Overview of French Routine Clinical Practice for the Management of Chemotherapy-Induced Anemia (CIA) with Biosimilar Epoetin Alfa in 563 Patients with Lymphoid Malignancies: A National Observational Study (The OncoBOS study)

Abstract Background. OncoBOS is a prospective, non-interventional study conducted in France to describe modalities of treatment with Binocrit® in routine clinical practice setting, for the correction of hemoglobin (Hb) in patients with CIA receiving chemotherapy (CT) for solid tumors, lymphoma or myeloma. This analysis focuses on patients with lymphoid malignancies (LM). Patients & methods. Patient ≥18 years old with LM, CIA and eligible for treatment with Binocrit® were included. This analysis reports patients characteristics along with anemia-related data such as Hb outcomes, Binocrit® treatment characteristics and concomitant treatments received, at baseline, 3-4 weeks and 12 (± 1) weeks later. Factors associated with a Hb increase ≥2 g/dL in patients with LM were analyzed by means of univariate and multivariate analyses. Results. 563 evaluable patients (302 males (53.6%), mean age 67.9 (SD 14.0) years were recruited from 34 sites, between September 2011 and July 2014. Non-Hodgkin lymphoma (NHL) (281 patients; 49.9%) and multiple myeloma (165 patients; 29.3%) were most prevalent. Among patients with NHL, 46.0% had a diffuse large B cell lymphoma, 11.5% a follicular lymphoma and 11.1% a mantle cell lymphoma. 62.5% of patients with NHL had a stage IV disease and bone marrow was involved by NHL in 45.2% of patients. A vast majority of patients (84.3%) suffering from multiple myeloma had a Durie-Salmon stage III myeloma. Mean baseline Hb was 9.5 (SD 1.0) g/dL, which increased by an average of 0.9 (SD 1.4) g/dL and 1.9 (SD 1.7) g/dL after 1 and 3 months, respectively. A Hb increase ≥1 g/dL was achieved by 51.3% of patients after 3-4 weeks of treatment with Binocrit®. About half of patients (53.0%) achieved a Hb increase ≥2 g/dL at week 12 (± 1). Patients received a mean Binocrit® dose of 31252.4 ± (SD 5815.9; median: 30000) UI once-weekly, over an average time span of 10.8 (SD 3.2; median: 13) weeks. Iron status (serum ferritin and transferrin saturation coefficient) was assessed in 29.1% of subjects at baseline. In total, 2.8% and 1.4% of patients concomitantly received oral or intravenous iron, respectively, during the follow-up period. 12.1% and 11.6% of patients received a folate supplementation at week 3-4 and 12, respectively. Moreover, 16.2% and 15.0% of patients received red blood cells transfusion over the 3-4 first weeks, and over the next 2 months, respectively. Over the treatment period, no treatment‐related adverse reaction was recorded. Factors negatively/positively associated with a Hb increase ≥2 g/dL (p<0.05) in the multivariate analysis were: prior radiotherapy [HR 0.16 (CI95% 0.04;0.64)]; history of venous thrombotic disease [HR 1.93 (1.14;3.28)]; administration of folate during the follow-up [HR 2.43 (1.69;3.49)]; a Hb level < 8 or [8;10[ g/dL at inclusion [HR 3.04 (1.97;4.69) and HR 1.62 (1.25;2.11), respectively]; 2 units of red blood cells received over the treatment period [HR 2.82 (1.91;4.16)]. Conclusions. This study indicates that in real-life clinical conditions Binocrit® increases effectively Hb, without any adverse drug reaction, in anemic patients with lymphoid malignancies, whatever chemotherapy received. The effect of treatment with Binocrit® is rapid, with mean hemoglobin increase of 0.9 (SD1.4) g/dL seen as early as 3 or 4 weeks following the start of therapy. Disclosures Karlin: Janssen: Honoraria; BMS: Honoraria; Amgen: Honoraria; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria. Metges:Sandoz: Consultancy. Khobta:Sandoz: Membership on an entity's Board of Directors or advisory committees. Boschetti:Sandoz: Membership on an entity's Board of Directors or advisory committees. Toledano:Sandoz: Membership on an entity's Board of Directors or advisory committees. Aubron-Olivier:Sandoz: Employment. Fernet:Sandoz: Employment. Fitoussi:Sandoz: Membership on an entity's Board of Directors or advisory committees.

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Four-Year Interim Analysis of Miroir, a French Multicenter, Non-Interventional Study of Pomalidomide in Relapsed/Refractory Multiple Myeloma

Blood ◽

10.1182/blood-2019-124484 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1836-1836

Author(s):

Olivier Decaux ◽

Margaret Macro ◽

Sophie Gourgou ◽

Florence Lachenal ◽

Caroline Bureau Lenoir ◽

...

Keyword(s):

