Exploration of Survival Stratification of Patients with Multiple Myeloma after First Relapse Using Real World Data

Abstract Risk stratification tools in multiple myeloma (MM), such as the International Staging System (ISS) and the revised-ISS (R-ISS), have improved understanding of survival expectations using the strongest known predictors at time of diagnosis. Given their value at diagnosis, these have been used to define risk after first relapse in clinical trials and standard practice. Although these tools have not been validated in this setting, their use arises because of the need to better characterize patients in order to define survival expectations and treatment decisions. Once the patient has relapsed, there are additional variables that may need to be considered in order to systematically assess patient risk, understand drivers of disease progression and ensure that treatment strategies are aligned with patient risk. Using data from the Czech Registry of Monoclonal Gammopathies (RMG), this study assessed predictors of overall survival (OS) and developed a new Risk Stratification Tool (RST) to predict OS at time of treatment decision after first relapse (TTD1). The RST was developed by estimating the strongest predictors of OS at both diagnosis and TTD1 to define the final parameters for inclusion. The cut-offs for each parameter reflect conventional cut-offs used in clinical practice and some were supported by evidence using a K-adaptive Partitioning for Survival (KAPS) approach, which stratified data based on distinct survival expectations. The hazard ratio (HR) of the selected predictors was used to assign a score per parameter at a patient level where missing data were entered with a contribution equal to 1. Using the full RMG data set at TTD1 (N=1418) the (KAPS) method was run to define 4 distinct group of patients based on survival expectations. The RST consists of 4 dimensions and 12 item questions based on the strongest predictors of survival at TTD1, "Patient Factors" (age and Eastern Cooperative Oncology Group (ECOG) performance status), "Existing Stratification Factors (R-ISS at diagnosis and ISS at TTD1), "Disease Factors" (calcium level, number of bone lesions, extramedullary disease, thrombocyte count, clonal cells in bone marrow aspiration cytology, lactate dehydrogenase [LDH]) and "Treatment history" (refractory to prior therapy, time-to-next-treatment [from initiation of treatment of first anti-myeloma drug to initiation of treatment at first relapse]) (Table 1). Subsequently, we explored each group based on distribution of frailty-driven measures (age and ECOG) and aggressiveness of the disease (rest of parameters) to understand what is driving stratification. Figure 1 shows the KM curve of survival after TTD1 for each of the 4 groups estimated by KAPS. The new analysis shows strong differentiation in survival expectations between the 4 groups (Table 2), showing significantly different OS for all groups compared with reference. The median OS and Confidence Intervals per group did not overlap, supported by the positive association of HR across groups. The distribution of the Total Score (Figure 2) is between 1 and 2, which shows sufficient sensitivity to differentiate these groups by survival expectations. The RST can then be split into Frailty Score and Aggressiveness Score (Figure 3a & b) to understand what is driving disease severity. The distribution of these two scores shows that group 1 consists of low patient frailty and low disease aggressiveness, whereas group 4 shows high on both elements. Group 2 has an increased score for frailty and marginal increase in aggressiveness compared with group 1, and group 3 stratification is driven by an increase in aggressiveness over group 2. The analysis showed that predictors, patient's experience of prior treatment and level of disease impact at the point of treatment decision after first relapse provided an initial framework to demonstrate strong differentiation between groups based on patient severity and what is driving patient risk (patient frailty vs aggressiveness of disease). The RST has shown promising results when applied to the RMG, however further validation of this work is required using other real-world and clinical trials data. Nevertheless, this analysis is a first step in systematically assessing patient risk to improve the selection of treatments based on improved understanding of patient profiles. Disclosures Hájek: Amgen: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; BMS: Honoraria; Takeda: Consultancy; Celgene: Consultancy, Research Funding. Bouwmeester:Amgen: Consultancy. Treur:Amgen: Consultancy. DeCosta:Amgen: Employment, Other: Holds Amgen Stock. Campioni:Amgen: Employment, Other: Holds Amgen Stock. Delforge:Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Raab:BMS: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Research Funding; Amgen: Consultancy, Research Funding. Schoen:Amgen: Employment, Other: Holds Amgen Stock. Szabo:Amgen: Employment, Other: Holds Amgen Stock. Lucie:Amgen: Consultancy. Gonzalez-McQuire:Amgen: Employment, Other: Holds Amgen Stock.

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Patient-Specific Risk Factors Independently Influence Survival in Myelodysplastic Syndromes in an Unbiased Review of EHR Records

Blood ◽

10.1182/blood-2019-122400 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5440-5440

Author(s):

Travis Spaulding ◽

Nicholas Strayer ◽

Andrew Sochacki ◽

Shannon Stockton ◽

Alexander Silver ◽

...

Keyword(s):

