Lenalidomide Maintenance Does Not Negatively Impact Overall and Progression Free Survival Using Lenalidomide-Based Regimens for Multiple Myeloma in First Relapse

Abstract BACKGROUND Outcomes in multiple myeloma have improved dramatically over the last decade however, optimal sequencing of therapy remains unknown. Specifically, in an era where post-transplant lenalidomide (L) maintenance is now as established standard of care, questions remain around the utility of full dose L-based regimens in second line therapy. In this series, we sought to evaluate the impact of different regimens used at first relapse in patients who received autologous stem cell transplant (ASCT) in the frontline setting treated with and without lenalidomide maintenance (LM). We focused on the impact of L-based therapies in patients relapsing on LM. METHODS Using our prospectively maintained institutional MM database we retrospectively analyzed patients treated at the Cross Cancer Institute from January, 2005 to January, 2016 to ensure 2 years of follow-up for surviving patients. 4 categories were identified based on 2 variables: receipt of LM following 1st line therapy (yes or no) and receipt of L-based 2nd line therapy (yes or no). The primary endpoint was 2nd PFS defined as time of initiation of second line therapy to relapse, death or last follow-up. OS was defined as time of initiation of first line induction therapy to death or last follow-up. Second OS was defined as time of initiation of second line therapy to death or last follow-up. Survival statistics were determined using the Kaplan-Meier method with SPSS software. A p - value of <0.05 was considered significant. RESULTS 213 patients received standard bortezomib-based induction and ASCT of which 132 (62%) received LM. Median follow up for the LM patients was 48 months compared to 74.6 months in non-LM patients. 103 patients (48%) required treatment with second line therapy. Forty-four percent patients were treated with LM while 56% were not. Sixty-nine percent received L-based therapy at relapse, 21% received PI-based therapy and 8% were treated with a PI-IMID combination (table 1). Focusing on the cohort of relapsed patients who received LM (n=44), the median 2nd PFS was 9.3 months in those that received L-based second line therapy vs 4.1 months in those that did not (p = 0.28, figure 1b]. In patients who did not receive LM (n = 55) the median 2nd PFS was 14.0 months in those who received L-based second line therapy vs 6.9 months in those who did not (p = 0.19, figure 1a. Examining all patients who received L-based therapy at relapse there was no difference in 2nd PFS based on whether LM was given (p = 0.42). The median 2nd OS was not statistically significant between the groups (p = 0.39, figure 1b. Patients on LM had a median 2nd OS of 34 months with L-based therapy at relapse compared to 39.2 months without. The median 2nd OS in non-LM patients was 34.5 months in those receiving L-based therapy at first relapse and 23.4 months in those that did not (p=0.10). There was no statistically significant differences in median OS between the 4 groups (p = 0.83). For patients who received LM the median OS was not reached in those receiving L-based therapies at relapse and was 78.1 months in patients who did not. In patients who did not receive LM the median OS was 78.0 months in those receiving L-based therapies at relapse and 69.3 months in those who did not. CONCLUSION Our data suggests that receiving LM does not negatively impact survival outcomes after receiving full dose L-based therapy at relapse. Both median 2nd PFS and 2nd OS were similar with L-based therapies regardless of prior LM. While the 2nd PFS at relapse does fall short of recently published trials in relapsed MM there are some notable confounders here. Firstly, this real-world data includes frailer patients with potentially greater co-morbidities possibly influencing choice and duration of therapy as well as reflect more aggressive disease biology. Secondly, given the relatively short median follow-up of the relapsed LM patients to date, the cohort may be enriched with "early" relapsers (< 2-years) also potentially indicative of biologically more aggressive disease. As such, this may underestimate the true impact of L-based therapies in patients relapsing on LM. Larger series with longer follow-up are necessary to formally examine whether multi-agent L-based regimens confer additional benefit over L-Dexamethasone or non-L based regimens. Real world registries will be useful as prospective trials are unlikely to be done. Disclosures Sandhu: Novartis: Honoraria; Bioverativ: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Venner:Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Takeda: Honoraria.

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Real-World Outcomes for Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Lenalidomide, Bortezomib, and Dexamethasone, or Bortezomib and Dexamethasone: An Enhanced Electronic Health Records Database Analysis

Blood ◽

10.1182/blood-2018-99-111121 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2243-2243

Author(s):