Multiple Myeloma ◽

Clinical Practice ◽

Board Of Directors ◽

Interim Analysis ◽

Research Funding ◽

Routine Clinical Practice ◽

Interventional Study ◽

Real World Data ◽

Advisory Committees ◽

Refractory Multiple Myeloma

BACKGROUND Real-world data on the use of pomalidomide (POM) for the treatment (Tx) of relapsed/refractory multiple myeloma (RRMM) are limited. The MIROIR study was designed to evaluate POM Tx in routine clinical practice in France. Here, we present results from a prespecified 4-year interim analysis. METHODS MIROIR is a multicenter, observational, ambispective, non-interventional study of POM in routine clinical practice. Adult patients (pts) with MM who initiated POM Tx in France between October 1, 2014, and September 30, 2018, were included. All pts were required to be enrolled in the French IMNOVID® registry. Data were collected from medical records of consenting pts. Key exclusion criteria included previous treatment with POM or simultaneous participation in a clinical trial. The primary endpoint is progression-free survival (PFS) at 6 months. Key secondary endpoints include time to next Tx (TTNT), overall survival (OS), and safety. This study is ongoing; targeted enrollment is 3000 pts (ClinicalTrials.gov, NCT02902900). RESULTS A total of 2099 pts were included in this analysis (median follow-up: 23.3 months; data cutoff: February 1, 2019). Median age was 70.0 years, and 655 pts (31.2%) were aged ≥ 75 years; 1134 pts (54.0%) were male. Median time from start of first-line Tx to POM initiation was 51.4 months. Pts had received a median of 3 prior lines of therapy (range: 0-9), with 914 (43.5%), 644 (30.7%), 312 (14.9%) and 229 pts (10.9%) receiving ≤ 2, 3, 4, and ≥ 5 prior lines, respectively. From 2014 to 2016, the median number of prior lines of therapy before POM initiation was 3, and from 2016 to 2018, the median was 2. Nearly all pts received prior lenalidomide (LEN; 97.0%) and bortezomib (96.7%). POM was initiated at 4 mg/day in 1635 pts (77.9%) overall and in 1216 pts (84.2%) aged < 75 years and in 419 pts (64.0%) aged ≥ 75 years. Dexamethasone was prescribed at 20 mg/day and 40 mg/day in 507 (35.1%) and 732 pts (50.7%) aged < 75 years and in 405 (61.8%) and 62 pts (9.5%) aged ≥ 75 years. Overall, the 6-month PFS rate was 51.7% (95% CI, 49.4%-54.1%). Other key PFS data in pt subgroups are reported in the Table. In the overall population, median TTNT, 12-month OS rate, and median OS were 10.4 months (95% CI, 9.7-11.2), 70.6% (95% CI, 68.5-72.6), and 24.6 months (95% CI, 22.9-not reached), respectively. Among 1164 pts (55.5%) with ≥ 1 adverse event (AE), the most common AEs were neutropenia (290 pts; 24.9%), infections (263 pts; 22.6%), thrombocytopenia (99 pts; 8.5%), and asthenia (87 pts; 7.5%). POM dose was reduced due to an AE in 20.7% of pts; POM Tx was interrupted or discontinued due to an AE in 36.2% and 15.2% of pts, respectively. CONCLUSIONS The results of this interim analysis confirm the efficacy of POM reported in clinical trials and underscore its role in Tx of RRMM, including after LEN Tx. Median PFS in pts with ≤ 2 prior Tx lines was numerically longer than in pts who had more Tx lines, supporting earlier Tx with POM. PFS outcomes were similar regardless of the duration of LEN Tx (< or ≥ 6 months) before initiation of POM and whether pts had received LEN or another Tx as their most recent therapy. The latter finding suggests that POM can be used after relapse or resistance to LEN and that there is no need to replace an IMiD agent with another class of treatment. Disclosures Decaux: Celgene Corporation, Janssen, Takeda, Amgen: Honoraria. Macro:Celgene, Janssen, Amgen, Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Financial Support. Gourgou:Celgene: Employment, Equity Ownership. Lachenal:Celgene: Other: Scientific Comittee's. Stoppa:Celgene: Honoraria. Jaccard:Abbvie: Honoraria; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Pfizer: Honoraria. Moreau:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Perrot:jannsen: Honoraria, Membership on an entity's Board of Directors or advisory committees; takeda: Honoraria; Amgen: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding. Karlin:AMGEN: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fohrer:Celgene: Consultancy, Honoraria. Leleu:Carsgen: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Merck: Honoraria; Oncopeptide: Honoraria; Karyopharm: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Hulin:celgene: Consultancy, Honoraria; Janssen, AbbVie, Celgene, Amgen: Honoraria.

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Clinical & Economic Implications of Hydroxyurea Intolerance in Polycythemia Vera in Routine Clinical Practice in Israel

Blood ◽

10.1182/blood-2020-141821 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 23-24

Author(s):

Martin H. Ellis ◽

Tamar Tadmor ◽

Gabriel Chodick ◽

Naama Yekutiel ◽

Moti Levi ◽

...

Keyword(s):