Risk Factors ◽

Board Of Directors ◽

Research Funding ◽

Health Record ◽

Comorbid Conditions ◽

Comorbid Disease ◽

Advisory Committees ◽

Study Population ◽

Group 2 ◽

Group 1

Background: Myelodysplastic syndromes (MDS) are clonal hematologic neoplasms stratified by risk by the international prognostic scoring system (IPSS) and IPSS-revised (IPSS-R) which measure risk by morphologic dysplasia, clinical cytopenias, blast count, and cytogenetic abnormalities. (PMID: 9058730, 22740453) The IPSS/IPSS-R do not consider clinical comorbid conditions, though MDS patients with higher burden of comorbid disease have higher rates of non-leukemic death, particularly those with cardiovascular and pulmonary disease. (19324411) Despite this, there has been limited investigation into how specific comorbid conditions may help define subgroups of patients with MDS. Methods: We identified 2676 cases of MDS as defined by ICD-9 code (238.72 - 238.75) in Vanderbilt's Synthetic Derivative (SD). The SD is a de-identified electronic health record (EHR) of over 2.2 million patients with a companion biorepository of DNA (BioVU) for a subset of these patients, including all of the patients with MDS. The 2676 cases were matched by age, gender, race, burden of comorbidities in EHR, and age at last appointment in EHR with 5287 controls. ICD-9 codes for other myeloid disease (e.g., myeloproliferative neoplasms, acute myeloid leukemia) or history of hematopoietic stem cell transplant were excluded among the controls. Characterization of comorbidities, via phecode analysis, was conducted on all cases and controls. Phecodes are groups of related ICD-9 codes describing a clinical syndrome or medical problem, previously demonstrated to be useful in phenome-wide associated studies in EHRs. (28686612) A case was defined as having a phecode only if a representative ICD-9 code was present on two distinct days in the EHR. Next, a cluster analysis of the study population and their associated comorbidities, via a bipartite stochastic block model, was completed, and the study population was organized into hierarchical structure based upon the similarities in comorbidity patterns among patients. Results: ICD-9 codes from the study population made up 181 phecodes, which were found in hierarchical cluster analysis to further cluster into 54 sub-groups and 16 larger groups. MDS patients clustered throughout all groups, the majority of which contained control patients; yet some MDS cases sub-clustered into groups that included a majority of MDS cases and these were further analyzed. Notably, two groups had equivalent size and MDS status were found to have significant differences in phecode profiles. Group 1 had 795 total patients with 783 MDS cases (98.5%) and Group 2 had 769 total patients with 684 MDS cases (88.9%), as per Fig 1a. There were no significant difference in sex between the two groups. Group 1 patients were significantly younger than Group 2 patients (58.3y vs 62.9y; p = 1.36 x 10-7), yet tended have increased risk of renal, cardiovascular and thromboembolic disease than Group 2, as per Fig 1b. Additionally, a higher proportion of Group 2 patients (695/769 or 90.4%) were alive at time of data extraction than Group 1 patients (451/795 or 56.7%) (OR 4.51, p = <2.2 x 10-16). Conclusions: By performing a phenome-wide analysis of patients with MDS in a large electronic health record (EHR), we reveal specific subgroups of MDS patients with distinct comorbidities and different survival, not affected by age or sex. This study demonstrates the ability to study comorbid conditions of MDS patients in an unbiased fashion, independent of disease specific risk factors that inform IPSS-R and which have historically been most important in stratifying risk in MDS. The role of comorbidity is instinctually clear to the adroit clinician, and this technique could provide distinct comorbid disease patterns which impute risk, or perhaps etiology in MDS. Disclosures Savona: TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm Therapeutics: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Selvita: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sunesis: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Patents & Royalties; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees.

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A Randomized Phase 2 Trial Comparing Carfilzomib-Dexamethasone Vs Observation As Maintenance after Induction with Carfilzomib-Cyclophosphamide-Dexamethasone in Salvage ASCT in Multiple Myeloma: A Trial By the Nordic Myeloma Study Group

Blood ◽

10.1182/blood-2019-122141 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 601-601 ◽

Cited By ~ 1

Author(s):

Henrik Gregersen ◽

Valdas Peceliunas ◽

Kari Remes ◽

Fredrik H. Schjesvold ◽

Niels Abildgaard ◽

...

Keyword(s):

Multiple Myeloma ◽

Maintenance Therapy ◽

Board Of Directors ◽

Research Funding ◽

Observation Group ◽

Phase 2 ◽

Advisory Committees ◽

Phase 2 Trial ◽

First Relapse ◽

Maintenance Group

Background: Salvage autologous stem cell transplantation (ASCT) is used in selected patients with relapsed multiple myeloma after up-front ASCT. However, there are limited data on the optimal induction therapy before salvage ASCT. There is strong support for the use of maintenance therapy after upfront ASCT in newly diagnosed multiple myeloma whereas data on maintenance therapy after salvage ASCT are sparse. The Nordic Myeloma Study Group (NMSG) initiated the CARFI trial (NCT02572492), an open randomized phase II study, to investigate the efficacy and safety of carfilzomib as part of induction and conditioning in salvage ASCT and to evaluate the role of carfilzomib/dexamethasone maintenance after salvage ASCT. Methods: Patients with first relapse after up-front ASCT were treated with an induction regime containing four cycles of CAR-CY-DEX (iv carfilzomib 20 mg/sqm → 36 mg/sqm on days 1, 2, 8, 9, 15 and 16, tablet cyclophosphamide 300 mg/sqm on days 1, 8 and 15 and tablet dexamethasone 20 mg on days 1, 2, 8, 9, 15 and 16 in each 28-days cycle). The subsequent conditioning regimen contained iv carfilzomib 27 mg/sqm on day -2 and -1, and iv melphalan 200 mg/sqm on day -2. The patients had not received any maintenance therapy after upfront ASCT. Two months after ASCT patients were randomized (1:1) to observation or maintenance therapy with iv carfilzomib 27 mg/sqm → 56 mg/sqm every second week and tablet dexamethasone 20 mg every second week. The randomization was stratified according to relapse 1 - 2 year or > 2 years after up-front ASCT, ISS stage and standard versus high-risk cytogenetics. Primary endpoint was comparison of time to progression (TTP) after up-front ASCT and TTP after salvage ASCT with CAR-CY-DEX induction. Another primary endpoint was to compare TTP between carfilzomib-dexamethasone maintenance and observation in patients treated with salvage ASCT. Results: 200 patients were enrolled in the study and 32 of these went off study during the induction and after ASCT. The remaining 168 patients were randomized to carfilzomib-dexamethasone (82 patients) or observation (86 patients). The median age was 62 (interquartile range: 56; 66) years and the median follow-up from time of inclusion was 20.1 (14.1 - 27.6) months. The median TTP after up-front ASCT was 33.2 (31.0-37.8) months compared with 28.1 (24.9-31.5) months after salvage ASCT. The two groups randomised to maintenance therapy or observation were balanced regarding age, time from myeloma diagnosis, treatment at diagnosis, performance status, ISS stage and high-risk cytogenetics (Table 1). The median TTP from randomisation was 28.8 (95% CI: 24.4-NR) months in the maintenance group and 18.5 (95% CI: 14.3-22.0) months in the observation group (hazard ratio 0.42 (95% CI: 0.26-0.68, P = 0.0003)) (Figure I). For the maintenance group TTP from inclusion was 35.4 (30.9-NR) months compared with TTP of 31.3 (29.4-37.8) months (P = 0.71) after up-front ASCT for these patients. A total of 53 serious adverse events (SAE) were reported in 25 patients on carfilzomib-dexamethasone maintenance and 33 SAEs in 21 patients in the observation group. The majority of the SAEs were infections; 39 in the maintenance group and 25 in the observation group, divided into viral infection (10 versus 3), septicemia (2 versus 0) and pneumonia (12 versus 7). Three SAEs classified as cardiac-pulmonary were observed in the maintenance group (syncope, atrial fibrillation and pulmonary embolism) in contrast to three in the observation group (atrial fibrillation and dyspnea(2)). Conclusion: In this randomized phase 2 trial, maintenance therapy with carfilzomib and dexamethasone prolonged median TTP with approximately 10 months following salvage ASCT in multiple myeloma. The difference between TTP after upfront ASCT and TTP after salvage ASCT with carfilzomib based induction therapy was small which supports the use of salvage ASCT followed by maintenance in selected patients at first relapse. Disclosures Remes: Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Other: Congress Support; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Congress Support; Amgen: Other: Congress Support; Celgene: Other: Congress Support; Sanofi: Other: Congress Support. Schjesvold:Janssen: 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; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; MSD: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; SkyliteDX: Honoraria; Oncopeptides: Membership on an entity's Board of Directors or advisory committees. Abildgaard:Amgen: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Takeda: Research Funding. Vangsted:Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Jansen: Honoraria. Blimark:Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees.

