Clinically Suspected Cast Nephropathy: A Retrospective, Multi-Center, Real-World Study

INTRODUCTION Myeloma cast nephropathy (CN) is the most common form of monoclonal immunoglobulin-mediated kidney disease, resulting from the precipitation of excessive amounts of monoclonal serum free light chains (sFLC) and causing around 70% of the cases of dialysis-dependent renal failure in multiple myeloma (MM)(Heher et al. 2013; Nasr et al. 2012; Sanders et al. 1991). In patients with acute renal failure, the finding of a high sFLC concentration with an abnormal sFLC ratio raises the clinical suspicion of CN (Hutchison et al. 2011). Although the histopathologic diagnosis of CN is established by renal biopsy, in routine clinical practice, the diagnostic yield of this procedure is often outweighed by the urgent need of anti-myeloma treatment and the risk of procedure-related complications. Recruitment of patients with CN into clinical trials is challenging and therefore real-world data on clinically suspected CN are necessary to understand the clinical characteristics, treatment and prognosis of these patients (Bridoux et al. 2017; Hutchison et al. 2019). METHODS We searched the population-based Danish Multiple Myeloma Registry for patients diagnosed with MM according to the International Myeloma Working Group criteria between 1st of January 2013 and 31st of December 2017 with a serum creatinine concentration of 200 µg/L or higher and a sFLC concentration of 1000 mg/L or higher at diagnosis. We conducted a retrospective patient chart review in eight Danish centers and assessed baseline characteristics, biopsy results, and overall survival. Anti-myeloma treatment, sFLC levels and renal function were registered during the first 12 months after MM diagnosis. RESULTS We identified 181 patients (176 with accessible clinical records). The median age was 72 years, the median serum creatinine was 384 µg/L, the median involved sFLC concentration was 5960 mg/L and dialysis dependent renal failure was present in 35%. Pre-myeloma estimated glomerular filtration rate (eGFR) was available in 80%, the median eGFR was 66 ml/min/1.73 m2. A kidney biopsy was carried out in 21% of patients and showed CN in 70% of cases. The median time from first sFLC measurement to initiation of therapy was 4 days. The number of lines of therapy ranged between zero and six. 173 patients received one, 35 patients received two and 14 patients received three lines of therapy during the first 12 months from diagnosis. High-dose melphalan with autologous stem cell transplantation (HDT-ASCT) was carried out in 45 (26%) patients. Bortezomib was administered as part of the first-line regimen in 163 (94%) patients. The most common first-line regimens were bortezomib-dexamethasone (n=67) and cyclophosphamide-bortezomib-dexamethasone (n=46). The first line of therapy resulted in very good partial response or better in 50% (Figure 1A), but was discontinued due to death, toxicity or progressive disease in 38% of patients. Dialysis dependency, eGFR and involved sFLC concentration were assessed at the end of the first cycle, at three months, six months and 12 months after initiation of therapy. At all these time points, achievement of renal recovery was associated with the magnitude of reduction of involved sFLC (Figure 1B). The median overall survival was 3.3 years (Figure 1C). At 12 months after diagnosis, 68% of patients were alive and 15% were dialysis dependent. Reduction of the initial involved sFLC concentration to ≤ 10% at three months was strongly associated with longer OS in a multivariate cox regression analysis adjusted for age and HDT-ASCT; hazard ratio 0.42, p=0.003. CONCLUSION In conclusion, we assessed a population-based cohort of newly diagnosed MM patients presenting with a serum creatinine of 200 µg/L or higher together with a sFLC of 1000 mg/L or higher. Although CN could have been clinically suspected in these cases, a kidney biopsy was only performed in one fifth of the population. Bortezomib-based therapy was initiated quickly and resulted in deep responses in most patients. Approximately one third of patients died within a year from MM diagnosis. Achievement of early and deep reduction in involved sFLC resulted in longer OS. Figure 1 Disclosures Szabo: Janssen: Consultancy. Vangsted:Takeda: Membership on an entity's Board of Directors or advisory committees; Jansen: Honoraria; Celgene: Honoraria; Sanofi: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees. Plesner:Celgene: Consultancy; AbbVie: Consultancy; Genmab: Consultancy; Oncopeptides: Consultancy; Takeda: Consultancy; Janssen: Consultancy, Research Funding.

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Evolving Unmet Need in Patients Refractory to Lenalidomide: Overview of the Clinical Trials in Relapsed/Refractory Multiple Myeloma

Blood ◽

10.1182/blood-2020-142642 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 22-23

Author(s):