Ajai Chari ◽

Brian Ung ◽

Marc Tian ◽

Amit Agarwal ◽

Kejal Parikh

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Real World ◽

Research Funding ◽

Second Line ◽

Second Line Therapy ◽

Employment Equity ◽

Advisory Committees ◽

Line Therapy ◽

Equity Ownership

Abstract Background: For transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM), the only category 1 regimens recommended by the National Comprehensive Cancer Network (NCCN) are lenalidomide and dexamethasone (Rd)-based, including triplet therapy with lenalidomide, bortezomib, and dexamethasone (RVd) (NCCN Myeloma v4.2018). Other doublet regimens, such as bortezomib and dexamethasone (Vd), are still a first-line option for patients with NDMM, especially for those who are elderly and/or frail. However, the latter population is either excluded or markedly underrepresented in clinical trials. Using an electronic health records (EHRs) database, we compared outcomes when either RVd or Vd were used in the treatment of transplant-ineligible patients with NDMM in a real-world practice setting, after adjusting for baseline demographic and clinical differences between the two cohorts. Methods: A retrospective observational study of patients with NDMM was conducted using EHRs from a nationally representative database (Flatiron Health). The Flatiron Network database is an enhanced oncology EHR database of patients treated at 265 clinics throughout the USA. Patients diagnosed with multiple myeloma, ICD-9 (203.0x) or ICD-10 (C90.xx), between January 2011 and May 2018 who were treated with RVd or Vd and did not undergo stem cell transplantation were included in the analysis. The primary comparison was time to next therapy (TTNT) in the overall population and in a subset of frail patients, as determined by a composite score based on age, Eastern Cooperative Oncology Group performance status (ECOG PS) score, and Charlson Comorbidity Index (CCI). Data regarding overall and progression-free survival (PFS) were limited as patient data prior to adoption of the Flatiron Network database were incomplete. Treatment-free interval (TFI) for patients who initiated a second-line therapy was defined as time from start of first-line to start of second-line therapy minus the duration of therapy (DOT). The Kaplan-Meier and Cox proportional hazard methods were used to calculate TTNT after adjusting for differences in patient baseline demographic and clinical characteristics. Results: Of the 8,470 transplant-ineligible patients with NDMM in the database, 2,369 were treated with either RVd (n = 1,309) or Vd (n = 1,060) and met the criteria for inclusion in this analysis. Patients treated with Vd were more likely to be older (median age 75 vs 70 years; P < 0.0001), frail (76.3% vs 65.4%; P = 0.0002), have creatinine clearance < 30 mL/min (23.9% vs 10.7%, P < 0.0001), have a higher ECOG PS score (P = 0.0031), and have International Staging System stage III disease (45.1% vs 28.8%; P < 0.0001). There were no significant differences in baseline neutropenia, anemia, or thrombocytopenia, or in median CCI. The proportion of patients with high-risk cytogenetics was lower in the Vd group (19.7% vs 26.0%; P < 0.0001). The mean DOT was longer for RVd (11.4 ± standard deviation [SD] 13.3 months) than for Vd (7.7 ± SD 9.7 months). However, the median adjusted TTNT was significantly longer with RVd than Vd (40.9 vs 14.8 months; hazard ratio [HR] 0.43; 95% confidence interval [CI] 0.33-0.55; P < 0.0001). The proportion of patients initiating a new treatment was lower in the RVd group (24.8% vs 40.6%; P < 0.0001). Among those who initiated a second-line therapy, the mean TFI for RVd compared with Vd was 42.6 versus 39.3 days, respectively (P = 0.2214). Among the 735 frail patients (416 RVd and 319 Vd), the median TTNT was significantly longer with RVd (32.6 vs 17.1 months; HR 0.40; 95% CI 0.29-0.54; P < 0.0001; Figure). Similar to the overall population, there were no significant differences in TFI (54.9 vs 29.6 days, P = 0.2598) and a significantly higher proportion of Vd patients initiated a new treatment (22.1% vs 36.4%; P < 0.001). Conclusions: In this real-world practice setting where PFS cannot be measured directly, triplet therapy with RVd significantly prolonged TTNT compared with Vd by 26.1 months in the overall patient population, and by 15.5 months in frail transplant-ineligible patients with NDMM. Disclosures Chari: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Research Funding; Amgen: Consultancy, 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, Research Funding; 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; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; The Binding Site: Consultancy; Array Biopharma: Research Funding; Bristol Myers Squibb: Consultancy. Ung:Celgene Corporation: Employment, Equity Ownership. Tian:Celgene Corporation: Employment. Agarwal:Celgene Corporation: Employment, Equity Ownership. Parikh:Celgene Corporation: Employment, Equity Ownership.

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Use of Alkylating Agents Among Patients with Multiple Myeloma in a National Registry, 2006-2008.

Blood ◽

10.1182/blood.v114.22.4941.4941 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4941-4941

Author(s):

Carla M Van Bennekom ◽

Theresa E Anderson ◽

Noopur Raje ◽

Kenneth C Anderson ◽

David W Kaufman

Keyword(s):

Multiple Myeloma ◽

Median Duration ◽

Research Funding ◽

Alkylating Agents ◽

Initial Therapy ◽

Novel Agents ◽

Second Line ◽

Second Line Therapy ◽

Line Therapy

Abstract Abstract 4941 Background While alkylating agents were among the earliest treatments for multiple myeloma, newer therapies have been available for several years. Here we describe patterns of use and effectiveness of alkylators in the modern landscape of myeloma treatment, based on a nationwide registry of recently diagnosed patients. Methods The “Patient Registries at Slone: Myeloma” is a national disease-based observational registry conducted by Boston University. All patients with myeloma diagnosed within 4 months of enrollment were eligible for inclusion. Subjects enrolled by mail or over the internet; information on treatment, clinical events, and quality of life was obtained by questionnaire and from medical record review at baseline and at six-month intervals. There were 342 patients with multiple myeloma residing in 43 states who were enrolled from June 2006-October 2008 and completed at least a baseline questionnaire. The median length of follow-up was 8 months after diagnosis (range 0.5-24). Results Alkylators were used as initial treatment in 26 patients (8%), as second-line treatment in 14 (4%), and as part of a transplant regimen in 76 (22%). Patients who received alkylators as initial or second-line therapy tended to be older (median age, 69 vs. 60 years, p<0.0005), and the combined prevalence of use was 17% among patients who did not have prescription drug insurance, compared with 11% among those who did (p=0.36). The prevalence of first-line use was 12% among patients diagnosed in 2006, 9% in 2007, and 4% in 2008 (p=0.09). Further results are confined to 34 of the 40 first or second-line alkylator recipients for whom medical records were available. The regimens used are shown in the table; the majority of patients received regimens that included melphalan. The median duration of initial therapy was 3 months (range 0.5-15); 6 patients (24%) had at least a partial response. Ten patients were still on treatment at the end of follow-up; in 15 (60%), alkylator therapy was changed to another regimen (11) or stopped without new therapy during the follow-up period (4), including 3 due to insufficient response and 5 due to toxicity. The new regimens were thalidomide-based in 2 patients, bortezomib-based in 3, bortezomib+lenalidomide in 1, dexamethasone without novel agents in 2, and 3 patients went directly to autologous stem-cell transplant. Second-line therapy with alkylators was initiated due to insufficient response from the previous regimen in 2 patients, because of side effects in 5, and for cost reasons in 2. The median duration was 2 months (range 0.5-12, with 4 patients still on treatment), and 4 (44%) had a partial or better response. The immediately preceding regimen was thalidomide-based in 5 patients, lenalidomide-based in 1, and bortezomib-based in 3; the median number of previous regimens was 2 per patient (range, 1-4). The median duration of previous therapy was 4 months (range 0.5-9). Conclusions The present population-based results indicate that in the modern era of myeloma treatment, the most prevalent use of alkylating agents is as conditioning for stem cell transplants; the drugs are also still used for initial treatment, mostly in combination with novel agents, although the prevalence was low overall and continued to decline during 2006-2008. Patients who received alkylators for initial or second-line therapy were older and the agents appeared to be somewhat more commonly used among those who did not have prescription drug insurance. The data suggest that there continues to be a useful role for alkylating agents as initial therapy, particularly for myeloma patients who are not transplant candidates, and occasionally as an early replacement for novel agents that prove ineffective or excessively toxic in individual patients. With a relatively short duration of follow-up, there was little information on the use of alkylators in the relapsed setting, where their high level of anti-myeloma activity might be expected to lead to more use. Disclosures Van Bennekom: Cephalon: Research Funding; Celgene: Research Funding; Millennium: Research Funding; Genentech: Research Funding. Anderson:Cephalon: Research Funding; Celgene: Research Funding; Millennium: Research Funding; Genentech: Research Funding. Raje:Celgene: Research Funding; Novartis: Research Funding; AstraZeneca: Research Funding. Anderson:Celgene: Consultancy, Research Funding, Speakers Bureau; Millennium: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau. Kaufman:Cephalon: Research Funding; Celgene: Research Funding; Millennium: Research Funding; Genentech: Research Funding.