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RAEB-1 with Erythroid Hyperplasia and Erythroleukemia Share Clinico-Biological Features and Outcome: A Same Disease with Different Labels?

Blood ◽

10.1182/blood.v126.23.2866.2866 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2866-2866

Author(s):

Xavier Calvo ◽

Leonor Arenillas ◽

Mar Tormo ◽

David Valcárcel ◽

Elisa Luño ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

De Novo ◽

Erythroid Cell ◽

Advisory Committees ◽

Biological Features ◽

Erythroid Hyperplasia ◽

Group 2 ◽

Group 1 ◽

Who 2008

Abstract Introduction: Based on the 2008 World Health Organization classification (WHO 2008), erythroleukemia is defined by the presence of ≥50% erythroid precursors in bone marrow (BM) and ≥20% myeloblasts in the non-erythroid cell population. Multilineage dysplasia is almost always present with high rates of MDS-like cytogenetic abnormalities, specially complex karyotypes. Therefore an extensive comparison with myelodysplastic syndromes (MDS) with ≥50% erythropoesis seems crucial to elucidate whether erythroleukemia and MDS with erythroid hyperplasia should be considered as different biological entities. Aim: To elucidate this issue, the outcome and cytogenetic alterations of erythroleukemia patients were studied and compared to MDS patients with ≥50% erythropoesis with <5% BM blasts (RA, RARS, CRDM, MDS-U) or those with ≥5%-<10% (RAEB-1). In this subset of patients, the diagnosis of RAEB-2 is not possible because those with ≥50% erythropoesis and ≥10% BM blasts were formally diagnosed with erythroleukemia when the blast percentage was assessed in the non-erythroid cell population. Methods: We retrospectively analyzed 448 de novo MDS with ≥50% erythropoesis and 59 de novo erythroleukemias from the MDS Spanish registry (RESMD). Diagnosis was done according to WHO 2008 and patients with ≥80% erythropoiesis with less than 20% of myeloblasts in the non-erythroid cell compartment were excluded assuming a diagnosis of pure erythroid leukemia. Results: Median age of presentation was 74 years (25-94 years), median follow-up was 29.4 months, 63% were males. Median overall survival (OS) of MDS patients with ≥50% erythropoiesis and <5% of BM blasts (n=389; group-1) was significantly longer than MDS with ≥50% erythropoiesis and ≥5%-<10% (n=59; group-2/RAEB-1) (69 months vs. 18 months, p <0.001). Although erythroleukemia patients (n=59) presented a shorter median OS than group-1 patients (69 months vs. 14.5 months, p <0.001), there was no significant differences compared to group-2 patients (RAEB-1) (18 months vs. 14.5 months, p =0.679). Figure 1. Percentage of abnormal karyotypes was significantly higher in the group-2 and EL vs. group-1 but there was no significant differences between group-2 and erythroleukemia (56.9% vs. 44.1%, p =0.165). Moreover no significant differences were observed in the percentage of high-risk karyotypes defined by the IPSS (complex karyotype, chromosome 7 abnormalities) between RAEB-1 and erythroleukemia (30.5% vs. 23.7%, p =0.408). Finally, the presence of a high-risk IPSS karyotype was capable to discriminate two risk groups in the subset of patients with ≥5% BM blasts (RAEB-1 and erythroleukemia). Figure 2. Conclusion: Erythroleukemia and RAEB-1 with ≥50% erythropoiesis share clinico-biological features and outcome. Our findings suggest that erythroleukemia is a continuum of MDS with erythroid hyperplasia and karyotype rather than an arbitrary blast cut-off is the main prognostic marker in this subset of patients. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Valcárcel: Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Díez-Campelo:Celgene: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Janssen: Research Funding. Ramos:GlaxoSmithKline: Honoraria; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria; Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria.

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Daratumumab with Pomalidomide and Dexamethasone at First Relapse in Relapsed and/or Refractory Multiple Myeloma (RRMM) Patients

Blood ◽

10.1182/blood-2021-151161 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1616-1616

Author(s):

Nisha Joseph ◽

Kathryn T. Maples ◽

Kevin Hall ◽

Vikas A Gupta ◽

Larry H. Boise ◽

...

Keyword(s):