Clinical Practice ◽

Polycythemia Vera ◽

Board Of Directors ◽

Routine Clinical Practice ◽

Institutional Research ◽

Advisory Committees ◽

Economic Implications ◽

A Company ◽

Research Grant

Background: Hydroxyurea (HU) is an effective and common therapy for high-risk Polycythemia Vera (PV). Some patients may demonstrate resistance or intolerance to HU, but the consequences of these warrant further studies. Objective: Evaluate the clinical and economic implications of HU resistance/intolerance, in routine clinical practice in Israel. Methods: A retrospective analysis of Maccabi Health Services' (MHS) database was performed. MHS is a Non-for-Profit healthcare insurer and provider in Israel, with over 2.2 million members. Patients were included in the study if they had a recorded PV diagnosis or complete blood count indicative of PV, and had purchased HU for at least 3 months between 2000-2015. Enrolled patients were divided into 3 groups: A) Resistant to HU (patients prescribed 2g/day of HU); B) Intolerant of HU (patients who stopped HU, transitioned to another line of therapy or who developed HU related cytopenias); C) Stable on HU. A mid-time point was added to "Stable" to compensate for the time required for transition in the "Intolerant" group. Only patients who developed Intolerance within 5 years were included. Collected data pertained to demographics, clinical outcomes, resource utilization and expenditure data. Results: A total of 830 patients were identified. Only 3 met criteria for Resistance and were disregarded for further analysis, while 318 (38%) were defined as "Intolerant" and 509 (61%) as "Stable". At baseline, there were no significant differences between "Intolerant" and "Stable" groups, apart from platelet counts (431 vs. 495, respectively) and red cell distribution width (RDW) (18.4 vs. 17.6, respectively). Intolerance was determined based on HU-related cytopenias (n=144, 45% of Intolerant), transition to other treatment line (n=52, 16%) or stopping HU (n=122, 38%). These results indicate some patients continue HU treatment despite lack of disease control. "Intolerant" patients who had transitioned by 5 years from first HU purchase (N=173) and "Stable" patients who met the mid-point of time to transition (N=487) were eligible for comparison. Median follow up time was 4.9 and 5.5 years for "Intolerant" and "Stable" groups, respectively. Thrombotic events occurred in 8% of the "Intolerant" group compared with 3% of "Stable" (p=0.003) and event rate per 100 patient-years was 1.6 versus 0.5 (p<0.001). Progression to MF occurred in 28% versus 5% (p<0.001), and progression to AML occurred in 6% compared with 1% (p<0.001) among "Intolerant" and "Stable", respectively. Interestingly no significant difference was found regarding major arterial thrombotic complications, (myocardial infarction, acute coronary syndrome, cerebrovascular accident or limb ischemia). During study follow up, hospitalization occurred in 84% versus 69% (p<0.001), and hospitalization days were 5.3 vs 1.9 per year (p=0.004) among "Intolerant" and "Stable" groups, respectively. Death occurred in 58% of "Intolerant" compared with 30% of "Stable"(p<0.001). Treatment costs for an Intolerant patient in the first year after intolerance were 2.6-fold higher than those for a Stable patient, driven mainly by hospitalization costs being 3.6-fold higher (data available from 2010). Conclusions: The results of this analysis indicate that intolerance to HU treatment in PV patients is associated with serious clinical and economic implications, indicating a need for improved treatment for these patients. Disclosures Ellis: Novartis Pharma AG: Consultancy, Honoraria, Other: Institutional research grant; BMS: Consultancy, Other: Institutional research grant; Gilead: Other: Institutional research grant. Tadmor:AbbVie: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Medison: Consultancy, Speakers Bureau; Neopharm: Consultancy, Speakers Bureau; 6. Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Consultancy, Speakers Bureau. Chodick:Novartis Pharma AG: Other: Institutional grant. Yekutiel:Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Other: Institutional grant. Sharf:Novartis Pharma AG: Consultancy, Other: Institutional Grant; Leukaemia Patient Advocates Foundation: Ended employment in the past 24 months, Membership on an entity's Board of Directors or advisory committees; Israeli CML Patient Organisation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Other: Institutional grant; AbbVie: Consultancy, Other: Institutional Grant; Amgen: Consultancy, Other: Institutional grant; Bristol Mayers Squibb: Consultancy, Other: Institutional Grant; Celgene: Consultancy, Other: Institutional Grant; AOP Orphan: Other: Institutional grant; CTI: Other: Institutional grant; Medison: Other; Roche: Other; Jansseb: Other; Pfizer: Consultancy, Other; Takeda: Other; Gilead: Other. Feine:Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Current Employment. Leef:Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Current Employment. Ben Zvi:Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Current Employment. Shavit:6. Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Current Employment.

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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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Radioimmunotherapy for Mantle Cell Lymphoma: 5-Year Follow-up of 90 Patients from the International RIT-Registry

Blood ◽

10.1182/blood-2019-124192 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5263-5263

Author(s):

Karin Hohloch ◽

Christine Windemuth-Kieselbach ◽

Pier Luigi Zinzani ◽

Roberto E. Cacchione ◽

Wojciech Jurczak ◽

...

Keyword(s):

Follicular Lymphoma ◽

Mantle Cell Lymphoma ◽

Board Of Directors ◽

Research Funding ◽

Cell Lymphoma ◽

Primary Therapy ◽

First Line ◽

Advisory Committees ◽

Mantle Cell

To assess the efficacy of radioimmunotherapy (RIT) with 90yttrium-ibrutinib-tiuxetan (90Y-IT) in mantle cell lymphoma, data from 90 patients registered in the RIT Network with a median follow-up (FU) of 5.5 years after RIT were evaluated. 90Y-IT was given as first-line therapy in 45 (50%) (consolidation 44 pts., primary therapy 1 pt.) and at relapse in 45 (50%) patients (consolidation 24 pts., recurrence 12 pts., therapy refractory 3 pts., conditioning 2 pts., other 4 pts.). As a first-line treatment, 30 patients (pts.) (67%) achieved CR, 10 pts. (22%) PR%., 1 pt. (2%) PD, and for 4 pts. (9%) no response data was available. At relapse, CR was achieved in 17 pts. (38%), PR in 6 pts. (13%), SD in 2 pts. (4%), and 6 pts. (13%) had PD, while the response was not documented for 14 pts. (31%). After a median FU of 5.5 years, median PFS for all patients was 2.11 (95%CI: 1.03-2.32) years, and median OS was 4.05 (95%CI 2.79-7.21) years. Eleven pts. (12.2%) developed second malignancy. In conclusion, this is the largest report of MCL pts. treated with 90Y-IT to date. 90Y-IT was most often used as consolidation after first- and second-line chemotherapy and may improve the results achieved using chemoimmunotherapy alone. However, the results are less encouraging compared to treatment with small molecules such as ibrutinib. Disclosures Zinzani: TG Therapeutics: Honoraria, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy. Jurczak:Sandoz: 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; Roche: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Bayer: Research Funding; Gilead: Research Funding; MorphoSys: Research Funding; Incyte: Research Funding; Novo Nordisk: Research Funding; Servier: Research Funding; TG Therapeutics: Research Funding; Celtrion: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Truemper:Seattle Genetics, Inc.: Research Funding; Takeda: Consultancy, Research Funding; Roche: Research Funding; Nordic Nanovector: Consultancy; Mundipharma: Research Funding; Janssen Oncology: Consultancy. Scholz:Janssen-Cilag: Consultancy; Hexal: Consultancy; Takeda: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Pfizer: Speakers Bureau; Roche: Consultancy; GILEAD: Consultancy, Speakers Bureau; Daiichi Sankio: Consultancy. OffLabel Disclosure: Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin) is approved for treatment of patients with relapsed follicular lymphoma and as consolidation therapy after chemo(immuno)therapy of patients with follicular lymphoma.