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Second-Line Therapy for Immune Thrombocytopenia: Real-World Experience

Blood ◽

10.1182/blood-2019-128336 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2120-2120

Author(s):

Hasmik Nazaryan ◽

Yang Liu ◽

Emily Sirotich ◽

Joanne M Duncan ◽

Donald M. Arnold

Keyword(s):

Real World ◽

Research Funding ◽

Immune Thrombocytopenia ◽

Line Treatment ◽

Second Line ◽

Second Line Therapy ◽

Start Date ◽

Line Therapy ◽

Treatment Start

Background: Immune Thrombocytopenia (ITP) is an autoimmune platelet disorder that can lead to serious morbidity caused by bleeding and therapy-associated toxicities. The sequence of first-line therapies is well-defined, but the sequence of second-line therapies lacks consensus. A description of real-world experience is necessary to understand practice patterns with respect to second-line therapies and identify gaps in care. The objective of this study was to describe the types and chronological sequences of second-line therapies in a large cohort of ITP patients. Methods: This was a retrospective cohort study. The population was derived from the McMaster ITP Registry, a prospective longitudinal registry of patients presenting with thrombocytopenia (platelets <150 × 109/L) to an academic hematology clinic in Hamilton, Canada. Inclusion criteria were: 1) diagnosis of primary or secondary ITP at most recent follow-up; 2) received one or more second-line therapy since initial ITP diagnosis; and 3) ≥6 months of follow up. No exclusions were applied. The sequence of second-line therapies was determined by treatment start dates. For treatments that were administered before enrollment in the registry, the order of treatment was determined by the reported treatment start date. When the start date was not reported, the sequence of treatments was assumed to be the order in which they were mentioned in the medical records. Second-line therapies included: splenectomy; rituximab; danazol; dapsone; thrombopoietin receptor agonists (TPO-RAs): eltrombopag or romiplostim; and immunosuppressants: mycophenolate, cyclosporine, azathioprine or cyclophosphamide. Results: From January 2010 to December 2017, 789 patients with thrombocytopenia were registered in the McMaster ITP Registry. Of those, 204 had ITP and received second-line therapy (57.4% female). Median duration of ITP from the initial presentation to the most recent diagnosis was 9 years (IQR, 4-19). The proportion of patients who received each type of second-line therapy at any time were immunosuppressants (n=106, 52.0%), splenectomy (n=106, 52.0%), TPO-RAs (n=75, 36.8%), danazol (n=73, 35.8%), rituximab (n=67, 32.8%), and dapsone (n=4, 2.0%). Overall, 69 unique treatment sequences were identified. For patients who received one second-line treatment only (n=88), the most common single treatment was splenectomy (n=28, 31.8%), followed by immunosuppressants (n=21, 23.9%) and danazol (n=18, 20.5%) (Figure 1). For patients who received more than one second-line therapy (n=116), the most common treatment sequences were splenectomy followed by immunosuppressants (n=7, 6.0%); immunosuppressants followed by rituximab (n=6, 5.0%), and immunosuppressants followed by danazol (n=5, 4.0%). In patients who received each of these therapies, the last second-line treatments received were TPO-RAs (52/75, 69.3%), immunosuppressants (45/106, 42.5%), rituximab (37/67, 55.2%), splenectomy (36/106, 33.9%), danazol (33/73, 45.2%), and dapsone (1/4, 25%). Conclusion: The types and sequences of second-line therapies for ITP were variable in a large Canadian academic center, where access to certain treatments including TPO-RAs and rituximab is limited. In this setting, splenectomy and immunosuppressant medications were commonly used as early second-line therapies. TPO-RAs were most often the last second-line treatment in the sequence of therapies used. Drug accessibility and other factors related to the choice of second-line therapies require further evaluation. Disclosures Arnold: Bristol-Myers Squibb: Research Funding; Principia: Consultancy; Rigel: Consultancy, Research Funding; Novartis: Honoraria, Research Funding.

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Inferior Survival with Use of Autologous Stem Cell Transplant As Second-Line Therapy in Multiple Myeloma

Blood ◽

10.1182/blood-2019-127710 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2026-2026 ◽

Cited By ~ 1

Author(s):

Cara A. Rosenbaum ◽

Danny Luan ◽

Paul J Christos ◽

Roger Pearse ◽

Danielle Guarneri ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Research Funding ◽

Cell Transplant ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Line Therapy ◽