Multiple Myeloma ◽

Education Research ◽

High Risk ◽

Board Of Directors ◽

Research Funding ◽

Cell Transplant ◽

Advisory Committees ◽

First Relapse ◽

Standard Risk ◽

Privately Held

Abstract Background: Despite significant advances in therapeutic options for multiple myeloma (MM) patients, there is an ongoing need to identify effective treatment strategies in the relapsed space. The efficacy of daratumumab, pomalidomide and dexamethasone (DPD) in relapsed and/or refractory patients has been demonstrated in clinical trials, but there is limited data at first relapse in a real world setting. Here, we present a retrospective analysis utilizing our institutional data of multiple myeloma patients treated with DPD at first relapse at the Winship Cancer Institute of Emory University. Methods: Ninety relapsed and/or refractory myeloma (RRMM) patients were identified who had received only one prior line of therapy and subsequently treated with DPD at first relapse. Dose-adjustments were made based on the treating physician's discretion and patient tolerability. Demographic and outcomes data for the patients were obtained from our IRB approved myeloma database and responses were evaluated per IMWG Uniform Response Criteria. Results: The median age of this cohort was 61.9 years (range, 38-85). Other notable patient characteristics include: M/F 44.4%/55.6%; W/AA/Asian 50%/46.7%/3.3%; ISS I/II/III 28.9%/31.1%/20%; Isotype IgG/IgA/FLC 62.2%/17.8%/16.7%; standard risk/high risk 21.1%/52.2%. High risk disease was defined as the presence of t(4;14), t(14;16), del(17p), and/or complex karyotype. A total of 69 patients (76.7%) underwent autologous stem cell transplant (ASCT) upfront after attaining at least a partial response with induction therapy. The most common induction regimen was RVD (78.9%). 81.1% of patients received maintenance therapy, with 50.5% receiving single-agent lenalidomide maintenance and 72.2% receiving a lenalidomide-based maintenance regimen (RVD: 8 pts; Rd: 4 pts; IRD: 7 pts, KRD: 1 pt). With a median follow up of 72 months, the median OS from diagnosis was 158.6 months (95% CI 126.7-190.5) for the entire cohort. The median PFS from time of initiation of DPD was 15.6 months (95% CI 9.9-21.2), and the median OS from time of initiation of DPD was 41.3 months. For high risk vs standard risk patients, the mPFS from time of initiation of DPD was 7.2 months (95% CI 3.6-10.7) vs 17.6 months (95% CI 10.9-24.3), respectively. Median PFS2 in patients <2 years and >2 years from transplant was 8.6 months vs NR, respectively. Conclusions: These results illustrate the activity of DPD at first relapse in a predominantly len-refractory RRMM cohort of patients with impressive long-term outcomes. This benefit was particularly demonstrated in patients with time to relapse of >2 years post-transplant. Figure 1 Figure 1. Disclosures Joseph: GSK: Honoraria; BMS: Research Funding; Takeda: Research Funding; Karyopharm: Honoraria. Boise: AstraZeneca: Honoraria, Research Funding; AbbVie/Genentech: Membership on an entity's Board of Directors or advisory committees. Hofmeister: BlueBird Bio: Other: Non-CME speaker; Aptitude Health: Other: Non-pharma speaker for education, research, marketing; Verascity: Other: Non-pharma speaker for education, research, marketing; TRM Oncology: Other: Non-pharma speaker for education, research, marketing; DAVA Oncology: Other: Non-pharma speaker for education, research, marketing; Medscape: Other: Non-pharma speaker for education, research, marketing; Amgen: Other: Non-CME speaker; BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Philips Gilmore: Other: CME speaker; Non-pharma speaker for education, research, marketing; BioAscend: Other: CME speaker; Imbrium: Membership on an entity's Board of Directors or advisory committees; Myeloma360: Membership on an entity's Board of Directors or advisory committees; Genzyme: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Local PI of CST; Oncolytics: Other: National PI for CST; PI or co-PI IST; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Other: Local PI of CST; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Local PI of CST; Nektar Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Local PI of CST; BMS/Celgene: Other: National PI for CST; PI or co-PI IST; Local PI of CST; Sanofi: Other: National PI for CST; PI or co-PI IST; Ohio State University: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: IP rights, Patents & Royalties. Kaufman: Incyte, TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sutro, Takeda: Research Funding; Roche/Genetech, Tecnopharma: Consultancy, Honoraria; Fortis Therapeutics: Research Funding; Heidelberg Pharma: Research Funding; BMS: Consultancy, Research Funding; Amgen: Research Funding; Tecnofarma SAS, AbbVie: Honoraria; Incyte, celgene: Consultancy; Janssen: Honoraria; Novartis: Research Funding; Genentech, AbbVie, Janssen: Consultancy, Research Funding. Lonial: Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Merck: Honoraria; AMGEN: Consultancy, Honoraria. Nooka: GlaxoSmithKline: Consultancy, Other: Travel expenses; Amgen: Consultancy, Research Funding; Oncopeptides: Consultancy; Janssen Oncology: Consultancy, Research Funding; Sanofi: Consultancy; Karyopharm Therapeutics: Consultancy; Takeda: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy; Adaptive technologies: Consultancy.

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Acute Myeloid Leukemia with Myelodisplasia-Related Changes (AML-MRC) Defined Only By Morphological Findings May Not Represent a Poor Prognosis AML

Blood ◽

10.1182/blood-2019-129153 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2612-2612

Author(s):

Ana Pérez ◽

Olga Salamero ◽

Helena Pomares ◽

Maria Julia Montoro ◽

Montserrat Arnan Sangerman ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Myeloid Leukemia ◽

Research Funding ◽

Poor Prognosis ◽

Advisory Committees ◽

Group 3 ◽

Group 2 ◽

Acute Myeloid ◽

Group 1

According to the 2016 WHO classification, AML-MRC encompasses an heterogeneous group of acute myeloid leukemias (AML) comprising: AML emerged from a previous myelodysplastic syndrome (MDS) or myeloproliferative /myelodysplastic disease (group 1), AML with MDS-defining cytogenetic abnormalities (group 2), or acute myeloid leukemia (AML) with dysplasia in at least 2 cell lineages without the above mentioned (group 3). In spite that AML-MRC has been considered a high-risk entity with poor prognosis, little is known on the relationship of clinical and biological characteristics with outcomes in these three groups. The aim of this study was to describe the clinical and biological characteristics of patients with AML-MRC and analyze their prognostic variables and outcomes. We retrospectively analyzed AML-MRC cases diagnosed between January-2009 and December- 2018 in two institutions. Descriptive variables were studied to compare the three AML-MRC groups. AML cytogenetic risk and response were defined according to the European Leukemia Net recommendations. Overall survival (OS) was considered as the time from the diagnosis to the last visit. Survival analysis were performed with Kaplan Meier method and comparisons with the log-rank test. Among 575 cases of AML identified, 186 (32.3%) met AML-MRC criteria and were included in the study. The main patient characteristics are shown in Table1. Median age was 72 (range, 22-88) years and 32% were female. Adverse karyotype was present in 29% of patients, being more prevalent in the AML-MRC group 2. Sixty one patients (33%) received an intensive chemotherapy approach and 36 (19%) an allogeneic stem cell transplantation. Patients in group 3 exhibit a higher probability of achieving a complete response than groups 1 and 2 (Table 2). After a median follow-up for survivors of 28.5 months (range, 5-130), 149 (80%) died in this period. Three years Overall Survival (OS) for patients in groups 1, 2 and 3 was 3 (0-117), 5 (0-93) and 10 (0-130) months, respectively (p=0.012) (Figure 1). Type of treatment (intensive, non intensive or best supportive care) and cytogenetic risk also showed impact on OS. Multivariant analysis adjusting these factors showed that patients in group 3 also presented better OS than patients in group 1 (HR=0,42 [IC95% 0,18-0,84], p=0,02), both with around a 30% of patients with adverse cytogenetics. To conclude the present study suggests that group 3 of AML-MRC, for which the diagnosis is based solely on morphologic findings, showed better prognosis than the other groups. A more detailed molecular characterization might contribute to improve prognostic stratification of this heterogeneous AML entity, particularly in patients with non-high risk cytogenetics. Disclosures Salamero: Pfizer: Honoraria; Daichii Sankyo: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Valcárcel:Jazz Pharmaceuticals: Honoraria; Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other: spouse is an employee in the company, Speakers Bureau; Pfizer: Honoraria. Bosch:AstraZeneca: Honoraria, Research Funding; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