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Impact of Interim FDG-PET (iPET) in the Outcomes of Patients with Aggressive B-Cell Lymphomas Receiving DA-EPOCH-R

Blood ◽

10.1182/blood-2019-122393 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2898-2898

Author(s):

Vania Phuoc ◽

Leidy Isenalumhe ◽

Hayder Saeed ◽

Celeste Bello ◽

Bijal Shah ◽

...

Keyword(s):

B Cell ◽

Board Of Directors ◽

Fdg Pet ◽

Research Funding ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Advisory Committees ◽

End Of Treatment

Introduction: 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) remains the standard of care for baseline and end of treatment scans for aggressive non-Hodgkin lymphomas (NHLs). However, the role of interim FDG-PET remains not as well defined across aggressive NHLs, especially in the era of high-intensity chemoimmunotherapy. Interim FDG-PET (iPET) can serve as an early prognostic tool, and prior studies evaluating the utility of iPET-guided treatment strategies primarily focused on diffuse large B-cell lymphomas (DLBCL) and frontline R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Classification criteria systems assessing response also differ between studies with no clear consensus between use of Deauville criteria (DC), International Harmonization Project (IHP), and the ΔSUVmax method. Methods: This study evaluates our institutional experience with iPET during treatment with DA-EPOCH ± R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin with or without Rituximab) in aggressive NHLs. We retrospectively evaluated 70 patients at Moffitt Cancer Center who started on DA-EPOCH ± R between 1/1/2014 to 12/31/2018 for aggressive NHLs. Response on interim and end-of-treatment (EOT) scans were graded per DC, IHP, and ΔSUVmax methods, and progression free survival (PFS) probability estimates were calculated with chi-square testing and Kaplan Meier method. PFS outcomes were compared between interim negative and positive scans based on each scoring method. Outcomes were also compared between groups based on interim versus EOT positive or negative scans. Results: We identified 70 patients with aggressive NHLs who received DA-EPOCH ± R at our institute. The most common diagnoses were DLBCL (61%) followed by Burkitt's lymphoma (10%), primary mediastinal B-cell lymphoma (9%), plasmablastic lymphoma (7%), gray zone lymphoma (6%), primary cutaneous large B-cell lymphoma (1%), primary effusion lymphoma (1%), and other high-grade NHL not otherwise specified (3%). Of the 43 patients with DLBCL, 21/43 (49%) had double hit lymphoma (DHL) while 7/43 (16%) had triple hit lymphoma (THL), and 3/43 (7%) had MYC-rearranged DLBCL while 2/43 (5%) had double expressor DLBCL. Thirty nine out of 70 (56%) were female, and median age at diagnosis was 58.39 years (range 22.99 - 86.86 years). Most patients had stage IV disease (49/70, 70%), and 43/70 (61%) had more than one extranodal site while 45/70 (64%) had IPI score ≥ 3. Forty-six out of 70 (66%) received central nervous system prophylaxis, most with intrathecal chemotherapy (44/70, 63%). Fifty-five out of 70 (79%) had iPET available while 6/70 (9%) had interim computerized tomography (CT) scans. Fifty-six out of 70 (80%) had EOT PET, and 4/70 (6%) had EOT CT scans. Sustained complete remission occurred in 46/70 (66%) after frontline DA-EPOCH ± R (CR1), and 12/70 (17%) were primary refractory while 5/70 (7%) had relapse after CR1. Four of 70 (6%) died before cycle 3, and 3/70 (4%) did not have long-term follow-up due to transition of care elsewhere. Median follow-up was 15.29 months (range 0.85 - 60.09 months). There was significantly better PFS observed if iPET showed DC 1-3 compared to DC 4-5 (Χ2=5.707, p=0.0169), and PFS was better if iPET was negative by IHP criteria (Χ2=4.254, p=0.0392) or ΔSUVmax method (Χ2=6.411, p=0.0113). Comparing iPET to EOT PET, there was significantly better PFS if iPET was negative with EOT PET negative (iPET-/EOT-) compared to iPET positive with EOT negative (iPET+/EOT-), and iPET+/EOT+ and iPET-/EOT+ had worse PFS after iPET-/EOT- and iPET+/EOT- respectively. This pattern in iPET/EOT PFS probability remained consistent when comparing DC (Χ2=30.041, p<0.0001), IHP (Χ2=49.078, p<0.0001), and ΔSUVmax method (Χ2=9.126, p=0.0104). These findings fit clinical expectations with positive EOT scans indicating primary refractory disease. There was no significant difference in PFS when comparing DLBCL versus non-DLBCL (Χ2=3.461, p=0.0628) or DHL/THL versus non-DHL/THL diagnoses (Χ2=2.850, p=0.0914). Conclusion: Our findings indicate a prognostic role of iPET during treatment with DA-EPOCH ± R for aggressive NHLs. Significant differences in PFS were seen when graded by DC, IHP, and ΔSUVmax methods used in prior studies and when comparing interim versus EOT response. Larger studies are needed to confirm these findings. Disclosures Bello: Celgene: Speakers Bureau. Shah:Novartis: Honoraria; AstraZeneca: Honoraria; Spectrum/Astrotech: Honoraria; Adaptive Biotechnologies: Honoraria; Pharmacyclics: Honoraria; Jazz Pharmaceuticals: Research Funding; Incyte: Research Funding; Kite/Gilead: Honoraria; Celgene/Juno: Honoraria. Sokol:EUSA: Consultancy. Chavez:Janssen Pharmaceuticals, Inc.: Speakers Bureau; Genentech: Speakers Bureau; Kite Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

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Primary Pancreatic Lymphoma

Blood ◽

10.1182/blood.v116.21.4150.4150 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4150-4150 ◽

Cited By ~ 1

Author(s):

Elisabeth S. Malin ◽

Christiana E. Toomey ◽

Jill Ono ◽

Aliyah R. Sohani ◽

James S. Michaelson ◽

...