Delayed Group

Background: Multiple myeloma (MM) remains incurable with eventual relapse and death occurring despite multiple lines of chemotherapy. Standard frontline therapy for MM has traditionally consisted of combinations of immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and dexamethasone followed by consolidation with high-dose melphalan and autologous stem cell transplantation (ASCT). A randomized trial using IMiD and PI-based induction demonstrated significant progression-free survival (PFS) benefit with upfront ASCT in consolidation compared to ASCT in second-line at relapse, but no OS benefit (Attal et al, NEJM, 2017). Delay of ASCT to second-line or beyond may in part be due to the aforementioned lack of OS benefit shown with upfront ASCT and increase of sustained deep responses, including MRD negativity, to novel frontline 3 and 4-drug regimens and continuation of therapy in the frontline. We performed a chart review comparing PFS1, PFS2, and overall survival (OS) of patients who underwent upfront ASCT as consolidation to those who received ASCT in the second-line after one relapse ('delayed ASCT'). The study was approved by the Institutional Review Board at Weill Cornell Medical College. Methods: 124 MM patients who underwent ASCT either as consolidation in first-line or delayed ASCT after relapsing on one prior treatment between 2010-2016 were included. Demographics and clinical parameters were extracted from the electronic medical record. PFS1, PFS2, and OS were calculated from date of diagnosis to first relapse, second relapse, and death, respectively. Patients were censored if lost to follow-up prior to experiencing the relevant event. PFS1, PFS2, and OS of patients receiving upfront ASCT were compared to those of patients receiving delayed ASCT. Log-rank tests were used to statistically evaluate differences between Kaplan-Meier PFS/OS curves. Cox proportional hazards models were used to calculate hazard ratios (HR) using upfront ASCT as the reference treatment. Results: Among the 124 patients, 93 underwent upfront ASCT as consolidation and 31 underwent delayed ASCT after relapsing on one prior line of therapy (Table 1). Induction regimens and pre-transplant therapies received are detailed in Table 1. Of the delayed group patients, 6 underwent ASCT directly without second-line induction and 25 as consolidation after second-line therapy. Patients receiving upfront ASCT had significantly longer median PFS1 compared to patients who received delayed ASCT (6.45 vs 1.25 years; P<0.001), with a HR of 0.18 (95% CI, 0.11-0.29) (Figure 1A). Median PFS2 in the upfront ASCT group was likewise significantly longer than in the delayed group (9.19 vs 3.69 years; P<0.001), with a HR of 0.31 (95% CI, 0.18-0.55) (Figure 1B). With a median follow-up of 6.0 and 5.8 years in the upfront and delayed groups, respectively, median OS was not reached in either group but trended towards prolonged survival with upfront ASCT (P=0.052), with a HR of 0.46 (95% CI, 0.20 to 1.03) (Figure 1C). Conclusions: In this cohort of 124 MM patients undergoing ASCT as consolidation in the upfront setting or delayed ASCT in second-line after relapse, upfront ASCT was associated with significantly improved PFS1 and PFS2, similar to findings by Attal et al. However, in that study, no difference in OS was seen between upfront and delayed groups, while our data, with longer follow-up, showed median OS trending towards significance. This has important implications as with use of novel induction regimens and maintenance therapy, ASCT is more commonly being delayed to early relapse in second-line or beyond. If transplant is intended to be used in the first few lines of therapy, our data show that delaying ASCT even to second-line has a significant negative impact on PFS. In addition, a shorter OS with delayed transplant was suggested although did not reach statistical significance, possibly due to small numbers or more patients with high-risk MM in the delayed group. It is also important to note the lack of daratumumab-based regimens which may have improved PFS/OS in either or both arms. Thus, our findings should be prospectively validated in a larger trial of ASCT as consolidation in first-line vs second-line or beyond using novel, monoclonal antibody-based regimens. Disclosures Rosenbaum: Janssen: Research Funding; Honoraria Akcea: Other: Accordant Health. Coleman:Gilead, Bayer, Celgene: Consultancy, Research Funding, Speakers Bureau; Kite Pharmaceuticals: Equity Ownership; Merck: Research Funding; Pharmacyclics: Speakers Bureau. Van Besien:Miltenyi Biotec: Research Funding. Niesvizky:Takeda, Amgen, BMS, Janssen, Celgene: Consultancy, Research Funding.

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Efficacy and Safety of Ruxolitinib in the Treatment of Elderly Patients with Policythemia Vera Resistant/Intolerant to Hydroxyurea

Blood ◽

10.1182/blood-2021-149612 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2581-2581

Author(s):

Roberto Latagliata ◽

Daniela Bartoletti ◽

Alessandro Andriani ◽

Massimo Breccia ◽

Elena Rossi ◽

...

Keyword(s):

Board Of Directors ◽

Real World ◽

Age Groups ◽

Second Line ◽

Efficacy And Safety ◽

Second Line Therapy ◽

Advisory Committees ◽

Line Therapy ◽

Dose Reductions

Abstract Introduction: Ruxolitinib (Rux) has been recently approved as second-line therapy in patients (pts) with Polycythemia Vera (PV) resistant/intolerant to hydroxyurea (HU). Median age of PV pts enrolled in the pivotal Response trials was around 60 yrs; at present, no data is reported on the use of Rux in elderly pts. Aims: In a real-world cohort of PV pts treated with Rux, we investigated whether the efficacy and safety of Rux were comparable in pts who initiated therapy when aged ≥75 years compared with younger pts. Methods: After IRB approval, clinical/laboratory data of 934 WHO2016-defined PV pts followed in 29 Hematology Centers were retrospectively collected. Of them, 168 (17.9%) were considered resistant/intolerant to HU at any time during follow-up by responsible physician and shifted to Rux as second-line therapy. Results: Among the 168 pts treated with Rux, 42 (25%, median age 78.2 years) were aged ≥75 yrs at Rux start, 74 (44%, median age 67.7) were aged 60-74 and 52 (31%, median age 53) were <60 at Rux start. No significant differences were observed between the 3 groups, apart from a lower need for phlebotomies in pts aged ≥75 yrs and lower presence of palpable spleen in older pts (age ≥60), that more frequently switched to Rux due to HU intolerance (Table 1). Median duration of HU treatment was 41.0 months (IQR 14.6 - 85.8), with a trend for a longer median treatment duration in pts aged ≥75 [61.0 months (IQR 21.5 - 89.6) vs 35.9 months (IQR 13.4 - 79.6), p=0.04]. Rux starting dose was similar across age groups; however, more elderly pts underwent Rux dose reductions during follow-up (45.2% in pts aged ≥75 vs 28.6% in younger pts, p=0.04). Responses during Rux therapy are reported in Table 2, with no significant differences between the 3 groups at any time. In the overall cohort, response on PV-related symptoms at 6 and 12 months was significantly higher in pts who switched to Rux because of HU intolerance; however, this difference was not observed in pts aged ≥75 yrs. As to the most common hematologic Rux-related toxicities, grade 3-4 anemia and thrombocytopenia were observed in only 2 (1.2%) and 5 (3%) pts, with no difference across age groups (p=0.45 and p=0.18). However, any grade anemia and thrombocytopenia during Rux were more frequently observed in pts aged ≥75 (68.3% vs 51.7% of anemia, p=0.06 and 12.2% vs 3.5% of thrombocytopenia in younger pts, p=0.04). Nineteen and 4 pts experienced infectious and thrombotic complications during Rux with incidence rates of 0.59 and 0.12 per 100 patient-months, respectively, comparably in younger and older (≥75) pts (p=0.75 and p=0.29, respectively). Notably, 6 infections were herpes simplex/zoster virus, comparably distributed between the 3 groups (p=0.60). Permanent Rux discontinuation was needed in 14 pts (8.3%) after a median Rux exposure of 7.8 months (IQR 4.6 - 17.6) (incidence: 0.41 per 100 pts/months). Discontinuation was comparable between age groups, with Rux stop in 4 pts aged ≥75 yrs and 10 younger pts (2.4% vs 5.2% at 8 months, log-rank p=0.75). At last follow-up, 2 pts had died (1 from 2 nd neoplasia after 19.1 months from Rux start and 1 from acute leukemia after 3.3 years), both pts aged 60-74 yrs. Conclusions. In this real-world analysis, use of Rux in HU resistant/intolerant elderly PV pts was effective and safe despite the more frequent need for dose reductions. Older age should not discourage Rux therapy, but stricter hematological monitoring may be suggested. Figure 1 Figure 1. Disclosures Latagliata: BMS Cellgene: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Breccia: Pfizer: Honoraria; Incyte: Honoraria; Bristol Myers Squibb/Celgene: Honoraria; Abbvie: Honoraria; Novartis: Honoraria. Bonifacio: Amgen: Honoraria; Bristol Myers Squibb: Honoraria; Novartis: Honoraria; Pfizer: Honoraria. Cavo: Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria; 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; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria; 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, EXPENSES, Speakers Bureau; Bristol-Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Palandri: AOP: Membership on an entity's Board of Directors or advisory committees; Sierra Oncology: Membership on an entity's Board of Directors or advisory committees; CTI: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