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Improved Treatment Outcomes for Patients with Hodgkin Lymphoma Relapsing after Autologous Hematopoietic Stem Cell Transplantation in the Brentuximab Vedotin Era - the Real-Life Report from the Polish Lymphoma Research Group

Blood ◽

10.1182/blood-2019-130484 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5276-5276

Author(s):

Anna Czyz ◽

Anna Lojko-Dankowska ◽

Agnieszka Giza ◽

Monika Dlugosz-Danecka ◽

Wojciech Jurczak ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Salvage Chemotherapy ◽

Brentuximab Vedotin ◽

Salvage Treatment ◽

Study Group ◽

Advisory Committees ◽

Historical Group ◽

Group 2 ◽

Group 1

Background Brentuximab vedotin (BV) is an effective salvage treatment in patients with relapsing/progressive Hodgkin lymphoma (HL). However, it is unclear how much BV improved the outcome of BV naïve patients who relapsed after autologous hematopoietic stem cell transplantation (autoHCT) in real life. To address this question, we compared the outcome of patients who received conventional salvage treatment before the BV era to those who were treated with BV in haematological centres allied within the Polish Research Study Group. The goals of the study were to compare: the response rates to the conventional salvage chemotherapy and to the BV-based treatment, the proportion of patients proceeding to subsequent allogeneic (allo) or second autologous HCT and finally the overall survival (OS), and progression-free survival (PFS) of relapsing patients after autoHCT treated with and without BV. Methods and study group The study group consisted of adult patients with classical HL relapsing after first autoHCT who were treated either with conventional salvage chemotherapy (between 2001 and 2013; Group 1, n=121) or BV based treatment (between 2012 and 2018; Group 2, n=44). The groups did not differ in terms of age or gender. The patients in Group 2 received more chemotherapy lines before post-transplant salvage treatment (median 3, range 1-6) compared to those in historical Group 1 (median 2, range 1-6) (p=0.013). No patient was treated with immune check points inhibitors. The response to salvage treatment in the majority of patients in historical Group 1 was assessed with conventional computer tomography (CT), while in all patients in Group 2 with CT combined with positron emission tomography. Results The rate of the objective response rate defined as the complete or partial response was higher in Group 2 (84% vs 60%, p<0.001). Of a total of 121 patients in Group 1, 34 (28%) proceeded to the second autoHCT, and 27 (22%) to alloHCT, compared to 4 (9%) and 20 (45%) of 44 patients in Group 2, respectively (p=0.004). The median follow-up time of survivors is longer in the historical Group 1 compared to Group 2 (40 months vs 19 months, p <0.001). However, at 2 years after the start of post-transplant salvage treatment, the estimated OS for patients in Group 1 was 55.2 % (95 % CI 45.8-64.3 %) compared to 81.9 % (95 % CI 66.5-91.2 %) for patients treated with BV (p=0.009) (figure). The respective estimated 2-year PFS was 41.2% (95 % CI 32.3-50.8 %) for Group 1 and 56.2% (95 % CI 38.5-72.4 %) for Group 2 (p=0.038). Importantly, the OS of patients who proceeded to alloHCT after BV-based salvage treatment was statistically significantly better compared to patients treated with alloHCT in the historical pre-BV group (2-year OS 81% vs 55%, p< 0.001). Conclusions In the era of brentuximab vedotin, significantly more patients with HL relapsing after autoHCT achieve objective response and proceed to allogeneic HCT. This most likely translates to the better PFS exceeding 24 months and most importantly to the significantly better OS of patients treated with BV compared to those treated with conventional salvage chemotherapy in the pre-BV era. Figure Disclosures Czyz: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dlugosz-Danecka:Roche: Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Macrogenomics: Research Funding; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Jurczak:Gilead: Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Roche: Research Funding; Servier: Research Funding; MorphoSys: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Research Funding; Novo Nordisk: Research Funding; Bayer: Research Funding; Celtrion: Research Funding. Walewski:Gilead: Other: Travel Expenses; Bristol-Myers Squibb: Consultancy, 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, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding; Amgen: Consultancy, 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; Servier: Honoraria; Takeda: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wrobel:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Zaucha:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Significance of Degree of HLA Disparity When Using Haploidentical Donors with T-Replete PBSC and Post-Transplantation Cyclophosphamide (PTCy) in Acute Myeloid Leukemia (AML) in First Complete Hematologic Remission (CR1)

Blood ◽

10.1182/blood-2021-149651 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3910-3910

Author(s):

Mohamed A. Kharfan-Dabaja ◽

Myriam Labopin ◽

Ernesto Ayala ◽

Ali Bazarbachi ◽

Didier Blaise ◽

...