Keyword(s):

Board Of Directors ◽

Hodgkin Lymphoma ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

The Body ◽

Advisory Committees ◽

Not Otherwise Specified ◽

Hodgkin's Lymphomas ◽

Pancreatic Lymphoma

Abstract Abstract 4150 Introduction: Primary extranodal pancreatic non-Hodgkin lymphoma (PPL) makes up no more than 0.16–4.9% of pancreatic malignancies and less than 0.7% of non-Hodgkin's lymphomas (NHL). Since lymphomas involving the pancreas may have a similar clinical presentation to primary pancreatic adenocarcinoma, and often have a similar radiographic appearance, pancreatic lymphoma is often not diagnosed until surgical exploration or definitive surgery for presumed pancreatic cancer. Preoperative distinction of adenocarcinoma and PPL is critical as the management and prognoses of these malignancies are mutually exclusive. The rarity of PPL has made epidemiologic studies difficult to conduct. Methods: We queried our IRB-approved clinicopathologic database, derived from comprehensive tumor registry data at the Massachusetts General Hospital, for all adult patients diagnosed with PPL between 2000 and 2010. The database contains 5821 patients with mature lymphoid malignancies. Cases were included in the analysis if they met clinicopathologic criteria for PPL, defined as dominant disease presentation within the body of the pancreas. Forty-five patients were found to have pancreatic involvement at initial presentation of whom 31 (68.9%) on further investigation had a pancreatic primary and are included in the analysis. For each patient, we collected complete demographic information, clinical presenting features, histology, chemotherapy regimens, use of radiotherapy, and type of surgical biopsy performed. We also collected outcome data including results of interim and final restaging scans. Results: PPL represented 0.5% of all mature lymphomas seen at our institution. The median age at diagnosis was 60 yrs (range 20–91). There were 21 male and 10 female patients. Eighteen patients had Diffuse Large B Cell Lymphoma (DLBCL) (one with a focus of follicular lymphoma (FL) grade 3), two each had Burkitts Lymphoma, FL Grade 1–2, and mantle cell lymphoma (MCL), and one each had small lymphocytic lymphoma (SLL), Hodgkin Lymphoma, Marginal zone lymphoma, and peripheral T cell Lymphoma not otherwise specified. Three patients had NHL not otherwise specified (NOS). Of the 31 patients, 13 patients were stage 4E, 5 were stage 3E, 8 were stage 2E, and 5 were Stage 1E. Seventeen patients presented with jaundice. In 2 cases clinical history at presentation was unavailable. Elevated lactate dehydrogenase (LDH) level was present in 18 of 26 patients (69%) for whom laboratory values were available. B symptoms were present at diagnosis in 13 patients, absent in 17 patients, and unavailable in 1. Diagnosis was made in sixteen patients by fine needle aspiration (FNA), in nine patients by core needle biopsy, in two by incisional biopsies, and four patients were diagnosed after a definitive pancreaticoduodenectomy (Whipple procedure). Information on therapeutic regimen was available for 24 patients. One of these 24 patients was treated with primary radiotherapy without chemotherapy for a grade 1–2 primary pancreatic FL. Twenty-three patients had initial chemotherapy: 8 with R-CHOP, 5 with CHOP, 2 with CVP, and 1 each with CHOP-14, CVP × 1 then CHOP, R-CVP, R-EPOCH, R-CODOX-M/R-IVAC, R-CDOP and R-CP then R-CHOP. One patient was treated with chemotherapy not otherwise specified in the medical record. Four of these 23 patients received consolidative radiotherapy after initial therapy. Chemotherapy had significant efficacy with an overall response rate (ORR) of 75% in all chemotherapy treated patients (10 CR, 8 PR). Therapy information was available on 13 patients with DLBCL with an ORR of 85% (7 CR, 4 PR) to R-CHOP in 8 patients, CHOP in 3, and 1 each R-EPOCH and R-CDOP. One patient died of meningeal relapse of DLBCL despite therapy with R-EPOCH. For the entire PPL group at median follow-up of 28.5 months, the progression free and overall survivals are 48.4% and 64.5%, respectively. At a median follow-up of 33.4 months, the progression free and overall survivals for the DLBCL-PPL group are 50.0% and 66.7%, respectively. Discussion: PPL is a rare extranodal presentation of lymphoma accounting for 0.5% of lymphomas seen at a tertiary referral center. Pre-surgical diagnosis of PPL is critical to avoidance of unnecessary major surgery. The outcome of PPL approximates the outcome of DLBCL in other sites. An increased rate of CNS relapse was not seen with presentations in this extranodal site. Disclosures: Hochberg: Biogen Idec: Speakers Bureau; Genentech: Speakers Bureau; Enzon Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Speakers Bureau; WorldCare: Membership on an entity's Board of Directors or advisory committees; Proventys: Consultancy.

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B Cell Lymphoma In Association with Multiple Myeloma: Analysis of the Biologic Relationship

Blood ◽

10.1182/blood.v118.21.1590.1590 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1590-1590 ◽

Cited By ~ 3

Author(s):

Anuj K. Mahindra ◽

Aliyah R. Sohani ◽

Christiana E. Toomey ◽

James S. Michaelson ◽

Jeffrey A. Barnes ◽

...