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Second Line Therapy with Second Generation TKI After Intolerance to Imatinib Based Treatments Showed High Overall Survival in Contrast to Second Line Therapy After Resistance; Results of the Randomized CML Study IV

Blood ◽

10.1182/blood.v118.21.781.781 ◽

2011 ◽

Vol 118 (21) ◽

pp. 781-781

Author(s):

Susanne Saussele ◽

Michael Lauseker ◽

Ulrike Proetel ◽

Martin C. Müller ◽

Benjamin Hanfstein ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Second Generation ◽

Chronic Phase ◽

Imatinib Therapy ◽

Second Line ◽

Second Line Therapy ◽

Advisory Committees ◽

Line Therapy

Abstract Abstract 781FN2 Introduction: Data on second line therapy with second generation tyrosine kinase inhibitors (TKI) in CML treatment were generated mainly from phase II/III industry initiated trials (Review Hehlmann Exp Op. 2011). 24-month overall survival (OS) varies between 88% and 94% after intolerance and/or resistance to imatinib for chronic phase (CP) and between 67% and 72% for accelerated phase (AP) or blast crisis (BC). Intention to treat analyses including outcome of patients after discontinuation of first line therapies have not been available as yet. We thought to evaluate overall and progression-free survival (OS and PFS) of imatinib intolerant vs. resistant patients under second line TKI with long-term follow-up within an investigator initiated trial. Methods: We analyzed data of the German CML study IV, a randomized 5-arm trial to optimize imatinib therapy on an intention to treat basis. According to protocol, follow-up of patients on and after second generation TKI after imatinib intolerance and/or resistance was continued for OS and PFS. Analysis of PFS was only relevant, if intolerance and resistance to imatinib therapy occurred while a patient was still in chronic phase (CP). Patients were censored at the time of allogeneic stem cell transplantation (allo-SCT). Results: From July 2002 to December 2010, 1,502 patients with Philadelphia chromosome and /or BCR-ABL positive CML in CP were randomized. 129 patients of the “imatinib after interferon arm” and 36 other patients had to be excluded (14 due to incorrect randomization or withdrawal of consent, 22 with missing baseline information). 1337 were randomized to primary imatinib treatment (imatinib 400 mg vs. imatinib 800 mg vs. imatinib in combination with either interferon alpha or araC). Of these, 234 (17%) discontinued imatinib therapy. 156 patients were treated with 2nd generation TKI, 61 were directly referred to allo-SCT, 17 patients received other regimens (including interferon alpha only or hydroxyurea). 120 of 156 patients started second generation TKI therapy (nilotinib, n=41, dasatinib, n=75, bosutinib, n=2, nilotinib and dasatinib, n=2) within 3 months after stopping imatinib, received treatment for at least one week and were evaluable for PFS and OS. 36 patients received second TKI later (median 10 months, range 3.5–61.4). Median age was 50 years (range 16–78), 42.5% were female. 48 patients were intolerant, 48 failed imatinib within CP and 24 after loss of CP (accelerated phase, n=10, blast crisis, n=14). Median time to second generation TKI was 17 months (range 1.4–97 months) and median follow-up after start of second-line TKI 31 months (range 0.2–71 months). Risk stratification according to the EUTOS Score was high in 20 patients (17%) and low in 94 patients (78%) and unknown in 6 patients (5%). OS for all 120 patients 3 years after start of second generation TKI was 73%, 96% for intolerant and 80% for resistant patients in CP and 19% for resistant patients in advanced disease (s. Fig. 1). According to EUTOS score, 3-year OS was 78% for low and 56% for high risk patients. Probability of PFS of the 96 patients in 1st CP after 3 years was 96% for intolerant and 76% for resistant patients. After 2nd generation TKI, 18 patients received an allo-SCT: all were in CP, 2 patients after imatinib intolerance, 16 patients after imatinib resistance. Conclusion: Survival on second generation TKI is high for imatinib intolerant patients in first CP but much lower for resistant patients in first CP or for patients with advanced disease phases. Alternative treatment strategies are warranted for these patient groups. Disclosures: Krause: Micromet: Research Funding. Kneba:Hoffmann La Roche: Honoraria. Hochhaus:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Ariad: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. German CML Study Group:Deutsche Krebshilfe: Research Funding; Novartis: Research Funding; BMBF: Research Funding; EU: Research Funding; Roche: Research Funding; Essex: Research Funding.