Keyword(s):

Board Of Directors ◽

Cumulative Incidence ◽

Research Funding ◽

Acute Gvhd ◽

Chronic Gvhd ◽

Hazard Ratio ◽

Advisory Committees ◽

Group 2 ◽

Hla Mismatches ◽

Group 1

Abstract Background: Haploidentical allogeneic hematopoietic cell transplantation (haplo) has expanded applicability of the procedure to patients for whom a suitable HLA compatible donor was not available in the past. A small multicenter retrospective study of 185 patients with hematologic malignancies who received a nonmyeloablative preparative regimen followed by infusion of bone marrow (BM) hematopoietic cells from haploidentical donors showed no significant association between the number of HLA mismatches (HLA-A, -B, -C, and -DRB1 combined) and risk of acute grade 2-4 graft-versus-host disease (GVHD) (hazard ratio [HR]=0.89; P=0.68 for 3-4 mismatches vs fewer antigen mismatches). This haploidentical transplant platform has certainly evolved. Nowadays, G-CSF mobilized peripheral blood stem cells (PBSC) are commonly used owing to its increased convenience vis-à-vis performing a BM harvest. Study population: Here, we evaluate post transplant outcomes when using haploidentical donors with T-replete PBSC and PTCy in AML in CR1. A total of 494 patients (4/8 HLA mismatch (group 1)=360, 2-3/8 HLA mismatch (group 2)=134) underwent the procedure at an EBMT participating center. The primary endpoints were cumulative incidences of grade 2-4 acute GVHD and chronic (all grades) GVHD. Secondary endpoints included cumulative incidence of relapse (RI), non-relapse mortality (NRM), leukemia-free (LFS) and overall survival (OS) and GVHD-free relapse-free survival (GRFS). Results: Group 1 and group 2 were not statistically different in regards to median age at allografting (54.1 vs. 56.1 years, p=0.51), median year of haplo transplantation (2018 vs. 2018, p=0.36), incidence of de novo AML (86.4% vs. 88.1%, p=0.63), Karnofsky equal or more than 90 (77.5% vs. 79.1%, p=0.70), and use of myeloablative conditioning (MAC) (44.7% vs. 48.5%, p=0.45). Patients in group 1 had a longer time from diagnosis to haplo-transplantation (5.3 vs. 4.9 months, p=0.03). In multivariate analysis, group 1 and group 2 did not differ in cumulative incidence of grade 2-4 acute GVHD (Hazard ratio (HR)=0.89 (95%CI=0.62-1.26), p=0.51) but group 1 had a significantly higher incidence of chronic (all grades) GVHD (HR=1.49 (95%CI=1.02-2.16), p=0.04). There was no difference in RI (HR=0.73 (95%CI=0.47-1.14), p=0.17), NRM (HR=1.25 (95%CI=0.78-2.02), p=0.36), LFS (HR=0.95 (95%CI=0.69-1.31), p=0.76), OS (HR=1.09 (95%CI=0.76-1.55), p=0.64) and GRFS (HR=1.07 (95%CI=0.81-1.42), p=0.64) between the groups. Presence of adverse cytogenetics was independently associated with higher RI (HR=1.90 (95%CI=1.20-2.99), p=0.006), inferior LFS (HR=1.59 (95%CI=1.15-2.19), p=0.005), inferior OS (HR=1.48 (95%CI=1.05-2.08), p=0.03), and worse GRFS (HR=1.54 (95%CI=1.17-2.04), p=0.002). Conclusion: Results show that patients undergoing haplo-transplantation with 4/8 (vs. 2-3/8) HLA mismatches have a higher incidence of chronic GVHD (all grades) without adversely affecting acute grade 2-4 GVHD, RI, LFS, OS and GRFS. Disclosures Labopin: Jazz Pharmaceuticals: Honoraria. Bazarbachi: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hikma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees. Blaise: Jazz Pharmaceuticals: Honoraria. McDonald: BioCryst Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees. Forcade: Novartis: Other: travel grant. Ciceri: IRCCS Ospedale San Raffaele: Current Employment. Mohty: Takeda: Honoraria; Astellas: Honoraria; Adaptive Biotechnologies: Honoraria; Novartis: Honoraria; Celgene: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria; Sanofi: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Jazz: Honoraria, Research Funding; Pfizer: Honoraria; Amgen: Honoraria.

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Outcome of Third Salvage Autologous Stem Cell Transplantation in Multiple Myeloma

Blood ◽

10.1182/blood.v128.22.993.993 ◽

2016 ◽

Vol 128 (22) ◽

pp. 993-993 ◽

Cited By ~ 1

Author(s):

Laurent Garderet ◽

Simona Iacobelli ◽

Anja van Biezen ◽

Linda Koster ◽

Peter Dreger ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Board Of Directors ◽