Maria-Victoria Mateos ◽

Rohan Medhekar ◽

Istvan Majer ◽

Mehmet Turgut

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Literature Review ◽

Board Of Directors ◽

Unmet Need ◽

Publicly Traded ◽

First Line ◽

Advisory Committees ◽

Line Of Therapy

Introduction: The majority of newly diagnosed multiple myeloma (NDMM) patients are currently treated with lenalidomide-based regimens as their first line of therapy. This trend is likely to continue in the coming years. Typically, lenalidomide is administered until disease progression and has significantly contributed to better outcomes in these patients. However, most patients relapse, and prognosis worsens with each relapse. The choice of optimal treatment for patients who relapse while receiving lenalidomide as first line of therapy is unclear. Moreau et al (Blood Cancer J. 9, 38 [2019]) concluded that there is limited data on approved combinations for treating these patients and are restricted by the low number of lenalidomide-refractory patients enrolled in the pivotal trials. Results from the ongoing clinical trials of the combination of carfilzomib and anti-CD38 antibodies were not available at the time of the Moreau et al publication. The aim of this targeted literature review was to include this new data and to summarize currently available evidence on progression-free survival (PFS) for the treatment of RRMM patients who progressed on lenalidomide-based regimens. Methods: A targeted literature review was conducted to identify registrational clinical trials in patients with RRMM reporting PFS outcomes. PubMed, congress proceedings, and product labels were searched between Jan 2014 to July 2020. In addition to PFS, demographic, disease characteristics and treatment history were extracted for the trial populations to contextualize potential variations in study outcomes. The regimens studied in these trials were classified as lenalidomide-based, proteasome inhibitor (PI)-based and pomalidomide-based. Number of prior lines of therapy, prior exposure and refractoriness to lenalidomide and bortezomib were reported. Results: Twelve registrational trials were identified based on the search criteria (Table 1). Most pivotal trials assessing lenalidomide-based regimens (POLLUX, ELOQUENT-II, TOURMALINE-MM1) except the ASPIRE trial excluded patients who were refractory to lenalidomide. Trials evaluating PI-based regimens (e.g., CANDOR) or pomalidomide-based regimens (e.g., OPTIMISMM) included these patients, with more recent studies enrolling a larger proportion. Percentage of lenalidomide-exposed (and lenalidomide refractory) ranged from 40% (32%) in CANDOR to 98% (90%) in ELOQUENT III. These studies also enrolled a larger proportion of patients who were bortezomib-exposed, although most of these patients were at first relapse, with the exception of ELOQUENT III and ICARIA where most patients were at third relapse. Among lenalidomide-refractory patients, the median-PFS (mPFS) observed for the pomalidomide-based regimens ranged from 9.5 to 10.1 months and that observed for PI-based regimens ranged from 4.9 to 25.7 months. PFS in the lenalidomide-refractory subgroup was considerably shorter than in the ITT population. The mPFS for patients receiving carfilzomib/daratumumab/dexamethasone (KDd; CANDOR) and isatuximab/carfilzomib/dexamethasone (IsaKd; IKEMA) was not reached at median follow-up of 16.9 and 20.7 months respectively. While the mPFS for (KDd) for lenalidomide-refractory patients in CANDOR trial was not yet reached at median follow up of 16.9 months; the mPFS of 25.7 months for KDd in the MMY-1001 trial appears to be the longest among the assessed regimens. Conclusion: Patients refractory to lenalidomide have shorter PFS and represent a population with high unmet need. This targeted literature review suggests that the PI-based KDd regimen provides longer PFS compared to other lenalidomide-sparing regimens in lenalidomide-refractory populations. Heterogeneity across trial populations may limit the comparability of these treatments. Disclosures Mateos: Regeneron: 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; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: 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; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Honoraria; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie/Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; PharmaMar-Zeltia: Consultancy; GlaxoSmithKline: Consultancy. Medhekar:Amgen Inc.: Current Employment, Current equity holder in publicly-traded company. Majer:Amgen (Europe) GmbH: Current Employment, Current equity holder in publicly-traded company.

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A Phase III Study to Determine the Efficacy and Safety of Lenalidomide in Combination with Melphalan and Prednisone (MPR) in Elderly Patients with Newly Diagnosed Multiple Myeloma.

Blood ◽

10.1182/blood.v114.22.613.613 ◽

2009 ◽

Vol 114 (22) ◽

pp. 613-613 ◽

Cited By ~ 17

Author(s):

Antonio Palumbo ◽

Meletios A. Dimopoulos ◽

Michel Delforge ◽

Martin Kropff ◽

Robin Foa ◽

...

Keyword(s):

Multiple Myeloma ◽

Maintenance Therapy ◽

Board Of Directors ◽

Primary Endpoint ◽

Interim Analysis ◽

Newly Diagnosed ◽

Efficacy And Safety ◽

Time To Progression ◽

First Line ◽

Advisory Committees

Abstract Abstract 613 Background: Lenalidomide (Revlimid®) is an oral immunomodulatory agent with clinical efficacy in patients with multiple myeloma (MM). In patients with relapsed/refractory MM, lenalidomide plus dexamethasone improved time to progression (TTP) and overall survival (OS) in comparison with dexamethasone alone. In newly diagnosed MM patients, the current study compares the efficacy and safety of melphalan, prednisone and lenalidomide (MPR) with that of MP alone. Methods: Key inclusion criteria were: ≥65 years of age, newly diagnosed and symptomatic MM. 459 patients were randomly assigned to receive MPR followed by lenalidomide maintenance therapy or MPR followed by placebo maintenance therapy or MP followed by placebo maintenance therapy (Figure 1). The study induction and maintenance phases were followed by an open label lenalidomide extension and a follow-up phase. All patients received aspirin 100 mg/day as thrombo-prophylaxis. The primary endpoint of the study is progression free survival (PFS). The secondary endpoints are OS, time-to-progression, response rate, time to response, response duration, time-to-next anti-myeloma therapy, safety, quality of life and exploratory assessment of cytogenetic abnormalities. Primary comparison is based on the intent-to-treat population comparing PFS between MPR followed by lenalidomide with MP followed by placebo; secondary comparisons are between MPR followed by lenalidomide and MPR followed by placebo, and between MPR followed by placebo and MP followed by placebo. Results: The first patient was enrolled in February 2007. A pre-planned interim analysis to evaluate the efficacy and safety was performed at 50% information. An independent central adjudication committee determined the assessment and timing of progressive disease prior to the interim analysis. At the interim analysis, it was determined by the Data Monitoring Committee (DMC) that the study had crossed the O'Brien Fleming superiority boundary for the primary endpoint, demonstrating a highly statistically significant improvement in PFS for patients treated with MPR compared with MP as first-line treatment for MM patients. The topline results will be availabel at the time of the meeting. Conclusions: MPR is an effective and safe regimen for front-line use in MM. PFS was significantly improved in patients who received MPR followed by lenalidomide maintenance compared with those who received MP followed by placebo maintenance. MPR followed by lenalidomide maintenance is a new therapeutic option and can be considered a new standard for patients older than 65 years old. Disclosures: Palumbo: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmion: Honoraria, Membership on an entity's Board of Directors or advisory committees. Off Label Use: Lenalidomide is not approved for first line use in multiple myeloma. Dimopoulos:Celgene: Honoraria. Delforge:Janssen-Cilag: Consultancy, Honoraria; Celgene: Honoraria, Speakers Bureau. Kropff:Ortho Biotech: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau. Foa:Celgene: Membership on an entity's Board of Directors or advisory committees. Yu:Celgene: Employment. Herbein:Celgene: Employment. Mei:Celgene: Employment. Jacques:Celgene: Employment. Catalano:Celgene: Research Funding.