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Efficacy Of Dasatinib Therapy In Patients With Imatinib-Resistant Or -Intolerant Chronic Myeloid Leukemia From Physician’s and Patient’s Perspective: “Real World” Data

Blood ◽

10.1182/blood.v122.21.5185.5185 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5185-5185

Author(s):

Tatyana I Ionova ◽

Tatyana P Nikitina ◽

Taras A Gritsenko ◽

Valentina L Ivanova ◽

Galina B Kuchma ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Real World ◽

Myeloid Leukemia ◽

Research Funding ◽

Base Line ◽

Second Line ◽

Second Line Therapy ◽

Line Therapy ◽

Patient Reported ◽

Dasatinib Treatment

Abstract There is limited published data about the efficacy and safety of the second-line therapy with dasatinib in patients in chronic phase chronic myeloid leukemia (CML-CP) in a “real world” patients setting outside clinical trials. In addition, comprehensive evaluation of benefits and risks of the treatment is worthwhile to better define treatment outcomes in this patients’ population. We aimed to study clinical and patient-reported outcomes as well as safety of dasatinib treatment in a “real world” setting within the context of its approved indication through the analysis of prospectively collected data in patients with imatinib resistance or intolerance receiving dasatinib as the second-line therapy. 75 CML-CP patients resistant or -intolerant to imatinib were enrolled in the prospective, multicenter, non-interventional study (mean age 51.3 years old, SD 15.4; range 22–83 years; male/female – 37/38). The median of disease duration was 5.0 years (0.75–17 years). 63 patients had resistance to imatinib; 12 patients were intolerant to imatinib; the median duration of imatinib treatment 40 months (3–121 months). All the patients received dasatinib as the second-line therapy (100 mg daily). Median follow-up was 12 months. For quality of life (QoL) and symptom assessment patients filled out the SF-36 and Comprehensive Symptom Profile in Chronic Myeloid Leukemia Patients (CSP Leuk-CML), respectively, at base-line, in 1, 3, 6 months after treatment start and every 6 months thereafter. Comparison of QoL and symptom scores was conducted using t-test. QoL scores were analyzed using t-test, adjusting for sociodemographic and disease status. Mean symptom severity and percentage of patients with moderate-to-severe (ratings ³ 5) symptoms was evaluated. After 12 months of treatment 83% patients achieved or maintained complete hematologic response and 35 % – complete cytogenetic response. The twenty four-month progression free survival rate was 93% (95% CI; 84–97%). Four cases of pleural effusion events were registered: they were easily managed in 3 cases; one patient died at 1 month after treatment start due to accompanied infection complication. No severe hematological adverse effects were observed except two cases of grade III-IV neutropenia. Two patients were resistant to dasatinib. Two patients died of disease progression at 6 months of follow-up. At 12 months of dasatinib treatment QoL parameters were stable for 5 out of 8 scales; vitality, social functioning and mental health significantly improved as compared with base-line (p< 0.01). At 24 months of dasatinib treatment improvement of physical functioning, vitality, social functioning and mental health as compared with base-line was registered (p< 0.01); no worsening was observed for other QoL scales. Before treatment 75% of patients experienced at least one moderate-to-severe symptom; more than 40% had more than 7 moderate-to-severe symptoms. The majority of patients (96%) experienced fatigue; half of them suffered from moderate-to-severe fatigue. While treatment the number of patients with moderate-to-severe symptoms decreased. After 12 months of therapy only 25% of patients experienced moderate-to-severe fatigue. Before treatment 36% of patients exhibited critical or severe QoL impairment. Remarkably, in the subgroup of patients (44%) with critical or severe QoL impairment at base-line dramatic QoL improvement was observed: QoL index increased 3.4 fold (p<0.01). Thus, our study on “real world” patient data confirms that dasatinib as second-line therapy in CML-CP patients is effective both in terms of clinical outcomes and patient-reported outcomes, as well as exhibits good tolerability. Comprehensive evaluation of the outcomes of the second-line treatment of CML-CP allows to assess the benefits and risks of therapy both from physician’s and patient’s perspective. Disclosures: Ionova: BMS: Research Funding. Nikitina:BMS: Research Funding. Gritsenko:BMS: Research Funding. Ivanova:BMS: Research Funding. Kuchma:BMS: Research Funding. Shnaider:BMS: Research Funding. Sannikova:BMS: Research Funding. Fedorenko:BMS: Research Funding. Kurbatova:BMS: Research Funding.

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Comparison of Survival Rates, Healthcare Resource Use and Costs of Elderly Patients with Chronic Myeloid Leukemia Receiving Dasatinib or Nilotinib As Second-Line Therapy

Blood ◽

10.1182/blood.v124.21.2618.2618 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2618-2618

Author(s):

B. Douglas Smith ◽

Jun Liu ◽

Dominick Latremouille-Viau ◽

Zhou Zhou ◽

Annie Guerin ◽

...

Keyword(s):

