultancy; Bristol-Myers Squibb; Celgene; Novartis: Speakers Bureau; Gilead Sciences: Other: Travel Expenses. Bentsen:Celgene, Teva: Other: Travel expenses. Kueenburg:Celgene International Sarl: Consultancy, Honoraria. Lersch:Celgene: Employment. Bacon:Celgene: Employment, Equity Ownership. Plesner:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Description: Abstract 1867 Background: In recent years, there have been major advances in the treatment of multiple myeloma (MM) as patients now have treatment options that greatly improve clinical outcomes. Many publications have described the safety of anti-myeloma drugs in the clinical trial setting. However, very few have addressed the issue of tolerability of these agents in a real-world clinical setting. Lenalidomide is an effective treatment option for MM and is currently approved by the EMA and US FDA for the treatment of MM patients who have received at least 1 prior therapy. Here we analyze the tolerability of 3 common novel agent-based anti-myeloma therapies in daily clinical practice. Methods: This observational post-authorization safety study was designed to characterize the safety profile of lenalidomide and to compare the incidence of adverse events (AE) with those occurring in patients receiving other anti-myeloma treatments. Patients entering the study had previously received at least 1 prior therapy and were commencing a new treatment for their relapsed/refractory MM (RRMM). Patients were enrolled into the Lenalidomide Cohort (lenalidomide plus dexamethasone) or the Background Cohort (all other treatments) based on investigator's discretion. Thromboprophylaxis was allowed, but not required. Results: As of July 2011, 2201 RRMM patients in 265 institutions in 17 European countries were enrolled. 1500 received lenalidomide, 538 bortezomib, 90 thalidomide, and 73 received other therapies or had missing data. 75 patients from the Background Cohort crossed over to receive lenalidomide. Median follow-up was 20.7 weeks (range, 0.1–125.7 weeks). Overall, the median age was 69 years (range, 29–92) and 55% were male. Most patients had a good performance status (ECOG 0–1) but 18% had an ECOG score of 2–4. The median number of previous treatment lines was 2 (1–6), 51.5% had 2 previous lines and 24% had 3 or more. Baseline characteristics across treatment groups were similar. Patients receiving lenalidomide had a median treatment duration of 4.4 months; patients receiving bortezomib and thalidomide had 3.4 months and 3.7 months, respectively. NCI grade 3/4, serious and life threatening AEs are presented in the table. Venous thromboembolism was experienced in 5% of lenalidomide-treated patients (3% had grade 3/4); 0.7% of bortezomib-treated patients (0.6% had grade 3/4); 1 (1%) thalidomide-treated patient had grade 3/4. Peripheral neuropathy was observed in 10% of lenalidomide-treated patients (1% had grade 3/4); 28% of bortezomib-treated patients (4% had grade 3/4); and 21% of thalidomide-treated patients (2% had grade 3/4). Ten (0.5%) invasive second primary malignancies (SPM) were reported across all treatment groups; 5/1500 (0.3%) patients treated with lenalidomide, 4/538 (0.7%) with bortezomib, and 1/90 (1%) with thalidomide. Three cases of second primary hematologic malignancies (lenalidomide, 2; bortezomib, 1; thalidomide, none) and 7 cases of second primary solid tumors (lenalidomide, 3; bortezomib, 3; thalidomide, 1) were observed. Additionally in the lenalidomide group, 1 patient each developed a non-invasive basal cell carcinoma and a non-invasive fibrous histiocytoma. All of these patients were heavily pre-treated and most had received autologous stem cell transplantation to support high-dose melphalan during the course of their disease. 51% of patients in the lenalidomide group discontinued therapy while 65% and 71% discontinued bortezomib and thalidomide treatments, respectively. Primary reasons for discontinuation were adverse events (lenalidomide, 13%; bortezomib, 14%; thalidomide, 18%) and disease progression (lenalidomide, 15%; bortezomib, 13%; thalidomide, 17%). Overall, 1% of patients died due to an adverse event suspected to be related to drug (lenalidomide, 1%; bortezomib, 0%; thalidomide, 1%). Conclusion: Consistent with previous reports, lenalidomide is generally well tolerated. With the exception of peripheral neuropathy, adverse events in this group of patients treated in daily clinical practice appeared similar across treatment groups. Disclosures: Cavo: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees. Symeonidis:Novartis Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene Corporation: Consultancy, Research Funding; Genzyme: Research Funding; Pfizer: Research Funding; Gilead: Consultancy, Research Funding. Bird:Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Genzyme: Membership on an entity's Board of Directors or advisory committees. Bacon:Celgene Corporation: Employment. Rosettani:Celgene Corporation: Employment. Kueenburg:Celgene Corporation: Employment. Minton:Celgene Corporation: Employment, Equity Ownership.