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The Ki67/CD138 Ratio Independently Predicts Overall Survival in the Upfront Treatment of Newly Diagnosed Multiple Myeloma

Blood ◽

10.1182/blood.v124.21.2016.2016 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2016-2016

Author(s):

Tomer M Mark ◽

Peter Forsberg ◽

Ihsane Ouansafi ◽

Adriana C Rossi ◽

Roger N Pearse ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Overall Survival ◽

Board Of Directors ◽

Research Funding ◽

Complete Response ◽

Newly Diagnosed ◽

First Line ◽

Advisory Committees ◽

Line Therapy

Abstract Background: Assessment of malignant plasma cell cycling via plasma cell labeling index (PCLI) has been a validated prognostic tool in multiple myeloma (MM) but the test requires specialized technical expertise and is not widely available. Ki67 is a well-known protein marker of cellular proliferation on immunohistochemical (IHC) staining with prognostic utility in other malignancies. In an effort to develop a simpler system to provide analogous information to PCLI, we used a novel IHC co-staining technique for CD138 and Ki67 to quantify plasma cells in active cycling. We then performed a retrospective analysis of the ratio of Ki67/CD138 (Ki67%) in newly diagnosed patients with multiple myeloma receiving 1st-line therapy to correlate with clinical outcomes. Methods: A retrospective cohort study of patients (pts) with treated symptomatic MM was performed by interrogation of the clinical database at the Weill Cornell Medical College / New York Presbyterian Hospital. For inclusion in the analysis, subjects must have started first-line treatment in the period of 2005-2010, and had available bone marrow biopsies. Double-staining with Ki67 and CD138 was performed by IHC. The Ki67% was calculated as the percent of plasma cells expressing CD138 that were also found to express Ki67. Treatment outcomes were stratified and compared based on %Ki67. Response was determined by monthly serum protein electrophoresis / immunofixation (IFX) with free light chain analysis according to International Multiple Myeloma Working Group (IMWG) guidelines. Pts who were IFX negative but had no subsequent bone marrow biopsy were classified as being in unconfirmed complete remission. Results: We identified 151 patients with newly diagnosed MM and available %Ki67 expression who received first-line therapy over the period of 2005-2010. Patient were subdivided into two groups based on %Ki67: Low: %ki67 <= 5%, n = 87; and High: %Ki67 >5, n=64, to allow for comparison of treatment response and survival analysis. Specific therapeutic agent exposure history did not differ significantly between patients. Both groups had similar depth of response rates (ORR) to front-line therapy, Table 1. Median progression-free survival for the high versus low %Ki67 groups approached statistical significance at 54 months (95% CI 30.8,67.4) versus 26.9 months (95% CI 21.6,40.2), respectively (P = 0.083). At data cut-off, there were 30 deaths in the low %Ki67 group (1-yr OS 93%, 5-yr OS 71%) and 36 deaths in the high %Ki67 group (1-yr OS 94%, 5-yr OS 62%). Median overall survival (OS) was not reached for Ki67% <= 5% (95% CI 97.3,NR) vs. 78.9 months (95% CI 55.9,93.1) for Ki67% > 5%, (P = 0.0434), Figure 1. Multivariate cox regression for factors with influence on OS showed that only high-risk cytogenetics (HR 2.05, 95% CI 1.17, 2.92, P = 0.027), ISS (HR 1.835, 95% CI 1.33, 3.60, P = 0.000), and %Ki67 group status had an independent effect on survival outcome. Low (<=5%) versus high (>5%) %Ki67 influenced overall survival with a hazard ratio of 1.76 (CI 1.07,2.92, P = 0.027). Survival after ASCT was significantly longer in the low %Ki67 group with median OS not reached (95%CI, 97.3, NR) versus 86.9 months (95% CI 43.9, NR) for high %Ki67 group (P = 0.04). Discussion: The ratio of IHC double positive Ki67 and CD138 of > 5% is an independent prognostic marker for overall survival in newly diagnosed MM undergoing 1st line therapy. The %Ki67 serves as a simpler and widely available analog to PCLI that can be presently performed in most hematopathology laboratories. Table 1: First Line Treatment and Best Response (modified IMWG Criteria) Ki67% <= 5(N = 87)n (%) Ki67% > 5(N = 64)n (%) P Treatment Exposure* Lenalidomide 59 (67.8) 48 (75) 0.34 Thalidomide 30 (34.5) 14 (21.9) 0.09 Bortezomib 25 (28.7) 14 (21.9) 0.34 Alkylating agent 11 (12.6) 4 (6.3) 0.19 ASCT 27 (31) 22 (34.4) 0.66 Best Response Overall Response (>= Partial response) 77 (88.4) 57 (89.1) 0.41 Complete response 15 (17.2) 22 (34.4) Unconfirmed complete response** 14 (16.1) 8 (12.5) Very good partial response 23 (26.4) 15 (23.4) Partial response 25 (28.7) 12 (18.8) Stable disease 9 (10.3) 5 (7.8) Progressive disease 1 (1.2) 2 (3.1) * Percentages do not add to 100% due to instances of concurrent therapy use ** Unconfirmed complete response: immunofixation negative, but no confirmatory bone marrow biopsy available Figure 1 Overall Survival by %Ki67 Figure 1. Overall Survival by %Ki67 Disclosures Mark: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Research Funding, Speakers Bureau. Rossi:Celgene: Speakers Bureau. Pekle:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Perry:Celgene: Speakers Bureau. Coleman:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Honoraria. Niesvizky:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

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Efficacy of Lenalidomide in Patients with Multiple Myeloma Previously Treated by Melphalan-Prednisone and Thalidomide

Blood ◽

10.1182/blood.v120.21.4075.4075 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4075-4075

Author(s):

Jessica Michel ◽

Sabine Revuz ◽

Stéphanie Tardy ◽

Guillemette Fouquet ◽

Murielle Roussel ◽

...

