ALBERT

Description: Background Ixazomib, the first oral proteasome inhibitor, has been approved for 〉3 years in 〉70 countries, for the treatment of RRMM pts who have received ≥1 prior therapy, on the basis of the TOURMALINE-MM1 study, which reported an overall response rate (ORR) of 78% and median progression free survival (PFS) of 20.6 mos. Although outcomes and tolerability in routine clinical practice often differ from data reported in clinical trials, growing evidence suggest that outcomes in patients treated with ixazomib-based regimens are comparable to those in the Phase 3 TOURMALINE-MM1 trial. We report on an expanded pooled analysis with longer follow-up of IRd therapy from the INSIGHT MM study (NCT02761187) and the Czech Registry of Monoclonal Gammopathies (RMG) to evaluate the effectiveness of IRd in RRMM pts in routine clinical practice. Methods INSIGHT MM is a large, prospective, observational study which has enrolled over 4,200 adult pts with MM from Europe (plus Israel, EUR), the US, Asia, and Latin America, with a planned follow-up of ≥5 years. The RMG comprises clinical data for 〉6,000 MM pts enrolled at 19 Czech and 4 Slovak centers. Eligible pts had 1-3 (INSIGHT) or ≥1 prior therapy (RMG) including an IR-based regimen. Individual pt level data on demographics, disease characteristics, treatment history, effectiveness, and safety from INSIGHT and RMG were integrated and analyzed. Best response or time to first response and PFS were determined as per investigator assessment, using IMWG criteria. PFS, duration of treatment (DOT), and overall survival (OS) were estimated using Kaplan Meier (KM) methodology, applying an exclusion criterion to account for immortal time bias (INSIGHT only). Results At data cutoff of 22 Nov 2018, 217 pts (83 in INSIGHT and 134 in RMG) from 11 countries had been included: 191 (88%) from EUR, 17 (8%) from the US, and 9 (4%) from Taiwan; 89% of pts were treated in an academic facility. At diagnosis, 32% of pts had ISS Stage III disease, 78% had bone lesions, 46% had anemia, and 12% had elevated creatinine. At study start, median age was 67 years with 12% 〉75 years; 58%/14% of pts had ECOG performance status 1/2. The distribution of immunoglobulin (Ig) heavy and light chain MM was as expected; 69% of pts had IgG MM. Overall, 21% of pts had extramedullary disease. Prior therapies included: bortezomib (90%), stem cell transplant (60%), thalidomide (47%), lenalidomide (26%), carfilzomib (8%), daratumumab (6%), and pomalidomide (2%). Median time from diagnosis to start of IRd therapy was 42.1 mos; 43%/35%/22% of pts received IRd at 2nd/3rd/≥4th line. The most common reasons for starting IRd were relapse/progression (87%) and insufficient response (10%). The most common CRAB criteria present were bone lesions (48%) and anemia (18%). Median duration of follow-up was 12.6 mos in all pts. At data cutoff, 117 (54%) pts had discontinued IRd; median DOT was 11.9 (95% CI: 9.4-15.2) mos; at 12 mos, 49% (41.3-56.2) of pts were still on treatment (KM estimates). Data on best response to therapy were available for 152 pts. The ORR was 74%, with 36% ≥VGPR; ORR with IRd at 2nd/3rd/ ≥4th-line therapy was 82%/71%/59%, including 43%/37%/17% ≥VGPR. Median time to first response was 1.2 mos (RMG); median time to best response was 3.7 mos (INSIGHT). Median PFS was 21.6 (95% CI: 13.6-26.7) mos across all lines. PFS rate at 12 mos was 62%, and 86 (40%) pts had progressed at data cutoff. Median time to next therapy (TTNT) was 31.5 (95% CI: 24.5-35.9) mos, with a 12-month rate of 74% across all lines. Overall, 60 (28%) pts received subsequent therapies including daratumumab (22%), pomalidomide (22%), bortezomib (20%), carfilzomib (17%), lenalidomide (15%), and thalidomide (12%). At data cutoff, 53 (24%) pts had died. Median OS was 36.7 (95% CI: 24.4-NR) mos, with 79% of pts alive at 12 mos (Figure). Regarding safety, ixazomib and lenalidomide dose reductions were required in 16% and 36% of pts, respectively, including 10% and 21% who required dose reductions due to AEs. Conclusions These findings show that the effectiveness of IRd in routine clinical practice (ORR 74%, median PFS 21.6 mos) is comparable to the efficacy