Keyword(s):

Multiple Myeloma ◽

B Cell ◽

Board Of Directors ◽

Light Chain ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Prior History ◽

Advisory Committees ◽

Age Of Diagnosis ◽

History Of

Abstract Abstract 1590 Background: The occurrence of a secondary lymphoma in patients with a prior history of B-cell lymphomas has been reported.1, 2 There are few reported occurrences of Multiple Myeloma (MM) in patients (pts) with a prior history of lymphoma and the biologic relationship between the two neoplasms in such cases is unknown. Methods: We queried our IRB approved clinicopathologic database of hematologic malignancies for patients with lymphoma and MM. Of the 4165 pts with B-cell lymphoma and 804 pts with MM, 6 pts with a history of B-cell lymphoma developed MM and 1 patient with a prior history of MM developed a B-cell lymphoma. We describe the morphology, immunophenotype, and clinical features of the 7 pts. The clonal relationship of the 2 components was analyzed using sequencing analysis of immunoglobulin heavy chain variable region (IgVH) genes and by light chain restriction. Results: There were 5 men and 2 women (median age of diagnosis of lymphoma, 65 years; median age of diagnosis of MM, 71 years). The pts with lymphoma included 2 pts with diffuse large B cell lymphoma, 2 pts with small lymphocytic lymphoma, 2 pts with follicular lymphoma and 1 patient with lymphoplasmacytic lymphoma. The development of MM was metachronous in 5 cases, following B-cell lymphoma by 3 years to 23 years and synchronous in 1 case. In 1 patient, the B-cell lymphoma developed 6 years after the diagnosis of MM. 6 pts achieved complete remission after treatment for lymphoma and 1 patient is ongoing treatment. 6 of the 7 pts required treatment for MM soon after diagnosis. 1 patient has smoldering MM and continues to be observed 57 months after diagnosis. FISH analysis indicated IgH rearrangement in 3 pts with MM; 1 patient with 17p deletion and monosomy 13; 3 pts had normal FISH and metaphase cytogenetics. In 3 pts, both neoplasms were kappa light chain restricted; in 1 patient both were lambda restricted; in 1 patient, the lymphoma was lambda light chain restricted while the MM was kappa light chain restricted and the reverse in another pt; in 1 patient the B-cell lymphoma was light chain negative and the MM was kappa restricted. IgVH rearrangement studies in 4 patients in whom tissue samples were available indicated that the two were clonally unrelated in 3 patients and related in only 1 patient. Conclusion: Clonality analysis of rearranged immunoglobulin genes from patients with both B-cell lymphoma and MM provide evidence of separate clonal origins of the two tumors in the majority of cases, thus excluding secondary transformation of the original B-cell clone. The presence or absence of a genetic predisposition to the development of multiple B cell malignancies requires further study.3 Disclosures: Off Label Use: The combination of lenalidomide and everolimue is an off label use in multiple myeloma. Abramson:Genentech: Consultancy; Novartis: Consultancy. Raje:Amgen: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Research Funding; Millenium: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Acetylon: Research Funding.

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Vantage 088: Vorinostat in Combination with Bortezomib in Patients with Relapsed/Refractory Multiple Myeloma: Results of a Global, Randomized Phase 3 Trial

Blood ◽

10.1182/blood.v118.21.811.811 ◽

2011 ◽

Vol 118 (21) ◽

pp. 811-811 ◽

Cited By ~ 8

Author(s):

Meletios Athanasios Dimopoulos ◽

Sundar Jagannath ◽

Sung-Soo Yoon ◽

David S. Siegel ◽

Sagar Lonial ◽

...

Keyword(s):

Multiple Myeloma ◽

New Zealand ◽

Board Of Directors ◽

Histone Deacetylase ◽

Research Funding ◽

Cell Lymphoma ◽

Phase 3 ◽

Advisory Committees ◽

Refractory Multiple Myeloma ◽

Chemotherapy Agents

Abstract Abstract 811 Introduction: Vorinostat (VOR), an oral inhibitor of histone deacetylase class I and class II proteins, regulates genes and proteins involved in tumor growth and survival. The synergistic effects of VOR and bortezomib (BTZ) have been shown in preclinical studies and were confirmed in independent phase 1 trials in patients with relapsed/refractory multiple myeloma (MM), producing objective response rates (ORRs) of up to 42% and overall clinical benefit of up to 90%. Materials and methods: Eligible patients were aged ≥ 18 years, had measurable secretory MM, had received 1 to 3 prior systemic anti-myeloma regimens, and had an Eastern Cooperative Oncology Group status ≤ 2. Previous exposure to BTZ and the presence of extracellular plasmacytoma were allowed per protocol, but patients with prior resistance to BTZ were excluded. Patients were randomized 1:1 to receive 21-day cycles of BTZ (1.3 mg/m2 intravenously; days 1, 4, 8, and 11) in combination with oral VOR 400 mg/d, or matching placebo, on days 1 to 14. Additional use of corticosteroids for the treatment of MM was not allowed during the trial. Patients were treated until disease progression, unacceptable toxicities, or withdrawal from the study. The primary endpoint for this trial was progression-free survival (PFS; occurrence of 412 PFS events). Secondary and exploratory endpoints included ORR (≥ partial response), clinical benefit response (ORR + minimal response), overall survival, time to progression, patient-reported outcomes questionnaires (QLQ-C30, QLQ-MY20), and safety/tolerability of this novel drug combination. Responses and progression were determined according to the European Bone and Marrow Transplantation Group criteria and will be confirmed by an Independent Adjudication Committee. Results: Between January 2009 and January 2011, 637 patients were enrolled from 174 centers in 33 countries across the globe making this trial one of the largest studies conducted in patients with relapsed/refractory myeloma. Median age of the study population was 62 years (range, 29–86 years). Of the enrolled patients, 59% were male and 56% were Caucasian. Patients had received a median of 2 prior regimens (range, 1–3). Prior anti-myeloma agents included BTZ (24%), thalidomide (56%), lenalidomide (13%), melphalan (56%), and stem cell transplantation (35%). As of July 2011, 635 patients had received study medication, with a median exposure of 7 cycles (mean: 7.6 cycles; range 1–30 cycles). Reported median exposure to BTZ monotherapy in previous phase 3 trials was approximately 5 cycles. Conclusions: The study passed the protocol-specified futility analyses by the independent data monitoring committee in November 2010. Database lock is anticipated in November 2011, and top-line data on primary and secondary endpoints will be available at the meeting. Disclosures: Dimopoulos: Celgene, Ortho-Biotech: Consultancy, Honoraria. Off Label Use: Vorinostat, an inhibitor of histone deacetylase, is approved in the US for the treatment of cutaneous manifestations in patients with cutaneous T cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies. Vorinostat is currently under investigation for the treatment of relapsed malignant pleural mesothelioma, relapsed/refractory B cell lymphoma (in combination with other chemotherapy agents), and relapsed/refractory multiple myeloma (in combination with bortezomib and other chemotherapy agents). Jagannath:Merck: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees. Yoon:Celgene: Consultancy; NK Bio: Consultancy. Siegel:Millennium: Honoraria, Research Funding, Speakers Bureau; Merck: Honoraria. Lonial:Millennium: Consultancy; Celgene: Consultancy; Novartis: Consultancy; BMS: Consultancy; Onyx: Consultancy; Merck: Consultancy. Hajek:Celgene: Honoraria; Janssen: Honoraria; Merck: Educational lecture. Facon:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Membership on an entity's Board of Directors or advisory committees. Rosiñol:Celgene: Honoraria; Janssen-Cilag: Honoraria. Blacklock:New Zealand Bone Marrow Donor Registry: Consultancy, Employment; Mercy Hospital, Auckland New Zealand: Consultancy; Leukaemia and Blood Foundation, New Zealand: Consultancy, Membership on an entity's Board of Directors or advisory committees; Middlemore Hospital: Employment, Research Funding. Goldschmidt:Amgen, Novartis, Chugai: Research Funding; Janssen-Cilag, Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Palumbo:Merck: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees. Reece:Merck: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding. Graef:Merck: Employment. Houp:Merck Research Laboratories: Employment. Sun:Merck & Co., Inc.: Employment. Eid:Merck Research Laboratories: Employment. Anderson:Celgene: Consultancy; Millennium: Consultancy; Novartis: Consultancy; BMS: Consultancy; Onyx: Consultancy; Merck: Consultancy; Acetylon: founder.