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Response Rate ◽

Thromboembolic Events ◽

Line Treatment ◽

Efficacy And Safety ◽

First Line ◽

Advisory Committees ◽

Previously Treated ◽

First Line Treatment

Abstract Abstract 4075 Introduction. The association of Melphalan-Prednisone and Thalidomide (MPT) is approved as first-line treatment in elderly patients with Multiple Myeloma (MM). This treatment demonstrated significant benefit in terms of overall survival (OS) and Progression Free Survival (PFS) as opposed to MP alone. Lenalidomide (Len), used in combination with Dexamethasone (Len/Dex), is recommended to treat patients with relapsed MM who received a prior therapy. Len is an oral immunomodulator similar to Thalidomide (T). Both these drugs have identical activity but their safety profiles are different. So, in case of successive use of MPT and Len/Dex, it is legitimate to think that the efficacy of Len is affected by the previous use of T, probably because of the resistance to Len developed by relapsed or refractory patients. Therefore, we carried out a retrospective, multicentric study in order to assess the efficacy and safety of Len in patients with relapsed MM previously treated by MPT. Method. Our survey included 64 elderly patients with symptomatic MM from three French hematology centers. All the patients showed a relapsed MM treated with first-line treatment of MPT. Len was administered at first or second relapse. The main objective was to assess the efficacy of Len in terms of response rate, OS and PFS. Another objective was to evaluate the tolerance to Len and MPT treatments and to identify the predictive factors of efficacy of Len like the response rate, the duration of remission after MPT treatment and the line number of treatment before using Len. Results. The median age of patients at diagnosis was 73.5 years old and the sex ratio was 1. The M-protein was IgG for 64% of patients, IgA for 20%, light chains for 14% and IgD for 2%. Concerning the International Staging System, 35% of patients were stage I, 28% were stage II and 37% were stage III. MPT was administered with a 100mg/d thalidomide dose to 83% of patients. The median duration of T treatment was 13 months [range: 0.1 – 29.5]. The overall response rate (ORR) was 90% with 53% of partial response (PR), 27.5% of very good partial response (VGPR) and 9.5% of complete response (CR). Five patients stopped T because of progression on therapy, 36 because of toxicity out of which 26 because of peripheral neuropathy and 2 thromboembolic events. The median response duration after MPT was 25.5 months. Len was administered at first relapse to 47 patients (73.5%) and at second relapse for the others (n=17). The second-line treatment for these 17 patients was bortezomib-based regimen treatment. The daily dose of Len was 15 to 25 mg, always associated with low dose of Dex, for 83% of patients. Ten cycles of Len/Dex were administered on average. For 23/64 patients, the Len/Dex treatment is going on, 21/41 patients stopped because of progression and 17/41 because of toxicity (hematologic toxicity: 8/17, thromboembolic events: 2/17, general and gastrointestinal disorder: 7/17). The Len ORR was 78% (CR: 3.5%, VGPR: 27.5%, PR: 47%). The median SSP after initiation of Len is 12.8 months. The median OS after initiation of Len is 43 months and the OS rate is 58% at 3 years. Since the diagnosis, No predictive factor has a significant impact on the efficacy of Len. No second primary malignancies were reported. Conclusion. Our study shows that the efficacy and safety of Len is satisfactory, even after a Thalidomide treatment. The ORR and median PFS are similar to published data. There is no increase of toxicity for patients on Len, especially concerning thromboembolic events. With the development of new drugs like Carfilzomib, Pomalidomide and Eculizumab, the perspective of treatment increased as well as the number of lines. The choice of therapeutic sequences must be taken into account. In this study, we show that the MPT – Len/Dex sequence is effective and safe for elderly MM patients. Disclosures: Roussel: celgene: Honoraria; janssen: Honoraria. Attal:celgene: Membership on an entity's Board of Directors or advisory committees; janssen: Membership on an entity's Board of Directors or advisory committees. Leleu:celgene: Honoraria; janssen: Honoraria. Facon:onyx: Membership on an entity's Board of Directors or advisory committees; celgene: Membership on an entity's Board of Directors or advisory committees; janssen: Membership on an entity's Board of Directors or advisory committees; millenium: Membership on an entity's Board of Directors or advisory committees. Hulin:celgene: Honoraria; janssen: Honoraria.

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The Impact of Fractures on Survival in Multiple Myeloma: Results from a Population-Based Study

Blood ◽

10.1182/blood-2018-99-115403 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4490-4490

Author(s):

Sigrun Thorsteinsdottir ◽

Ingigerdur S Sverrisdottir ◽

Gauti Gislason ◽

Ola Landgren ◽

Ingemar Turesson ◽

...

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Research Funding ◽

Cox Regression ◽

Population Based ◽

Advisory Committees ◽

Population Based Study ◽

Risk Of Death ◽

Increased Risk ◽

The Impact

Abstract Introduction Multiple myeloma (MM) causes lytic bone lesions, osteopenia, and fractures, which increase the morbidity of MM patients. Results from small previous studies have indicated that fractures in MM have a negative effect on survival. Aims The aim of the study was to evaluate the impact of fractures on survival in MM patients diagnosed in Sweden in the years 1990-2013. Furthermore, to analyze the effect of bone fractures at MM diagnosis on subsequent survival. Methods Patients diagnosed with MM in 1990-2013 were identified from the Swedish Cancer Registry. Information on date of birth, diagnosis, and death were collected from the Registry of Total Population. Information on all fractures were retrieved from the Swedish Patient Registry. Cox regression model was used with fractures as time-dependent variables. The effect of fractures on survival was assessed for any fracture or a subtype of fracture (a specific bone fracture or ICD-coded pathologic fracture). Either first fracture or the first subtype of fracture was used in the analysis. The effect of a fracture at MM diagnosis (within 30 days before or 30 days after MM diagnosis) on survival was also estimated using a Cox regression model. All models were adjusted for age, sex, time of diagnosis, and previous fractures. Results A total of 14,008 patients were diagnosed with MM in the study period. A total of 4,141 (29.6%) patients developed a fracture including fractures that occurred within a year before MM diagnosis and thereafter. Hereof 2,893 (20.7%) patients developed a fracture after MM diagnosis. The risk of death was significantly increased for patients that developed a fracture after the time of MM diagnosis with a hazard ratio (HR) of 2.00 (95% confidence interval (CI) 1.91-2.10) for all fractures combined. The risk of death was significantly increased for patients that developed all subtypes of fractures after MM diagnosis except ankle fractures. The risk of death was significantly increased for patients that developed pathologic fractures (HR=2.17; 95% CI 2.03-2.32), vertebral fractures (HR=1.73; 95% CI 1.61-1.87), hip fractures (HR=1.99; 95% CI 1.82-2.18), femoral fractures (HR=2.62; 95% CI 2.32-2.98), humerus fractures (HR=2.57; 95% CI 2.32-2.86), forearm fractures (HR=1.24; 95% CI 1.05-1.46), and rib fractures (HR=1.52; 95% CI 1.31-1.77), but not for ankle fractures (HR 1.07; 95% CI 0.79-1.44). A total of 942 (6.7%) of all MM patients were diagnosed with a fracture within 30 days before or 30 days after MM diagnosis. The patients with a fracture at diagnosis were at a significantly increased risk of death compared to those without (HR 1.31; 95% CI 1.21-1.41; Figure) Conclusions Our large population-based study, including over 14,000 patients diagnosed with MM in Sweden in the years 1990-2013, showed that MM patients that developed a fracture after the time of diagnosis were at twofold increased risk of dying compared to MM patients without a fracture. Furthermore, MM patients with a fracture at diagnosis had a 30% higher risk of dying compared to patients without a fracture. Our results indicate that fractures in MM reflect a more advanced disease at diagnosis and stress the importance of managing MM bone disease in all MM patients. Figure. Figure. Disclosures Landgren: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy; Celgene: Consultancy, Research Funding; Amgen: Consultancy, Research Funding.