of IRd reported in the registrational TOURMALINE MM1 trial (ORR 78%, median PFS 20.6 mos). IRd is well tolerated with no new safety signals, and low rates of dose reductions due to AEs for ixazomib (10%) and lenalidomide (21%). Outcomes should be interpreted with caution due to limited maturity of data. Disclosures Hajek: Janssen: Honoraria, Other: Consultant or advisory relationship, Research Funding; Amgen: Honoraria, Other: Consultant or advisory relationship, Research Funding; Celgene: Honoraria, Other: Consultant or advisory relationship, Research Funding; AbbVie: Other: Consultant or advisory relationship; Bristol-Myers Squibb: Honoraria, Other: Consultant or advisory relationship, Research Funding; Novartis: Other: Consultant or advisory relationship, Research Funding; PharmaMar: Honoraria, Other: Consultant or advisory relationship; Takeda: Honoraria, Other: Consultant or advisory relationship, Research Funding. Minarik:Celgene: Consultancy, Honoraria, Research Funding; Amgen, BMS, Janssen-Cilag, Takeda: Consultancy, Honoraria. Straub:Amgen, Takeda, Celgene: Consultancy. Berdeja:Amgen Inc, BioClinica, Celgene Corporation, CRISPR Therapeutics, Bristol-Myers Squibb Company, Janssen Biotech Inc, Karyopharm Therapeutics, Kite Pharma Inc, Prothena, Servier, Takeda Oncology: Consultancy; AbbVie Inc, Amgen Inc, Acetylon Pharmaceuticals Inc, Bluebird Bio, Bristol-Myers Squibb Company, Celgene Corporation, Constellation Pharma, Curis Inc, Genentech, Glenmark Pharmaceuticals, Janssen Biotech Inc, Kesios Therapeutics, Lilly, Novartis, Poseida: Research Funding; Poseida: Research Funding. Boccadoro:AbbVie: Honoraria; Mundipharma: Research Funding; Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Spencer:AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Haemalogix: 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, Research Funding, Speakers Bureau; Secura Bio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Specialised Therapeutics Australia: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. van Rhee:Karyopharm Therapeutics: Consultancy; Kite Pharma: Consultancy; Adicet Bio: Consultancy; EUSA: Consultancy; Castleman Disease Collaborative Network: Consultancy; Takeda: Consultancy; Sanofi Genzyme: Consultancy. Thompson:Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; VIA Oncology: Membership on an entity's Board of Directors or advisory committees; Adaptive: Membership on an entity's Board of Directors or advisory committees; UpToDate: Patents & Royalties: Myeloma reviewer; GSK: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Doximity: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; AbbVie: Research Funding; BMS: Research Funding; Lynx Bio: Research Funding. Abonour:BMS: Consultancy; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Chari:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncoceutics: Research Funding; Novartis Pharmaceuticals: Research Funding; GlaxoSmithKline: Research Funding; Array Biopharma: Research Funding; Karyopharm: 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, Research Funding; Millennium/Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy; Pharmacyclics: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees. Cook:Karyopharm: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Costello:Takeda: Honoraria, Research Funding; Janssen: Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Davies:Amgen, Celgene, Janssen, Oncopeptides, Roche, Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Consultant/Advisor; Janssen, Celgene: Other: Research Grant, Research Funding. Hungria:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: 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, Speakers Bureau. Lee:Amgen: Consultancy, Research Funding; GlaxoSmithKline plc: Research Funding; Sanofi: Consultancy; Daiichi Sankyo: Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Leleu:Sanofi: Honoraria; Takeda: Honoraria; Oncopeptide: Honoraria; Karyopharm: Honoraria; Amgen: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Merck: Honoraria. Puig:Takeda: Consultancy, Honoraria; The Binding Site: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Rifkin:Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Terpos:Celgene: Honoraria; Takeda: Honoraria, Other: Travel expenses, Research Funding; Medison: Honoraria; Janssen: Honoraria, Other: Travel expenses, Research Funding; Amgen: Honoraria, Research Funding; Genesis: Honoraria, Other: Travel expenses, Research Funding. Usmani:Bristol-Myers Squibb: Consultancy, Research Funding; Sanofi: Patents & Royalties, Research Funding, Speakers Bureau; Janssen: Consultancy, Patents & Royalties, Research Funding, Speakers Bureau; Takeda: Consultancy, Patents & Royalties, Research Funding, Speakers Bureau; Celgene: Consultancy, Patents & Royalties, Research Funding, Speakers Bureau; Merck: Consultancy, Research Funding; Pharmacyclics: Patents & Royalties, Research Funding; Amgen: Consultancy, Patents & Royalties, Research Funding, Speakers Bureau; Array Biopharma: Patents & Royalties, Research Funding; Skyline DX: Consultancy. Weisel:Sanofi: Consultancy, Honoraria, Research Funding; Juno: Consultancy; GSK: Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene Corporation: Consultancy, Honoraria, Research Funding; Adaptive Biotech: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding. Zonder:Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Intellia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Caelum: Consultancy, Membership on an entity's Board of Directors or advisory committees; Alnylam: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees. Skacel:Millennium Pharmaceuticals, Inc., subsidiary of Takeda Pharmaceutical Company Limited: Employment. Elliott:Takeda: Employment. Demers:Takeda: Employment. Stull:Takeda: Employment. Ren:Takeda: Employment. Maisnar:Janssen, Amgen, Celgene, Takeda, BMS: Consultancy, Honoraria.

Description: Background: The patients with multiple myeloma (MM) have an increased risk of venous thromboembolism (VTE), particularly during the induction phase of therapy. Low molecular weight heparins (LMWH) seem to be useful for thromboprophylaxis in these patients. We analyzed prophylactic efficiency of LMWH based on dose either lower or higher than 70 IU/kg of body weight. Patients and Methods: 223 patients with newly diagnosed MM were treated with induction chemotherapy consisting of vincristine, doxorubicin and dexamethasone (VAD) or vincristine, idarubicin and dexamethasone (VID) as a part of multicenter CMG 2002 trial. The first cohort of 137 patients received no systematic thromboprophylaxis. After a high incidence of thrombotic complications has been reported, the thromboprophylaxis with different doses of LMWHs was used in 86 consecutive patients for 4 months of induction therapy. Finally, 101 patients enrolled to the CMG 2002 trial in single centre were analyzed retrospectively, based on dose either lower or higher than 70 IU/kg of body weight. From this 101 patients 34% (34/101) received no systematic thromboprophylaxis, 38% (39/101) received LMWH (dalteparin) daily dose lower than 70 IU/kg, and 28% (28/101) received LMWHs daily dose higher than 70 IU/kg. The efficacy and safety of this treatment were analyzed. The chi-square test was used for statistical analysis. Results: Incidence of VTE was significantly reduced in the group of 86 patients receiving the recommended thromboprophylaxis, as compared to 137 patients without prophylaxis (1.2% vs. 12.4%, p=0.003, risk reduction 11.25%). Single centre analysis showed that no VTE was developed in the group of 28 patients receiving more than 70 IU/kg of LMWH daily. It was significantly different from the 34 patients without prophylaxis (0% vs. 15%, p=0.002). The incidence of VTE in 39 patients with LMWHs daily dose lower than 70 IU/kg was reduced to 7.6%, which is still clinicaly significant as compared to cohort of 28 patients receiving more than 70 IU/kg of LMWH daily (0% vs. 7.6%, p=0.05). No case of major bleeding was developed in any group. Conclusions: Thromboprophylaxis with LMWHs is effective in patients with newly diagnosed multiple myeloma during the induction chemotherapy only if the LMWH dose is sufficient. Our date shown that minimal sufficient dose seems to be more than 70 IU/kg of LMWH daily, as in this cohort of patients no case of VTE was developed.