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Newly Diagnosed Multiple Myeloma (MM) Patients Treated With Lenalidomide Induction and Maintenance Show a Low Incidence Of Second Primary Malignancies (SPMs)

Blood ◽

10.1182/blood.v122.21.2074.2074 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2074-2074

Author(s):

Annamaria Brioli ◽

Charlotte Pawlyn ◽

Walter Gregory ◽

Samantha Hinsley ◽

Samantha Marshall ◽

...

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Incidence Rate ◽

Maintenance Treatment ◽

New Drugs ◽

Newly Diagnosed ◽

Advisory Committees ◽

Non Invasive ◽

To Receive

Abstract Introduction New drugs have significantly improved the outcome of MM patients (pts) increasing both progression free survival (PFS) and overall survival (OS). Among new drugs lenalidomide (LEN) due to its oral availability and favourable toxicity profile is an attractive option both as an induction and as a maintenance treatment, with different studies demonstrating its effectiveness. Long term therapy with LEN, however, has been associated with an increased risk of developing SPMs. Aims We are conducting a large phase III study to evaluate the use of LEN as induction and/or as maintenance therapy. The primary end points of the study are OS and PFS. Secondary end points are response and toxicity. Methods Pts are treated following an intensive or a non intensive pathway based on their eligibility for high dose Melphalan (HDM) and stem cell transplantation (ASCT) and are randomised to receive induction therapy with cyclophosphamide and dexamethasone combined with either LEN (CRD) or thalidomide (CTD). Pts failing to achieve an optimal response are randomised to receive additional therapy with cyclophosphamide, dexamethasone and bortezomib (CVD) or no extra therapy. Pts with minimal or no response will automatically receive further therapy with CVD. A randomisation between LEN maintenance and no maintenance is also performed. Data on the occurrence of SPMs are being routinely collected as part of safety assessment during all protocol phases and follow up. Analyses were performed on treatment actually received. Results As per cut off of the 23rd July, 2371 pts have undergone the induction randomisation, of which 2368 are eligible for the safety analysis; 794 pts entered maintenance randomisation. The median follow up is 1.36 years from initiation of the study and 1.06 years from maintenance randomisation. Localised skin cancer other than melanoma were considered as non-invasive SPMs. At the time of the present analysis 17 SPMs have been reported with a cumulative incidence rate of 0.7% (cumulative rate of 0.6% for invasive SPMs and 0.1% for non-invasive SPMs); four additional patients, reported as having a SPM, were excluded, after central review of the data, either due to a previous history of malignancy or because of the evidence of a pre-existing tumour other than MM at the time of study entry. The median age at the time of SPMs development is 72 years (range 61-92), and the median time from trial entry to development of SPMs is 11 months (range 2.1-27.0). The most common SPMs reported were squamous cell carcinoma (4 pts, 2 invasive and 2 non invasive), breast cancer (3 pts), colon cancer (2 pts) and prostate cancer (2 pts). No haematological SPM has so far been reported. One patient, treated according to the intensive arm with LEN both as induction and maintenance, was reported as having a suspect myelodysplasia (MDS) due to anaemia and thrombocytopenia 2.7 months after entering the maintenance randomisation. No clear histological sign of MDS was found and the values improved after stopping maintenance treatment; these data fit with treatment related toxicity and not with the development of a MDS, and the patient was excluded from this analysis. Ten out of 17 SPMs developed during maintenance treatment or follow up phase, with 7 patients having received LEN maintenance. Median time from maintenance randomisation to SPMs development is 7 months (range 2-20.6 months). The remaining 7 were diagnosed during or immediately after induction. About half of the patients (8/17) were randomised to receive LEN induction; 3 patients received LEN both as induction and as maintenance. Interestingly only one of those 3 pts had been treated according to the intensive arm. With a median follow up of 1.36 years the estimated incidence rate at 1 and 2 years are 0.70% (95% CI .40-1.22)and 1.17% (95% CI .70-1.96) respectively (Figure 1). Conclusions Our data do not confirm previous findings of an excess risk of SPMs in association with the use of LEN and HDM in presenting patients, with 12/17 pts developing SPMs treated on the non intensive pathway that does not contain HDM. Most importantly only 0.4% of the patients enrolled within the intensive pathway developed a SPM, with only 2 of them receiving LEN maintenance. Longer follow up will help to further elucidate the risk of LEN associated SPMs. On behalf of the NCRI Haemato-Oncology subgroup Disclosures: Brioli: Celgene: Honoraria. Off Label Use: The presentation include the use of Lenalidomide as induction and as maintenance treatment for newly diagnosed multiple myeloma patients. Cook:Janssen: Honoraria, Research Funding, Speakers Bureau. Cavo:Celgene: 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; Millenium: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Onyx: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Bristol-Meyer Squibb: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. Morgan:Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Millenium: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Johnson and Johnson: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees.