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Role of High-Dose Melphalan and Autologous Stem Cell Transplantation in Multiple Myeloma Patients Presenting with t(11;14)

Blood ◽

10.1182/blood-2019-129880 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4580-4580 ◽

Cited By ~ 1

Author(s):

Eduardo Sobejano ◽

Veronica Gonzalez De La Calle ◽

Victor Higuero ◽

Fernando Escalante ◽

Ramón García-Sanz ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Board Of Directors ◽

Research Funding ◽

University Hospital ◽

First Line ◽

Advisory Committees ◽

Baseline Characteristics ◽

Standard Risk

INTRODUCTION The t (11; 14) by fluorescent in situ hybridization (FISH) is found in 15-20% of patients with multiple myeloma (MM) . Although it was classically considered a standard risk translocation or even a good prognosis, recent studies conducted in the era of new drugs show contradictory results and it is not well established if they have to be considered intermediate or standard risk. The possibility of using targeted therapy with venetoclax for patients harboring t(11;14) makes the investigation of the outcome of newly diagnosed multiple myeloma (NDMM) with t(11;14) as relevant. METHODS We analyzed the baseline characteristics and outcome of patients with t(11;14)and receiving HDT-ASCT within the series of 647 patients with NDMM between 1988 and 2018 according to the current criteria at each moment at two academic hospitals in Spain (University Hospital of Salamanca and Hospital of Leon) . The FISH was performed on selected cells according to international regulations and centralized at the University Hospital of Salamanca. For this purpose, a descriptive cross-sectional study was first conducted comparing the characteristics of patients with t (11; 14) versus the rest. The final objective wasto evaluate the role of HDT-ASCT in NDMM with t(11;14). RESULTS The baseline characteristics of the whole series were: a median age of 71years (yrs) (range:30-96). 217 patients (33,5%) were under 65 years. 352 (56.2%) were IgG; 161 (25.7%) IgA; 87 (13.9%) Bence Jones; 19 (3%) non-secretors, and 5 and 2 cases were IgD and IgM, respectively. 320 (53.2%) received novel agents as part of the first line of therapy. Overall, 153 (27.8%) achieved complete response (CR) after first line, and 403 (73.1%) at least a partial response. After a median follow-up for living patients of 4.26 yrs (range: 0,1-27.3), the OS of the entire series was 2.74 years. T(11;14) was performed in 440 NDMM patients and was positive in 80 (18.2%). Only in 5 patients other high-risk alterations (t (14:16), t (4:14) or del17p (p53)) were detected. The baseline characteristics of patients with and without t (11:14) did not show significant differences, except for the heavy chain pattern(p <0,001). IgA was lower in patients with t(11:14) 12,8% (10 out of 78)vs 27,7% (98 out of 353). Of note, most patients with non-secretory MM (10 out of 16, 62,5%) had the t(11;14) whilst in the conventional secretory MM patients, t(11;14) was observed in 68out of 415(16,4%). In addition, the plasma cell bone marrow infiltration was significantly higher in patients with t(11;14)(> 60% Plasma Cells) 32.8% vs 13.3%(p <0.001)). HDT-ASCT was performed in 162 patients (25%)and 22 of them (13,5%) were positive for the t(11:14) and only in 2 patients, other high-risk alterations were detected.The induction therapy received in both treatments arms was homogeneous basically consisted on combinations of proteasome inhibitors plus immunomodulatory drugs. The median OS for NDMM patients undergoing ASCT was 4,33 years. (range: 0,47-26,85) and the median PFS for this patients was 2,25 yrs (range: 0,1-27,25) The median PFS for patients with t (11/14) undergoing ASCT trended to be higher than that observed in patients without t(11;14) who received also HDT-ASCT (99.1 vs 54.9 months), without obtaining significant results, (p 0.205) maybe due to the small number of patients (Figure 1).The median OS in the group of patients with and without t(11:14) undergoing ASCT was 120,8 vs 140 months (p= 0,829). In the cohort of non eligible ASCT patients both median PFS and OS for patients with t(11:14) was similar than that observed in patients without t(11:14)(median PFS of 19,9 vs 19,4 months) (p 0,438) and (median OS of 31,5 vs 44 months) (p 0,424), respectively. CONCLUSION T(11;14) seems to be a cytogenetic abnormality more frequently observed in patients with NDMM and non secretory phenotype what requires further investigation. Patients with t(11;14) benefit the most if they received HDT-ASCT and it would represent a therapeutic strategy of choice if the patient is transplant-eligible. Figure 1 Disclosures Puig: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding; The Binding Site: Honoraria; Takeda, Amgen: Consultancy, Honoraria. Mateos:Abbvie: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Pharmamar: Membership on an entity's Board of Directors or advisory committees; Janssen: 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; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria; EDO: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Racial Differences in High-Risk Cytogenetic Mutations and Outcomes in Multiple Myeloma

Blood ◽

10.1182/blood-2019-126304 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5494-5494

Author(s):