Research Funding ◽

Conditioning Regimen ◽

New Drugs ◽

Advisory Committees ◽

The Third ◽

First Relapse ◽

Time To Relapse

Abstract Background. Autologous stem cell transplantation (ASCT) remains a gold standard treatment for younger patients with multiple myeloma (MM). With the aid of new drugs, the patients live longer and third salvage ASCT is an increasingly used option. However, the outcome of third salvage ASCT has not yet been analyzed. Methods. Between 1997 and 2010, 1288 MM patients who had received at least 3 ASCT were registered in the EBMT database. We excluded patients older than 75 years, those with a time from diagnosis to first ASCT of more than 10 years, patients transplanted with bone marrow, those with a time between relapse and ASCT of less than one month and those with an uncertain relapse date. Planned tandem ASCT was considered to be performed within a 6 month interval and at least 1 month apart. The conditioning regimen for the third transplant was high dosemelphalan alone or in combination withbusulfan orbortezomib. We could distinguish two main groups: 417 patients who received tandem ASCT and then a third ASCT after single relapse (AARA group) and 72 patients who received one ASCT, a second ASCT after first relapse, and a third ASCT after second relapse (ARARA group). A third group, who received tandem ASCT after relapsing following single ASCT comprised only 25 patients and was not studied. Results. We compared the two groups AARA vs ARARA. A third ASCT was performed in the AARA group in more recent years (p=0.047). There were more males than females (65% vs 72%) in both groups (p=NS). The main myeloma isotype was IgG (56% vs 58%). The ISS stage at diagnosis was similar (stage III in 70% vs 72% of cases). The time interval between diagnosis and first ASCT tended to be shorter in the AARA group (p=0.089), being within the first 6 months in 50% vs 38% of patients. The status at third ASCT was different: CR, 5% vs 4%: VGPR or PR, 45% vs 19%: MR or stable disease, 12% vs 15%: primary refractory/progressive disease, 38% vs 62% (p<0.001). A Karnofsky score of >70% at third ASCT was reported in 91% vs 90% of cases. The conditioning regimen at third ASCT was different between the two groups: melphalan 200 mg/m2, 42% vs 18%: melphalan 140 mg/m2, 6%vs 12%: other 52%vs 70% (p=0.018). The median age at third ASCT was 59vs 61 years. There was a trend to a longer time between first ASCT and first relapse (27vs 22 months (p=0.056)) in the AARA group while the interval between first ASCT and third ASCT was much shorter (44vs 64 months (p<0.001)). The time between the last relapse and third ASCT was similar (9vs 11 months (p=0.4)). The median follow-up was similar (70vs73 months (p=0.9)). Engraftment was similar (96%vs93% (p=0.35)).The best response achieved after the third ASCT was superior in the AARA group: CR, 32%vs12%: VGPR or PR, 60%vs71% :MRor SD, 4%vs14%: progression, 4%vs3% (p<0.001). The median OS after third ASCT was much higher in the AARA group: 30vs19 months (p=0.01) (Figure 1). The causes of death were: relapse/progression, 84%vs84%: second primary malignancies (SPM), 0.4%vs3.6%: other, 16%vs13%. There was a trend to more SPM including both hematologic and solid tumors in the ARARA group (p=0.068) with a shorter median time to SPM, 12vs42 months (p=0.004). Focusing on the AARA group, the longer the time from tandem ASCT to first relapse, the better the OS after the third transplant: if relapse occurred within 12 months of tandem ASCT, median OS of 13 months: within 18-24 months, OS of 29 months: within 36-60 months, OS of 59 months (Figure 2). Conclusions.A third ASCT is feasible in MM with more than 80% of patients achieving at least PR although with increased non relapse mortality. This treatment is mostly used in one of two scenarios: tandem ASCT followed by relapse and a third ASCT, or less commonly a first ASCT followed by a first relapse, a second ASCT, a second relapse and subsequently a third ASCT. The first scenario gives much better results, partly due to a better remission status at the third ASCT with no sign of increased SPM. In this AARA group, if relapse occurred more than 3 years after the initial tandem ASCT, the median OS after third ASCT was more than 4 years. These results should be compared with those obtained with the new drugs, especially in combination. Figure 1. AARAvsARARA groups: Overall Survival after the third transplant Figure 1. AARAvsARARA groups: Overall Survival after the third transplant Figure 2. AARA group: Overall Survival after the third transplant according to the time to relapse following tandem ASCT. Figure 2. AARA group: Overall Survival after the third transplant according to the time to relapse following tandem ASCT. Disclosures Garderet: Takeda: Consultancy; Amgen: Consultancy; BMS: Consultancy, Honoraria; Novartis: Consultancy. Dreger:Janssen: Consultancy; Gilead: Speakers Bureau; Novartis: Speakers Bureau; Novartis: Consultancy; Gilead: Consultancy; Roche: Consultancy. Leleu:TEVA: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; LeoPharma: Honoraria; Pierre Fabre: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria. Peschel:MophoSys: Honoraria. Meuleman:Bristol-Myers-Squibb: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Takeda: Consultancy. Ciceri:MolMed SpA: Consultancy. Schönland:Janssen, Prothena, GSK: Consultancy, Employment, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommations, Patents & Royalties, Research Funding, Speakers Bureau. Kröger:Sanofi: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; Novartis: Honoraria, Research Funding.

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Patient's Preference for Making Informed Treatment Decisions Confidently: Results from a Large Multiple Myeloma Patient Survey across 12 Countries in Europe and Israel

Blood ◽

10.1182/blood-2020-142532 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 23-23

Author(s):

Alessandra Brescianini ◽

Renaud Desgraz ◽

Ananda Plate ◽

Kathryn E. Morgan ◽

Ana Vallejo ◽

...

Keyword(s):