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

Description: Introduction: Multiple myeloma is one of the most frequent hematological malignancies. The prognosis of patients has substantially improved due to new treatment options. However, the early diagnosis is still a crucial factor for prognosis. First symptoms of myeloma are different and mostly unspecific - therefore many patients are diagnosed late with serious organ and/or tissue damage. Czech Myeloma Group initiated the program for early diagnosis of MM in 2007. Program (named due to educational reasons„CRAB“) was focused on general practitioners (GPs) and key specialists responsible for recognizing the symptoms related to MM (neurology, orthopedics, nephrology). We present results of the final analysis. Methods: a/ telephonic survey for healthcare professionals, b/ written information for primary care providers, c/ brochures containing definition of clinical symptoms and recommended diagnostic methods, d/ patient questionnaire, e/ presentations at medical meetings in Czech republic, f/ presentation in non-hematological medical journals, g/ e-learning. Primary objectives were: 1) decrease risk of late diagnosis ( 〉 3 month after first symptoms of myeloma) from 50% to 30% , 2) reduction of irreversible deterioration at the time of diagnosis from 20% to

Description: Background : Recent improvements in the treatment of relapsed-refractory multiple myeloma (RRMM) have significantly increased the survival of patients. Despite the availability of new therapies, only 20-30% of the RRMM patients respond to any particular treatment and new approaches are clearly needed. Melflufen is an alkylating peptide belonging to Peptidase Enhanced Compounds (PEnCs) targeting the multiple myeloma (MM) transformation process through aminopeptidase potentiation of the compound; aminopeptidases are heavily over-expressed in MM cells and involved in tumor migration, cell proliferation and angiogenesis. Melflufen selectively targets MM cells through aminopeptidase-driven accumulation, leading to a 50-fold enrichment of alkylating metabolites. The enrichment results in selective cytotoxicity (increased on-target cell potency and decreased off-target cell toxicity), overcomes resistance pathways of existing myeloma treatments (including alkylators) and demonstrates strong anti-angiogenic properties. Melflufen in combination with dexamethasone (dex) has shown promising activity with an acceptable safety profile. The OP-104 ANCHOR phase 1/2 study was designed to evaluate melflufen and dex in triplet-combination, with either bortezomib or daratumumab in RRMM patients. Preliminary results of the phase I part are reported below. Methods: Patients must have RRMM as defined by refractory (or intolerant) to an immunomodulatory agent (IMiD) or a proteasome inhibitor (PI). In combination with bortezomib, patients cannot be refractory to a PI and in combination with daratumumab patients cannot be previously exposed to any antiCD-38 mAb. Patients must have measurable disease and a maximum of 4 prior lines of therapy. Patients will be treated until documented disease progression or unacceptable toxicity (NCT03481556). The primary objective of phase 1 is to determine the optimal dose of melflufen, up to a maximum of 40 mg, in combination with bortezomib and dex or daratumumab and dex. An additional 20 patients per regimen will be recruited in the phase 2 part of the study where the primary objective is ORR (investigator assessed according to IMWG criteria). Up to three dose levels of melflufen (30, 40 or 20 mg) are being tested. Melflufen is given i.v. on Day 1 of each 28-day cycle in 2 different combinations. Regimen A, in combination with subcutaneous bortezomib at 1.3 mg/m2 Days 1, 4, 8 and 11, and 20 mg dex Days 1, 4, 8 and 11, and 40 mg dex Days 15 and 22. Regimen B, in combination with 16 mg/kg daratumumab weekly for 8 doses, every 2 weeks for 8 doses and then every 4 weeks, as well as 40 mg weekly dex. Regimen selection is investigators' choice based on prior therapy. Results: As of July 18th 2018, 8 patients were enrolled to the study. Two patients in regimen A at 30 mg melflufen, and 6 patients in regimen B, 3 patients at 30 mg melflufen and 3 at 40 mg melflufen. In regimen A (in combination with bortezomib), the 2 patients treated were 81 and 82 years respectively, had received 4 and 2 prior lines of treatment with 5.6 and 6.9 years since diagnosis respectively. A total of 4 cycles were available for safety evaluation. 