Ben A Derman ◽

Meytal Chernoff ◽

Andrzej Jakubowiak ◽

Brian C.-H. Chiu

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

High Risk ◽

Maintenance Therapy ◽

Board Of Directors ◽

Similar Distribution ◽

First Line ◽

Advisory Committees ◽

Blacks And Whites ◽

Pre Treatment

Introduction: Multiple myeloma (MM) is more common in blacks compared to whites. Prior studies have shown that when blacks have equal access to anti-myeloma therapies as whites, they have similar or even superior relative survival. However, most of these studies included eras when proteasome inhibitors (PI) and immunomodulatory agents (IMiD) were not routinely used. In addition, it is unclear how pre-treatment high risk cytogenetic mutations (HRCM) affect response to therapy among races. We sought to assess differences in the frequencies and outcomes between blacks and whites stratified by cytogenetic risk in two cohorts of MM patients receiving modern treatment approaches. Methods: A retrospective chart review was conducted using the Multiple Myeloma Research Foundation (MMRF) CoMMpass registry (version IA13) and the University of Chicago cytogenetic database and medical records (UChicago). High risk cytogenetic mutations were defined as: deletion 17p/TP53, 1q gain, t(4;14), t(14;16), and t(14;20). The CoMMPass registry inferred cytogenetic changes from next-generation sequencing data; a deletion required that 21% of cells have at least a 1 copy deletion, a gain required that 23% of the cells have a 1 copy gain, and translocations required at least 30% of cells having the event. UChicago cytogenetics data were limited to analyses using fluorescent in situ hybridization on CD138+ selected bone marrow aspirate samples. Abstracted data included pre-treatment demographics, International Staging System (ISS), cytogenetics, induction regimen, autologous stem cell transplant (ASCT) and maintenance therapy use, and overall survival (OS). Comparisons were made using Chi-square or Fisher's exact test for categorical variables and Mann-Whitney U-test for continuous variables. Kaplan-Meier curves were used to display survival curves and Cox models were used to assess the association between cytogenetic mutations and outcomes. Baseline HRCM frequencies from the MMRF and UChicago were pooled; outcomes from the MMRF registry are provided here, and combined survival analysis with UChicago data will be presented. Results: We identified 639 MM patients (113 black and 526 white) in the MMRF CoMMpass registry and 110 (47 black and 63 white) in the UChicago database with complete baseline cytogenetic data available. Median age was 64.5 yrs for whites vs 63 yrs for blacks (p=0.2); 349/589 (59%) whites and 93/160 (58%) blacks were male (p=0.9). There was a similar distribution in the number of HRCMs between the two groups (p=0.7), and no statistical differences in individual HRCMs. In analyzing outcomes in the MMRF cohort, blacks and whites had similar pre-treatment ISS stage and bone marrow plasmacytosis. Blacks were less likely to receive triplet therapies, including combined PI/IMiD-based or alkylator-based triplet therapy (55% vs 73%, p<0.001). First line ASCT was performed in 260/526 (49%) whites compared to 44/113 (39%) blacks (p=0.05). A triplet induction combined with first line ASCT was performed in 231/526 (44%) whites and 37/113 (33%) blacks (p=0.04). Of those who received ASCT, equal numbers received post-ASCT maintenance therapy (60% vs 59%, p=0.9). For the entire MMRF cohort, OS was shorter for blacks compared to whites (Hazard Ratio (HR) 1.59, 95% confidence interval (CI) 1.13-2.27, p=0.01) (Fig. 1A). Estimated 3-yr OS was 67% for blacks vs 76% for whites (p=0.05). In patients who specifically received a triplet regimen followed by ASCT (Fig. 1B), there was no difference in OS between races (HR 1.86, 95% CI 0.75-4.63, p=0.2). Among patients with no HRCM present at diagnosis, there was also no difference between races (p=0.6) (Fig. 2A). There was a trend toward inferior OS in blacks vs whites with one or more HRCMs, which did not reach significance (p=0.13) (Fig. 2B). Results from pooled analyses with the UChicago cohort will be presented at the ASH meeting. Conclusions: There was a similar distribution of HRCMs between blacks and whites. Utilization rates of both triplets and ASCT were higher for both races than previously reported; however, there was a higher use of triplet regimens and ASCT in whites vs blacks. Access to a combination of frontline triplet regimens and ASCT appears to mitigate disparities in outcomes for patients with standard risk cytogenetics, but it is unclear if this is true for those with HRCMs. This requires further investigation of the biological differences in MM among races. Disclosures Jakubowiak: Adaptive Biotechnologies: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; KaryoPharm Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; SkyLineDx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Juno: Consultancy, Honoraria; AbbVie: 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; BMS: 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.

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Final Results of a Phase II Study Evaluating Lenalidomide in Combination with Low Dose Dexamethasone As First Line Therapy for Primary Plasma Cell Leukemia

Blood ◽

10.1182/blood.v118.21.2925.2925 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2925-2925 ◽

Cited By ~ 5

Author(s):

Pellegrino Musto ◽

Fiorella D'Auria ◽

Maria Teresa Petrucci ◽

Anna Levi ◽

Nicola Cascavilla ◽

...

Keyword(s):

Renal Failure ◽

Board Of Directors ◽

Phase Ii ◽

Newly Diagnosed ◽

Cell Leukemia ◽

First Line ◽

Advisory Committees ◽

First Line Therapy ◽

Line Therapy ◽

Primary Plasma Cell Leukemia

Abstract Abstract 2925 Primary plasma cell leukemia (PPCL) is an aggressive variant of multiple myeloma, accounting for 0.5–4% of all newly diagnosed myeloma cases and characterized by a short survival (generally less than 1 year), which is only moderately improved by transplant procedures. Novel agents seem to be able to ameliorate the poor clinical outcome of both primary and secondary leukemic phases of myeloma; however, no data are currently available on the use of lenalidomide as first line therapy in PPCL. On March, 2009, we started a multicenter, phase II trial aiming to evaluate safety and antitumor activity of lenalidomide in combination with dexamethasone (LD) in previously untreated PPCL. Here we report the final results of this study. Newly diagnosed PPCL patients received lenalidomide at a dose of 25 mg/d for 21 days and oral dexamethasone at a dose of 40 mg on days 1, 8, 15, and 22 for each 28-day cycle. After 4 cycles, responding patients not eligible for stem cell transplantation (SCT) continued until 8 cycles of full-dose LD, if tolerated, followed by a maintenance dose of single agent lenalidomide equal to 10 mg/d on days 1–21 of each 28-day cycle. Patients responding after 4 cycles and eligible for SCT proceeded according to single Centre transplant policy. Patients not responding after 4 cycles or progressing during this treatment were considered off-study. The primary endpoint was early response rate according to International Uniform Criteria. The secondary endpoints were PFS, OS, safety and percentage of eligible patients able to undergo autologous or allogeneic SCT. Appropriate dose reductions, contraception methods and anti-thrombotic prophylaxis were applied. Twenty-three patients, as requested by the Simon Optimal Two-Stage Adaptive Design adopted, were enrolled. The trial was therefore closed on May, 31, 2011. M/F ratio was 0.7, mean age was 62 years (range 44–80). Circulating plasma cells ranged from 2.1 to 115 × 10e9/l. Moderate renal failure, increased LDH and extramedullary disease occurred in 39.1%, 43.5% and 13 % of patients, respectively. Hb was < 10 g/dl in 19 patients (82.6%), while platelet count was < 50 × 10e9/l in 5 patients (21.7%). Karyotype abnormalities were detected by FISH in 21 out of 22 tested patients; in particular, 1p loss was found in 9 patients, 1q gain in 10 patients, del(13q) in 16 patients, del(17p13) in 7 patients, t(11;14) in 7 patients, t(4;14) in 3 patients and MAF translocations, including t(14;20) and t(14;16), in 8 patients. Seventeen patients had a combination of two (n. 5) or more (n. 12) cytogenetic lesions. On intention-to-treat analysis, 14 patients completed the initial four planned cycles and all of them responded. In particular, 6 PR (26.1%), 4 VGPR (17.4%), 1 near-CR (4.3%) and 3 CR (13%) were achieved (ORR 60.8%, VGPR or better 34.7%). Causes of early treatment discontinuation were: a) progressive disease (4 patients, after an initial, brief response in 2 cases); b) severe adverse events (4 patients: one acute renal failure, one Stevens-Johnson's syndrome, one pneumonia suspected for Pneumocystis carinii etiology, one multi-organ failure); c) death in PR due to causes unrelated to treatment or disease (one patient). Other relevant non-hematological toxicities included four episodes of pneumonia and one case of DVT. Grade 3–4 hematological toxicities occurred in about half of cases, requiring Lenalidomide dose adjustments. So far, among subjects achieving a response after 4 LD cycles, 8 eligible patients have successfully collected peripheral blood stem cells: 5 of them have completed single or double autologous SCT, one patient received tandem autologous-allogeneic non myeloablative SCT from a MUD donor. All patients transplanted after LD are currently alive and in remission phase. The maintenance phase has been reached in 3 responding patients not eligible for SCT, 2 of whom have relapsed after 2 and 8 months, respectively. With a mean follow-up of 15 months, OS and PFS are 65.2% and 52.1%, respectively. LD is a possible initial therapeutic option for PPCL, particularly in patients who receive SCT after a short course of induction treatment. Caution is required to prevent and to manage renal and hematological toxicities, as well as infectious complications. Considering some previous results obtained with other novel agents, the combination of lenalidomide and bortezomib might be an appealing approach to investigate prospectively in PPCL patients. Disclosures: Musto: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Petrucci:Celgene: Honoraria. Cascavilla:Celgene: Honoraria. Di Raimondo:Celgene: Honoraria. Caravita:Celgene: Honoraria. Morabito:Celgene: Honoraria. Offidani:Celgene: Honoraria. Bringhen:Celgene: Honoraria. Boccadoro:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Palumbo:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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Allogeneic Hematopoietic Stem Cell Transplantation in First Line High Risk Multiple Myeloma Patients: Evolving Strategies with the Immunomodulating Drugs.