Decision Making ◽

Multiple Myeloma ◽

Board Of Directors ◽

Research Funding ◽

Treatment Effectiveness ◽

Treatment Decision ◽

Publicly Traded ◽

Advisory Committees ◽

Informed Treatment ◽

Types Of Information

Background: Patient (pt) involvement in treatment decisions or 'shared decision making' has been associated with increased pt satisfaction, increased compliance to advice from health professionals, enhanced treatment adherence and overall improved treatment outcomes. Methods: A multinational non-interventional cross-sectional survey was designed and aimed to enrol approximately 1,000 adult pts with multiple myeloma (MM) through Myeloma Patients Europe's (MPE) member network across 12 participating countries: France, Israel, Netherlands, United Kingdom (UK), Sweden, Germany, Hungary, Austria, Finland, Switzerland, Poland and Romania. Patient advocacy organizations were asked to disseminate a URL link for the survey to pts by posting the link on their website, e-mailing the link to pt members on their mailing list or through social media. The primary survey objective was to describe pt confidence in making an informed treatment decision. Main secondary objectives were to describe how pt confidence in making an informed treatment decision was associated with types of information, importance of information and sources of information. Pts fulfilling the following criteria were included: adults who had started MM treatment and received at least one dose, who were able to self-report diagnosis of MM and recall the decision-making process at the start of their most recent line of treatment, and who were able and willing to complete an online questionnaire lasting approximately 30 minutes. Results: Out of 4325 pts who accessed the online survey link, 1559 pts fulfilled eligibility criteria and were included in the primary analysis, of which 1081 provided fully completed surveys. France, Israel, Netherlands, and UK were the largest recruiters with over 200 pts each. Median age of respondents was 54-64 years. Time since diagnosis was 0-4 years for over half of pts (53.1%), and ≥16 years since diagnosis for 4.8% of pts. The majority of pts had received 1 line (40.1%, n=592) of anti-MM treatment, 20.5% (n=303) of pts had received 2 lines, 16.0% (n=236) of pts had received 3 lines, and 19.9% (n=294) reported having received 4 or more lines of treatment. Last treatment decision was taken <3 months before the survey for 26.1% of respondents, and >2 years ago for another 25.5% of respondents. Of the 1112 pts who responded to the question for the primary objective, half of pts (54.4%, n=605) reported being very confident in their most recent treatment decision, and 37.2% (n=414) of pts reported being somewhat confident. Similarly, over half of pts (56.8%, n=634/1116) felt that they were 'very involved' in their last treatment decision, 28.4% (n=317/1116) reported being 'somewhat involved'. Confidence in making an informed treatment decision did not appear to differ by lines of therapy, primary treating physician, type of clinic primarily treated at, or whether help from a carer was received. In terms of types of information received, pts most commonly received information on location of treatment (84.5%, n=1037), mode of administration (83.0%, n=1019), frequency of treatment (77.7%, n=953) and common side effects (72.2%, n=886), and least commonly received information on overall survival (OS) benefit (38.4%, n=471) and how long until MM returns (30.9%,n=379) or healthcare provider costs (20.0%, n=245). Information relating to treatment effectiveness (OS benefit, likelihood treatment would work, how long until MM returns) were reported as the most important types of information amongst those who received them, followed by types relating to treatment tolerability (how safe the treatment is). Operational aspects of treatment (mode of administration, location of treatment and healthcare provider costs) were considered the least important type of information. Receiving the types of information perceived as most important by pts was significantly associated with increased pt confidence in making an informed treatment decision. Conclusion: The most important types of information to pts with MM are related to treatment effectiveness and tolerability. However, effectiveness seems to be communicated to pts less frequently than tolerability and this may be due to the uncertainty surrounding this type of information. However, the survey results suggest some elements on effectiveness should be considered to be shared with pts to increase their confidence in making an informed treatment decision. Disclosures Brescianini: Amgen: Current Employment, Current equity holder in publicly-traded company. Desgraz:Amgen: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Plate:Pfizer: Research Funding, Speakers Bureau; Roche: Research Funding, Speakers Bureau; Sanofi: Research Funding, Speakers Bureau; Takeda: Research Funding, Speakers Bureau; ASCO: Membership on an entity's Board of Directors or advisory committees; ESMO: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding, Speakers Bureau; Amgen: Research Funding, Speakers Bureau; Myeloma Patients Europe: Current Employment; Novartis: Research Funding, Speakers Bureau; Mundipharma: Research Funding, Speakers Bureau; Karyopharm: Research Funding, Speakers Bureau; Janssen: Research Funding, Speakers Bureau; GSK: Research Funding, Speakers Bureau; Oncopeptides: Research Funding, Speakers Bureau. Morgan:Amgen, BMS, GSK, Janssen, Karyopharm, MundiPharma, Novartis, Oncopeptides, Pfizer, Roche, Sanofi, Takeda: Research Funding, Speakers Bureau; Myeloma Patients Europe: Current Employment. Vallejo:Amgen, BMS, GSK, Janssen, Karyopharm, MundiPharma, Novartis, Oncopeptides, Pfizer, Roche, Sanofi, Takeda: Research Funding; Myeloma Patients Europe: Current Employment. Wetten:Amgen: Current Employment, Current equity holder in publicly-traded company. DeCosta:Amgen Ltd: Current Employment, Current equity holder in publicly-traded company. Suzan:Amgen: Current Employment, Current equity holder in publicly-traded company.

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Preliminary Results Of A Mass Spectrometry Based Bottom Up Proteomic Approach On Bone Marrow Plasma Cells From Patients With Multiple Myeloma (MM)

Blood ◽

10.1182/blood.v122.21.1887.1887 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1887-1887

Author(s):

Beycan Ayhan ◽

Duygu Ozer Demiralp ◽

Klara Dalva ◽

Meral Beksac

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Plasma Cell ◽

Plasma Cells ◽

B Cell Lymphoma ◽

Ionization Mass ◽

Advisory Committees ◽

Group 3 ◽

Group 2 ◽

Group 1

Abstract Aim The molecular mechanisms responsible from evolution to malignant monoclonal plasmacytosis is still under investigation. The aim of this prospective study was to analyze the proteomics profile of plasma cells obtained from MGUS, SMM and symptomatic myeloma patients to be able to investigate the differences at protein level between patients with low vs high plasma cell content (PCC). Material and Methods Marrow samples were collected from 30 patients newly diagnosed with Multiple Myeloma (n: 28 symptomatic and n: 1 smoldering (SMM)) and n:1 MGUS) at Ankara University Department of Hematology. Plasma cells were isolated by CD138+ selection before protein extraction. The patients were classified mainly in to three groups according to marrow PCC by flow cytometry: group1: 0-9, group 2: 10-20 and group 3: >20 %. The protein profiles of these three groups were constructed and compared via 2D gel electrophoresis by using PDQuest 8.01 analysis. Up/down regulated protein spots were identified with Matrix-assisted laser desorption/ionization mass spectroscopy(MALDI) by Peptide Mass Fingerprinting (PMF) analysis Results All protein spots that were detected according to PCC with PDQuest analysis are as follows: 135 spots in group 1 142 spots in group 2 and 145 spots in group 3 Among these spots, 27 spots with significant expression density difference (at least 2-fold) were detected between group 1 and 2, 36 spots between group 1 and group 3 and 28 spots between group 2 and group 3. 36 of these protein spots were were used in peptide isolation by using trypsin. PMF analyses were carried out in MALDI-TOF mass spectrometer. From these spots, eight proteins were identified by using Mascot: Endoplasmin (ERp99), Calreticulin(ERp60), MZB1(Marginal zone B and B1 cell specific protein/pERp1), Actin cytoplasmic1(ACTB), Myeloblastin (Leukocyte proteinase 3), Thioredoxin domain-containing protein 5 (TXNDC5/ERp46), Apoptosis regulator B-cell lymphoma 2 (Bcl-2) and Peroxiredoxin-4 ( Table 1, Figure 1). The remaining 28 spots are under investigation. In group 3 the density of protein spots which contain Calreticulin, MZB1, Myeloblastin and TXCDN5 increased, and which contain Actin and Endoplasmin decreased significantly (Table 1). There was a negative corelation between the Peroxiredoxin expression level and the PCC which resulted in disappearance as the percentage of PCC increased. Moreover, not only Peroxiredoxin, but also BCL-2 protein was detected only in the group with PCC >20 %. To avoid the changes that can be attributable to PC counts equal amounts of protein were analyzed from each group. Conclusion Until now there is only one published study utilizing proteomics in MM and reports 268 proteins (Chun Hua Lu et al, J Proteomics Informatics 2010). Ours is the first proteomics study comparing plasma cell proteins with PCC. The functional properties of these proteins are summarized (Table 2). High protein production and folding plus Ca changes in MM support our findings on chaperons and Ca binding protein changes. Out of these eight proteins only bcl-2, MZB1 and calreticulin were previously reported to be involved in the biology of MM. Disclosures: Beksac: 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; Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees.

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