30 mg melflufen was well tolerated with no reported DLTs. One patient experienced a grade 3 (G3) neutropenia. After one cycle of treatment, 1 patient achieved an MR and 1 patient achieved SD. In regimen B (in combination with daratumumab), median age was 56 years, median number of prior lines was 2 (1-3) and median years since diagnosis was 2.3 years. A total of 9 cycles were available for safety evaluation in 3 patients at 30 mg melflufen. 30 mg melflufen was well tolerated with no reported DLTs. Two patients experienced treatment-related G3 neutropenia. After one cycle of treatment, the 3 patients treated with melflufen 30 mg achieved PR, MR and MR. All patients are ongoing. Safety and efficacy for melflufen 40 mg dose level has not been evaluated yet. The study is ongoing and updated results on the phase 1 trial will be presented at the meeting. Conclusion: Combining melflufen with bortezomib or daratumumab seems feasible, and well tolerated with no DLT in the melflufen 30 mg cohorts. Early signs of activity are seen after only 1 cycle of therapy. Updated results on the phase 1 trial will be presented at the meeting. Disclosures Granell: Janssen: Honoraria; Celgene: Honoraria. Hajek:Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. Oriol:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Karlin:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support. Maisnar:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Martinez Lopez:BMS: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Jansen: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau. Mateos:Celgene: 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; 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; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: 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; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Ribrag:MSD: Honoraria; Infinity: Consultancy, Honoraria; epizyme: Consultancy, Honoraria; argenX: Research Funding; Gilead: Consultancy, Honoraria; Roche: Honoraria, Other: travel; Servier: Consultancy, Honoraria; NanoString Technologies: Consultancy, Honoraria; Amgen: Research Funding; pharmamar: Other: travel; BMS: Consultancy, Honoraria, Other: travel; Incyte Corporation: Consultancy. Richardson:BMS: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees. Byrne:Takeda: Consultancy; Oncopeptides AB: Consultancy, Other: Stock Options. Jacques:Oncopeptides AB: Consultancy, Other: Stock Options. Zubair:Oncopeptides AB: Employment, Other: Stock Options. Ocio:Array Pharmaceuticals: Research Funding; Novartis: Consultancy, Honoraria; Mundipharma: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Sanofi: Research Funding; Takeda: Consultancy, Honoraria; BMS: Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy; Pharmamar: Consultancy; Seattle Genetics: Consultancy.

Description: Introduction: Multiple myeloma patients over the age of 65 represent the majority of myeloma population. The main goal was to evaluate treatment outcomes in terms of overall survival for elderly patients based on initial choice of anti-myeloma drugs, and to find potential factors affecting survival. Patients and Methods: This is a retrospective registry based analysis from the Registry of monoclonal gammopathies of the Czech Myeloma Group. Patients with multiple myeloma diagnosed between 2007-2016 over the age of 65 with symptomatic myeloma were included in the analysis. Basic demographic data and disease characteristics were obtained. The Kaplan-Meier estimates were completed by the Greenwood confidence interval. The log-rank test was used to estimate the statistical significance of the difference between the curves. The Cox proportional hazards model was performed to explore the univariate significance of risk factors. Results: Data from 1410 MM patients were obtained. Gender [HR 1.316 (1.124-1.541), p=0.001], age [above 75 vs. 66-75, HR 1.437 (1.221-1.692), p〈 0.001], creatinine levels [at cutoff 152 µmol/L, HR 1.613 (1.365-1.905), p〈 0.001] and ECOG performance status [0-1 vs. 2-4, 1.869 (1.594-2.191), p〈 0.001] were found to significantly affect overall survival. Moreover these risk factors have cumulative effect on overall survival of the patients. Overall survival of patients regardless to above mentioned risk factors treated with upfront bortezomib (N = 880) was median OS 40.4 months (CI: 36.1-44.7), patients treated with upfront thalidomide (N = 370) had median OS 48.1 months (CI: 41.0-55.2), for lenalidomide (N = 64) median overall survival was 53.2 months (CI: 44.6-61.8) and for combination of bortezomib and thalidomide (N = 46) 32.2 months (CI: 26.6-37.8). When any of these risk factors was present the OS in each group shortened. In the group of patients with no risk factors (N = 255) the median OS for bortezomib (N = 126) was not reached, for thalidomide (N = 96) the median OS was 66.3 months (CI: 43.1-89.6), for lenalidomide (N = 17) 71.1 months (CI: 44.8-97.4) and for combination of bortezomib and thalidomide (N=8) was not reached. In the group of patients with 1 risk factor (N = 514) the median OS for bortezomib (N = 303) was 46.1 months (CI: 36.2-56.1), for thalidomide (N = 141) 56.2 months (CI: 47.5-64.9), for lenalidomide (N = 29) 49.0 months (CI: 9.7-88.2) and for combination of bortezomib and thalidomide (N=20) was not reached. In the group of patients with 2 risk factors (N = 420) the median OS for bortezomib (N = 288) was 34.0 months (CI: 24.7-43.4), for thalidomide (N = 87) 31.9 months (CI: 22.8-40.9), for lenalidomide (N = 14) 33.2 months (CI: 0.0-67.6) and for combination of bortezomib and thalidomide (N=20) 29.4 months (CI: 7.6-51.1). In the group of patients with 3-4 risk factors (N = 221) the median OS for bortezomib (N = 163) was 19.2 months (CI: 14.9-23.5), for thalidomide (N = 46) 18.9 months (CI: 13.0-24.7), for lenalidomide (N = 4) 6.1 months (CI: 0.0-63.0) and for combination of bortezomib and thalidomide (N=3) 14.3 months (CI:-). Conclusion: The overall survival of patients above the age of 65 shows promising results with the use of novel agents. The treatment outcomes seem to be generally affected by overall condition, age and gender of the patient rather than treatment modality used upfront. Figure. Figure. Disclosures Hajek: Amgen: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Research Funding. Maisnar:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees.

Description: Aims: Treatment of multiple myeloma (MM) in relapsed and refractory setting (RRMM) has been a challenge. The best outcomes have been observed in triplet combination of novel drugs. However, most combinations require weekly parenteral administration thus degrading patients´adherence to therapy, especially when treatment is scheduled "until progression". The introduction of fully oral triplet combination ixazomib, lenalidomide and dexamethasone (IRD) showed an outstanding efficacy in the Tourmaline-MM1 trial. Our aim is to determine the efficacy and safety of IRD regimen outside clinical trials. Patients and methods: A cohort of 127 RRMM patients from the Czech and Slovak Republic were treated with IRD regimen within a Named Patient Program between 2016 and 2018. The M/F ratio was 1.2:1 with median age 66 years (41-84). The representation of M-protein and light chain types as well as ISS stage was standard. The data for cytogenetics were recorded only at the time of diagnosis in 71% of patients with 15 patients having high-risk features - t(4;14), t(14;16) and del17, and 41 patients having standard risk features. In 34 patients we were not able to determine the risk status as at least one abnormality was missing and none was positive. The presence of extramedullary plasmocytoma was recorded in 15% of patients. Most patients received IRD for their 1st relapse (58.5%), followed by 2nd (23.7%) and 3rd relapse (7.6%) with significant portion of patients being treated in ≥4th relapse (10.1%). The pretreatment with individual drugs was as follows: bortezomib (BTZ) 94.5%, thalidomide (THAL) 40.9%, lenalidomide (LEN) 18.9% and carfilzomib 5.5%. 62.2% of patients underwent previous autologous stem cell transplant. Altogether 25.2% of patients were refractory to at least 1 drug with 18.9% being BTZ refractory and 7.9% LEN refractory. Data were analyzed from the Czech Registry of Monoclonal Gammopathies. Data were described by absolute and relative frequencies of categorical variables and mean (standard deviation), median (minimum-maximum) of quantitative variables. Survival measures were plotted using Kaplan-Meier methodology at 95% confidence interval, log-rank test was used to estimate the statistical significance at P