Blood ◽

10.1182/blood.v120.21.3116.3116 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3116-3116

Author(s):

Mauricette Michallet ◽

Mohamad Sobh ◽

Jean El-Cheikh ◽

Stéphane Morisset ◽

Anne Sirvent ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

High Risk ◽

Board Of Directors ◽

Induction Treatment ◽

High Dose ◽

First Line ◽

Advisory Committees ◽

Β2 Microglobulin

Abstract Abstract 3116 We evaluated in this study the efficacy and toxicity of a pilot tandem auto-HSCT strategy followed by reduced intensity conditioning (RIC) and allogeneic HSCT with the post-allo-HSCT introduction of bortezomib and donor lymphocyte infusion (DLI) in high risk multiple myeloma (MM) patients (Group1). We compared our results to those observed after traditional tandem auto-RIC-allo-HSCT without bortezomib after allo-HSCT (Group2). Groups 1 and 2 were compared to matched patients not receiving allo-HSCT from the IFM previous prospective studies. Matching variables were: diagnosis date, age, gender, β2 microglobulin, cytogenetics and induction treatment, the matching ratio was 1:3. Groups 1 & 2 included MM patients of age ≤ 65 years who previously received vincristine, doxorubicin and high-dose dexamethasone (VAD) or bortezomib plus dexamethasone (VD) as induction treatment followed by auto-HSCT. Only patients who achieved at least a partial response (PR) after auto-HSCT were included. Patients must have an HLA identical related or unrelated donor, and at least one of the following factors: β2 microglobulin level >3mg/L, del13, t(4;14) or del17p. The conditioning regimen combined fludarabine 30 mg/m2/d (d-5→d-1), busilvex IV 3.2 mg/kg/d (d-4, d-3) and ATG 2.5 mg/kg/d (d-2, d-1). GVHD prophylaxis consisted on cyclosporine A 3mg/Kg from day -1 with the addition of methotrexate at days 1, 3 and 6 in case of ABO incompatibility. In group1, by day 90 post-allo-HSCT, patients not in CR received 4 cycles of bortezomib 1.3 mg/kg (21 days cycle, on days 1, 4, 8 and 11); if the CR was not achieved, increasing doses of DLI were administered. Allo-HSCT groups included 25 patients (12 in group1 and 13 in group2), 18 males and 7 females with a median age of 51 years [28–67], there were 15 IgG, 6 IgA and 4 light chains MM. Fourteen (56%) patients had del13, 7 (28%) del17 and 17 (68%) had β2 microglobulin level >3mg/L. Induction treatment was VAD in 16 (64%) patients and VD in 9 (36%). Twenty-one (84%) patients received high dose melphalan (200 mg/m2) while the rest received a dose of 140 mg/m2; auto-HSCT was performed after a median time of 5.5 months [3.6–15.3] from diagnosis. The median time between auto-HSCT and allo-HSCT was 3.8 months [2.5–8.5]. The stem cell source was peripheral HSC in 22 (88%) of cases and the median number of infused CD34+ cells was 6.1×106cells/Kg (range: 2–13) from 16 identical siblings and 9 HLA (10/10) matched unrelated donors. Sex matching was as follow: F→M:9, F→F:3, M→F: 4 and M→M:9 and for ABO compatibility, 18 (72%) were compatible, 1 had minor incompatibility and 6 major incompatibility. At allo-HSCT, one patient was in CR, 4 in very good partial response (VGPR) and 20 patients were in PR. The matched population included 36 controls for group1 and 39 for group2. At Day 90 after allo-HSCT, all patients engrafted, 10 patients were in CR and 15 patients were in less than CR. Nine patients in group1 received bortezomib, 3 reached a CR while the 6 others were still in PR and received increasing doses of DLI. There were 8 acute GVHD [7 grade II (3 in group1) and 1 grade III in group1] and 11 chronic GVHD [3 lim. (all in group1) and 8 ext. (1 in group 1)]. No GVHD reactivation was observed after DLI. At the last follow-up, 14 patients are alive (9 in group1 and 5 in group2), 10 patients were in durable CR1 post-allo-HSCT and 4 patients in PR after DLI; 11 patients died (3 in group1: all from progression; 8 in group2: 5 from progression and 3 from TRM). After a median follow-up of 55 months [3–142], the median OS was not reached in group1 vs. 65 months (51-NR) in its matched patients (p=0.027); and it was 96 months (49-NR) in group2 vs. 91 months (32-NR) in its matched patients (p=0.77). The median PFS was 49 months (29-NA) in group1 vs. 25 months (21–35) in its matched patients (p=0.0045); and it was 31 months (22-NR) in group2 vs. 28 months (21–40) in its matched patients (p=0.0776). The encouraging results observed in group1, in terms of OS, PFS and toxicity are due to the introduction of IV busilvex and better ATG administration schedule in addition to the immunomodulating role of bortezomib in the elimination of the residual disease. In addition, we showed a good GVL effect after DLI with a durable stability of the disease without any important GVHD complication. According to our promising results, we should reconsider the allo-HSCT in the context of first line treatment for high risk MM patients. Disclosures: Nicolini: Novartis, Bristol Myers-Squibb, Pfizer, ARIAD, and Teva: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Attal:celgene: Membership on an entity's Board of Directors or advisory committees; janssen: Membership on an entity's Board of Directors or advisory committees.