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Persistent Improvement In Clinical Outcomes With Bortezomib-Thalidomide-Dexamethasone Vs Thalidomide-Dexamethasone Incorporated Into Double Autologous Transplantation For Multiple Myeloma: An Updated Analysis Of Phase 3 Gimema-MMY-3006 Study

Blood ◽

10.1182/blood.v122.21.2090.2090 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2090-2090 ◽

Cited By ~ 4

Author(s):

Michele Cavo ◽

Monica Galli ◽

Annalisa Pezzi ◽

Francesco Di Raimondo ◽

Claudia Crippa ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Board Of Directors ◽

Low Risk ◽

Standards Of Care ◽

Consolidation Therapy ◽

Phase 3 ◽

Advisory Committees ◽

Cox Regression Analysis

Abstract Over the last years, incorporation of novel agents into autologous stem cell transplantation (ASCT) has improved markedly the outcomes of younger patients with newly diagnosed multiple myeloma (MM). Superior results with experimental treatments vs previous standards of care have been frequently reported after preliminary analyses and need to be confirmed with longer follow up. The randomized phase 3 GIMEMA-MMY-3006 study was designed to compare bortezomib-thalidomide-dexamethasone (VTD) vs thalidomide-dexamethasone (TD) as induction therapy before, and consolidation after, double ASCT. Data from the initial analysis, with a median follow up of 36 months, demonstrated that patients randomized to the VTD arm enjoyed superior complete/near complete response (CR/nCR) rates after both induction and consolidation therapy, and had a significantly longer PFS compared to those prospectively assigned to the TD arm. We performed an updated analysis of the study after a median follow up of 59 months and results are herein reported. A persistent TTP and PFS benefit with incorporation of VTD into ASCT was confirmed. On an intention-to-treat analysis of 236 patients randomized to the VTD arm, median TTP was 62 months and median PFS was 57 months. The median values for 238 patients randomly assigned to the TD arm were 45 months for TTP (HR=0.64, p=0.001) and 42 months for PFS (HR=0.66, p=0.001) (Fig. 1). With the longer follow up of this analysis, an initial divergence between OS curves could be appreciated after 4 years, although the difference was not yet statistically significant at 6 years (75% for VTD vs 69% for TD). Superiority of VTD over TD for TTP and PFS was retained across prespecified subgroups of patients with high risk and low risk disease. In particular, PFS benefit with VTD was seen for patients age >60 years (HR=0.62, p=0.013) and younger than 60 years (HR=0.70, p=0.026), with ISS stage 1 (HR=0.59, p=0.009) and ISS stage 2-3 (HR=0.69, p=0.018), and for those with t(4;14) and/or del(17p) (HR=0.43, p<0.001) and with t(4;14) alone [t(4;14) positivity but lack of del(17p)] (HR=0.41, p=0.001). In comparison with patients with t(4;14) positivity who were randomized to TD, those assigned to the VTD arm had significantly longer PFS (median: 24 vs 53 months, HR=0.41, p=0.0007) (Fig. 2) and a trend towards longer OS (4-year estimates: 66% vs 81%, p=0.052). By the opposite, similar PFS curves were seen for patients in the VTD group regardless of the presence or absence of t(4;14) (Fig. 3). On multivariate Cox regression analysis, randomization to the VTD arm was an independent factor predicting for prolonged PFS (HR=0.64, P=0.001). Additional disease- and treatment-related variables independently affecting PFS included attainment of CR/nCR after both induction (HR=0.64, p=0.010) and consolidation therapy (HR=0.57, p<0.001), β2-m >3.5 mg/L (HR=1.7, p<0.001) and presence of t(4;14) and/or del(17p) (HR=2.0, p<0.001). On multivariate analysis, β2-m, cytogenetic abnormalities and attainment of CR/nCR after consolidation therapy were independently associated with OS. With an updated median follow-up of 49 months from the landmark of starting consolidation therapy, median PFS was 50 months for patients receiving VTD consolidation and 38 months for those treated with TD (HR= 0.69, P=0.015) (Fig. 4). Superior PFS with VTD vs TD consolidation therapy was observed for patients who failed CR/nCR after the second ASCT (HR=0.48, P=0.003) and was retained in both low risk and high risk subgroups. Finally, duration of OS from relapse or progression was similar between the two treatment groups (median, 42 for VTD vs 35 months for TD, p=0.47), even when bortezomib was incorporated into salvage therapy. In conclusion, this updated analysis of the GIMEMA-MMY-3006 study demonstrated: 1) a persistent PFS benefit with VTD vs TD in the overall population, as well as in subgroups of patients with high risk and low risk MM; 2) the ability of VTD, but not of TD, incorporated into double ASCT to overcome the adverse prognosis related to t(4;14); 3) the significant contribution of VTD consolidation to improved outcomes seen for patients randomized to the VTD arm; 4) the lack of more resistant relapse after exposure to VTD as induction and consolidation therapy compared to TD. A longer follow up is required to assess the OS benefit, if any, with VTD plus double ASCT. Disclosures: Cavo: Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Onyx: 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; 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. Tacchetti:Janssen and Celgene: Honoraria. Zamagni:Celgene: Honoraria; Janssen-Cilag: Honoraria. Caravita:Celgene: Honoraria, Research Funding. Brioli:Celgene: Honoraria.

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