Description: Background : Outcomes reported in real-world practice versus controlled clinical trials show markedly shorter treatment durations, progression free survival (PFS) and overall survival (OS). Understanding effectiveness of therapeutic regimens in routine practice is critical for treating physicians as well as for regulatory and reimbursement authorities. We have performed a real-world comparison of two regimens, ixazomib, lenalidomide and dexamethasone (IRD) triplet and lenalidomide and dexamethasone (Rd) doublet in patients with relapsed and/or refractory multiple myeloma (RRMM) treated in seven Czech and one Slovak hematology-oncology centers. Patients and methods: Between 3/2015 and 5/2017, 344 patients with RRMM were treated with either IRD (N=127) or RD (N=217). Patients selected for both cohorts had the same inclusion and exclusion criteria. Patient baseline characteristics were well balanced. The data were collected through the Czech Registry of Monoclonal Gammopathies (RMG), which is an international database gathering data from patients with monoclonal gammopathies within Central Europe. Results: The median follow-up in the IRD vs RD arm was 20.8 vs 15.5 months, respectively. Median PFS in pts with 1-3 prior lines for the IRD cohort was 23.1 months (95% CI 11.8-34.5 months) and 11.6 months (95% CI 8.4-11.8 months) for the RD cohort favoring the all-oral triplet (p=0.001). The median PFS for all patients including 4+ line of therapy was 17.5 months (95% CI 10.3-24.7) in the IRD cohort versus 11.5 months (95% CI 8.6-14.3) in the RD group (p=0.005). Median OS for pts with 1-3 prior lines for IRD cohort was not reached, and was 27.1 months (95% CI 23.1-31.1 months) in the RD cohort (p=0.002). Median OS for all patients, including 4+ lines of treatment was 36.6 months in the IRD vs 26.0 months in the RD cohort (p=0.008). The PFS benefit of IRD over RD was observed in most of the assessed subgroups; in younger pts ≤65 years with hazard ratio (HR) 0.58, in pts 66-75 years HR 0.64. There was a trend towards better PFS in patients with lower ISS stage; ISS1 HR 0.53, ISS2 HR 0.58 and ISS3 the HR was 0.87. Patients in the 1st relapse (HR 0.53) benefited most from the IRD, followed by the 2nd relapse (HR 0.58), 3rd relapse (HR 0.90) and pts relapsing after 4+ therapies (HR 0.88). The PFS benefit of IRD regimen was observed in pts regardless of previous stem cell transplantation; transplant-eligible patients HR 0.51 and transplant-ineligible HR 0.71. Patients who did not benefit from the triplet regimen were those over 75 years of age and pts with the presence of extramedullary disease. The IRD treatment was well tolerated. The safety profile was concordant with previously reported data. Conclusions: This RMG comparative cohort analysis shows PFS benefit of all-oral IRD regimen over RD in the real world setting, and confirms growing evidence that long term outcomes with IRD triplet are comparable with phase 3 TOURMALINE-MM1 trial. Our analysis also shows an overall survival benefit of IRD over RD treatment. Patients older than 75 years, with 4+ lines of therapy and presence of extramedullary disease did not profit from addition of ixazomib to RD doublet.Additional data with larger patient populations confirming RWE effectiveness are warranted. With support of AZV 17-29343A, NV18-03-00500, FNOl 00098892, IGA-LF-2019-001, PROGRES Q40/08, MH CZ-DRO (UHHK, 00179906) Disclosures Minarik: Celgene: Consultancy, Honoraria, Research Funding; Amgen, BMS, Janssen-Cilag, Takeda: Consultancy, Honoraria. Straub:Amgen, Takeda, Celgene: Consultancy. Spicka:Celgene: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Sanofi: Consultancy; Takeda: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Sanofi: Consultancy. Skacel:Millennium Pharmaceuticals, Inc., subsidiary of Takeda Pharmaceutical Company Limited: Employment. Maisnar:Janssen, Amgen, Celgene, Takeda, BMS: Consultancy, Honoraria.