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Treatment Patterns from 2009 to 2015 in Patients with Newly Diagnosed Multiple Myeloma in the United States: A Report from the Connect® MM Registry

Blood ◽

10.1182/blood.v128.22.4489.4489 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4489-4489 ◽

Cited By ~ 5

Author(s):

Robert M. Rifkin ◽

Rafat Abonour ◽

Brian G.M. Durie ◽

Cristina J. Gasparetto ◽

Sundar Jagannath ◽

...

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

The United States ◽

Treatment Patterns ◽

Second Line ◽

Newly Diagnosed ◽

First Line ◽

Advisory Committees ◽

Frequency Of Use ◽

The Us

Abstract Introduction: Between 2009 and 2015, use of novel therapies (immunomodulating drugs and proteasome inhibitors) in multiple myeloma (MM) increased. Regimens initiated during this time frame may help project near-term future treatment patterns. Connect® MM is the first and largest prospective, observational, US-based, multicenter disease registry designed to characterize treatment patterns and outcomes for patients (pts) with newly diagnosed MM (NDMM). Pts with NDMM were enrolled in 2 sequential cohorts from Sep 2009 to Apr 2016. This noninterventional registry did not prescribe or limit therapy choices. Study sites represented all census regions, with 89% and 11% split between community and academic sites, respectively. This allowed a reasonable generalizability to patterns for the US. Methods: Connect® MM enrollment was initiated in Sep 2009 at 250 community and academic sites. Pts were enrolled within 2 months of diagnosis. Cohort 1 enrolled 1493 NDMM pts from Sep 2009 to Dec 2011, and Cohort 2 enrolled 1518 NDMM pts from Dec 2012 to Apr 2016. Data were collected at a baseline visit and quarterly visits thereafter until death or discontinuation. The current analysis was conducted for the population of treated pts (N=2848) as of May 2016. This study examined recorded treatment choice of first-line regimen, maintenance therapy, and second-line regimen in 6-month intervals. Trends in regimens were graphically represented using "Tepee" plots (Srinivasan, Shankar. Resource Tepee. Patent US 7,495,673 B1. 24 Feb 2009). Briefly, all pts who initiated treatment during each 6-month interval are represented horizontally, with each horizontal line indicating 100% of all treatment used in that period. The regimens are represented by gray shading with wider bands signifying the more frequently used regimens at each time interval. Results: Median follow‐up for all pts was 39.3 months (0.03‐78.4) in Cohort 1 and 15.4 months (0.2-40.1) in Cohort 2. For the treated population, the median age was 67 years (range 24‐94), 58% were male, 83% were white, and 38% of those reporting International Staging System stage had stage III MM. By US geographical region, 329 (11.6%) pts were from the Northeast, 1036 (36.4%) from the Midwest, 1117 (39.2%) from the South, 360 (12.6%) from the West, 4 (0.1%) from Puerto Rico, and 2 missing (0.05%). Most pts (2285; 80.2%) were from community sites, and 397 (13.9%) were from academic sites with the remaining from government sites. A total of 1416 (47.4%) reported an intent to transplant (stem cell transplant [SCT]) at the initiation of therapy. A total of 666 (25.8%) have progressed and entered second line. Tepee plots of treatment patterns for start of induction for those pts with and without SCT intent are provided in Figure 1A and 1B, respectively. The year 2012 does not feature in these induction plots, as this period corresponds to a time when pts were not enrolled-Cohort 1 had been completed and Cohort 2 had not yet opened. The 4 most common induction regimens for SCT intent, from left to right, in order of decreasing frequency of use, were lenalidomide (R), bortezomib (V), dexamethasone (D) combined (RVD); VD; cyclophosphamide plus VD (CyBorD); and RD. The 5 most common induction regimens for those without SCT intent, from left to right, in order of decreasing frequency of use, were VD, RD, RVD, CyBorD, and V. Triplet therapy in first-line induction pts increased in frequency from 2009 to 2014. The 4 most frequent maintenance regimens for those with SCT intent were R monotherapy, V monotherapy, RD, and RVD. The 4 most common maintenance regimens for pts who did not intend to receive SCT were R monotherapy, RD, VD, and V monotherapy. The most prevalent regimens in the second line were VD, RD, V, and RVD. Additional graphs including treatment patterns by age group (≤ 70 vs > 70 years) and maintenance by conduct of first-line SCT will be presented. Conclusions: Our work utilizes Tepee plots to outline induction and maintenance treatment patterns over time, for both SCT and non-SCT intent pts, using the largest, prospective, noninterventional registry study in the US. Triplet therapy use increased in the time period studied, with RVD being the most frequently used triplet for pts with or without SCT intent. The most common maintenance regimens included R as monotherapy or in combination. Disclosures 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/ONYX: Membership on an entity's Board of Directors or advisory committees. Abonour:Celgene: Membership on an entity's Board of Directors or advisory committees. Durie:Amgen: Consultancy; Janssen: Consultancy; Takeda: Consultancy. Gasparetto:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria. Jagannath:Bristol-Myers Squibb: Consultancy; Celgene: Consultancy; Merck: Consultancy. Terebelo:Celgene: Membership on an entity's Board of Directors or advisory committees. Toomey:Celgene: Consultancy. Kitali:Celgene: Employment, Equity Ownership. Zafar:Celgene: Employment. Srinivasan:Celgene: Employment; Individual Patent: Patents & Royalties: US7,495,673B1 Used for MM-Connect Treatment Patterns Abstract.. Hardin:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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