Research Funding ◽

Index Date ◽

Survival Rates ◽

Baseline Period ◽

Harvard University ◽

Second Line ◽

Second Line Therapy ◽

Analysis Group ◽

Line Therapy

Abstract Introduction: Dasatinib and nilotinib are two second-generation tyrosine kinase inhibitors (TKIs) that are well established as treatment options for patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase resistant or intolerant to imatinib and the treatment guidelines do not differentiate based on patient age. Importantly, elderly patients (≥65 years old) account for about half of CML patients; yet there are little data reported focusing on outcomes in this distinct group of patients, often with multiple medical problems and different socio-economic profiles when compared to younger patients. This study aimed to compare survival rates, healthcare resource utilization (HRU), and medical service costs between elderly CML patients receiving dasatinib versus nilotinib as second-line therapy after imatinib. Methods: Patients aged ≥65 years with ≥2 CML diagnoses who received imatinib as first-line therapy followed by nilotinib or dasatinib as second-line therapy were identified using the Medicare Research Identifiable Files (RIF) from 2006 to 2012. Selected patients were continuously enrolled in the Part A (i.e., institutional claims), Part B (i.e., non-institutional claims), and Part D (i.e., drug events) for ≥6 months before and ≥1 month after the second-line TKI therapy initiation date (i.e., index date). Patients enrolled in a clinical trial, those with a stem-cell transplant, or receiving chemotherapy (except hydroxyurea) during the 6 months before the index date (i.e., baseline period) were excluded from the study. Based on the second-line TKI, patients were classified as nilotinib users or dasatinib users. Survival rates were estimated using Kaplan Meir analyses and compared between nilotinib and dasatinib users using Cox proportional-hazards models. HRU and healthcare costs (USD 2013; payer’s perspective) were observed from the index date up to the end of follow-up. Because the length of follow-up varied across patients, HRU and costs were reported per-patient-per-month (PPPM). Incidence rate ratios (IRR) were estimated using Poisson regression models and monthly cost differences were estimated using general linear models with a log link and a gamma distribution or two-part models. Multivariate regression analyses were used to adjust for potential confounding factors measured during the baseline period or at the index date. Results: After applying the sample selection criteria, 659 patients using a second-line TKI therapy were selected; 280 were nilotinib users and 379 were dasatinib users. On average, patients had a follow-up of 24 months (median=22 months) after the index date. The mean age was 76 years and most patients were female (62%). Nilotinib and dasatinib users were generally similar in terms of gender, region of residence, prior imatinib treatment duration, CML complexity, and comorbidity profile. However, nilotinib users were slightly older than dasatinib users; a greater proportion of nilotinib users were 80+ years old at the index date (35% of nilotinib users vs. 27% of dasatinib users; p=.039). In addition, the proportion of patients with cardiovascular disease (40% of nilotinib users vs. 31% of dasatinib users; p=0.015) or congestive heart failure (23% of nilotinib users vs. 14% of dasatinib users; p=0.002) during the baseline period was higher in nilotinib users when compared to dasatinib users. Despite these differences, the median survival time was >4.9 years for nilotinib users and 4.0 years for dasatinib users (log rank test p=.032). After adjusting for potential confounding factors, nilotinib users had a mortality risk that was 38% lower than that of dasatinib users (p=.006) and, nilotinib users had 21% fewer inpatient admissions, 17% fewer inpatient days, 31% fewer emergency room visits, and 12% fewer outpatient visits when compared to dasatinib users (PPPM; all p≤.001). The adjusted monthly medical cost was $378 lower in nilotinib users when compared to dasatinib users (PPPM; p=.045). Conclusion: This retrospective study of elderly Medicare beneficiaries with CML receiving second-line therapy with dasatinib or nilotinib suggested that those receiving nilotinib had longer survival, lower HRU, and lower medical costs than those receiving dasatinib. Further health outcome researches and longer term studies focusing on elderly CML are needed to better define the best practice patterns. Disclosures Liu: Jun Liu is an employee of Harvard University which has received research funding from Analysis Group, Inc.: Employment. Latremouille-Viau:Dominick Latremouille-Viau is an employee of Analysis Group, Inc. which has received consulting fees from Novartis Pharmaceuticals Corporation: Employment. Zhou:Zhou Zhou is an employee of Analysis Group, Inc. which has received consulting fees from Novartis Pharmaceuticals Corporation: Employment. Guerin:Annie Guerin is an employee of Analysis Group, Inc. which has received consulting fees from Novartis Pharmaceuticals Corporation: Employment. Fernandez:Daniel Fernandez is an employee of Harvard University which has received research funding from Analysis Group, Inc.: Employment. Yi:Dingdong Yi is an employee of Harvard University which has received research funding from Analysis Group, Inc.: Employment. Wang:Xufei Wang is an employee of Harvard University which has received research funding from Analysis Group, Inc.: Employment. Wu:Eric Q. Wu is an employee of Analysis Group, Inc. which has received consulting fees from Novartis Pharmaceuticals Corporation: Employment. Mhatre:Novartis Pharmaceuticals Corporation: Employment. Keir:Novartis: Employment, Equity Ownership. Chen:Novartis: stock options Other; Novartis Pharmaceuticals Corporation: Employment.

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Real-World Treatment Patterns and Outcomes Among Patients with Hairy Cell Leukemia

Blood ◽

10.1182/blood.v126.23.2125.2125 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2125-2125

Author(s):

Sudeep Karve ◽

Victoria Divino ◽

Andrew Gaughan ◽

Mitch DeKoven ◽

Guozhi Gao ◽

...

Keyword(s):

Health Plan ◽

Real World ◽

Index Date ◽

Treatment Patterns ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy

Abstract Background and Objective : Hairy cell leukemia (HCL) is a rare condition and accounts for ~2% of all leukemia cases in the US. NCCN guidelines recommend first-line agents including pentostatin and cladribine among patients with HCL. However, a paucity of data exists with regard to real-world treatment patterns among patients with HCL. Current study evaluates treatment patterns and associated clinical outcomes among patients with HCL using a large US administrative claims database. Methods : This retrospective observational study was conducted using the IMS Health PharMetrics Plus Health Plan Claims Database (2006-2014), which includes over 150 million unique health plan members across the US and is nationally representative of the commercially-insured US population. Data includes date stamped medical and pharmacy records along with information on health plan enrollment. Individuals with at least 2 medical claims with a diagnosis for HCL (identified using ICD-9-CM cod: 202.4x) were selected and the first observed claim defined the "index date." Patients <18 years of age at index date or with other malignancies during 6 months (the "pre-index period") prior to index date were excluded. Patients were required at least 90 days of continuous enrollment (the variable "follow-up period") in the health plan post index date with exception of patients who died within 3 months of diagnosis. Patients were followed until death (recorded on inpatient discharge disposition), end of enrollment or end of database, whichever occurred earlier. Study measures including patient demographic and baseline clinical characteristics, line of therapy (LOT), treatment patterns, relapse (receipt of same or new regimen in subsequent LOT following a gap of 365 days) and refractory disease (receipt of same or new regimen where the gap of two adjacent LOTs was <365 days) and post-treatment complications were assessed during the follow-up period. All analyses were descriptive in nature. Results : The study cohort included 749 patients after applying the selection criteria (mean follow-up from diagnosis 32 months). At diagnosis, the mean age (standard deviation) of the study cohort was 56 (10) years and majority of patients were male (77%). Mean baseline comorbidity burden (assessed using Charlson Comorbidity Index score) was 0.8 (1.1) with hypertension (24%) and aplastic anemia (22%) being the two most common co-morbidities. Only 38% (n=282) of patients received first-line chemotherapy post diagnosis. Majority initiated first-line cladribine (76%) as a single agent, while 9% had evidence of single agent pentostatin. Mean time to initiation of first-line therapy from diagnosis was 132 (294) days and average time on first-line therapy was 34 (104) days. Among patients with first-line therapy 14% received second-line therapy and rituximab (53%) and cladribine (21%) were frequently observed second-line agents. Post first-line therapy, mean time to initiation of second-line therapy was 303 (406) days. Among second-line initiators, 76% had refractory disease and 24% had relapsed following first-line. Neutropenia and fever were frequently reported complications while on chemotherapy. Conclusion : The real-world chemotherapy utilization patterns observed in this study are consistent with the NCCN guidelines with cladribine and pentostatin being the agents of choice for first-line therapy. Following diagnosis, more than one-third of patients initiated chemotherapy and only a small proportion of these received second-line chemotherapy suggesting durable response with first-line therapy. Limited follow-up post first-line therapy may have impacted the proportion of patients initiating second-line therapy as well as categorization of refractory and relapse disease. Disclosures Karve: AstraZeneca: Employment. Divino:IMS Health: Employment, Other: IMS Health received funding from AstraZeneca for this study. Gaughan:AstraZeneca: Employment. DeKoven:IMS Health: Employment, Other: IMS Health received funding from AstraZeneca for this study. Gao:MedImmune: Employment. Lanasa:MedImmune: Employment.

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Natural History of Skeletal Related Events in Patients with Multiple Myeloma Who Received First- and Second- Line Therapy with Novel Agents: Results from a Single Center Analysis in 620 Patients

Blood ◽

10.1182/blood-2019-123606 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4326-4326

Author(s):

Evangelos Terpos ◽

Nikolaos Kanellias ◽

Eftathios Kastritis ◽

Maria Gavriatopoulou ◽

Vassilis Koutoulidis ◽

...

Keyword(s):

Research Funding ◽

Novel Agents ◽

Long Bone ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Skeletal Related Events ◽

First Relapse

Introduction: Skeletal-related events (SREs) that include pathological fractures, spinal cord compression (SCC) and need for radiotherapy or surgery to the bone are frequent complications of multiple myeloma (MM). Although the incidence of SREs at diagnosis is well-documented, there is limited information for the natural history of SREs during treatment with novel agents. Thus, we evaluated the SRE rate in MM patients who received frontline and second line therapy with proteasome inhibitors (PIs) or immunomodulatory drug (IMiD)-based therapies and explored possible correlations with disease or genetic features and type of treatment. Methods: MM patients who received frontline therapy in our center (Department of Clinical Therapeutics, University of Athens, Greece), between 2007-2017, were included in this analysis. Patients had a whole-body skeletal survey using either conventional radiography (WBXR) or low-dose CT (WBLDCT) at diagnosis and then at the time of relapse or whenever clinically indicated. Magnetic Resonance Imaging (MRI) of the spine and pelvis at diagnosis was recorded when available. SNPs in genes that are involved in bone destruction in osteoporosis were also evaluated: LRP5 (rs4988321), GC vitamin D (rs4588), TNFRSF11A (rs3018362), DKK1 (rs1569198), RANKL (rs9594759), OPG (rs6469804) and ERS1 (rs1038304). Results: In total, 620 consecutive patients with symptomatic MM (316M/304F, median age: 65 years) were studied. The median follow-up was 54 months. At diagnosis, osteolytic disease was present in 408 (66%) patients. MRI was available in 390 patients: 149 (38%) patients had focal, 139 (36%) diffuse, 81 (21%) normal and 21 (5%) variegated pattern of marrow involvement. SREs were observed in 271 (44%) patients at diagnosis: 213 (34%) presented with pathological fractures (183 with vertebral fractures, 18 with rib fractures and 15 with long bone fractures; 32 patients had both vertebral and long bone or rib fractures), while 34 (5.5%) patients needed surgery to bone, 45 (7.2%) radiotherapy and 31 (5%) patients presented with SCC. The incidence of SREs was higher in patients with osteolytic lesions (76.4% vs. 12.4%, p<0.0001) or abnormal MRI pattern (49% vs. 11.3%, p<0.0001) at diagnosis. No correlation was found between the presence of SREs at diagnosis and a specific SNP of those studied. Frontline therapy with IMiD-based regimens was given in 38% of patients; 27% patients received bortezomib-based regimens and 28% both IMiD and bortezomib-based therapies (VTD or VRD); 7% received only conventional chemo. Bisphosphonates (BPs) were given to 465 patients (75%) at diagnosis; the vast majority (91%) received zoledronic acid. The remaining 155 patients did not receive upfront BPs, mainly due to renal insufficiency. During first line treatment, 39 (6.3%) patients developed a SRE: 25/341 (7.3%) on bortezomib- (including combos with an IMiD) and 14/235 (6%) on IMiD-based regimens. At the time of first relapse, 4.5% of patients presented with new fractures and 12% required local radiotherapy to bone (SRE rate: 16.5%). The rate of SREs at first progression was much higher in patients who did not receive upfront BPs (92.3% vs. 7.7%). There was no difference in the incidence of SREs at first relapse between patients who received PI- vs. non-PI-based regimens as first line therapy (54.2% vs. 45.8%, p=0.544). During second line therapy, 12.2% of patients developed a SRE, with no difference regarding the second line therapy (PI- or IMiD-based regimens). In total, 126 (20.3%) patients developed at least one SRE, during the course of the first and second line of therapy; this was more common in those who presented with an SRE at diagnosis (33% vs 12%; p<0.03). Conclusions: Our data, which constitutes one of the few systematic reports on the incidence and characteristics of SREs in the era of novel agents, indicate that SREs remain a significant complication in MM. Despite high response rates after first line therapy and the broad use of BPs, more than 20% of patients develop a new SRE during the first and second line treatment or at the time of first relapse. Importantly, patients who do not receive BPs due to renal impairment develop very frequently SREs, suggesting an unmet need in this setting. More effective frontline therapies or more potent bone-targeted agents (denosumab or anti-sclerostin drugs) may manage to further reduce the SREs rate in MM patients, especially in those who cannot receive BPs. Disclosures Terpos: Celgene: Honoraria; Janssen: Honoraria, Other: Travel expenses, Research Funding; Amgen: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel expenses, Research Funding; Genesis: Honoraria, Other: Travel expenses, Research Funding; Medison: Honoraria. Kastritis:Pfizer: Honoraria; Prothena: Honoraria; Genesis: Honoraria; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria. Gavriatopoulou:Amgen: Honoraria; Takeda: Honoraria, Other: Travel expenses; Janssen: Honoraria, Other: Travel expenses; Genesis: Honoraria, Other: Travel expenses. Dimopoulos:Sanofi Oncology: Research Funding.

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