Decreasing Costs and Clinic Wait Time While Maintaining Safety for Patients Receiving Lenalidomide, Bortezomib, and Dexamethasone (RVD) for Multiple Myeloma

Abstract Background Lenalidomide, bortezomib, and dexamethasone (RVD) is a standard front-line regimen for both transplant eligible and ineligible multiple myeloma (MM) patients. Based on original APEX study data, obtaining a complete blood count (CBC) before every administration of bortezomib has been recommended. Waiting for labs could add several hours to each visit. This can be inconvenient and costly for patients, payers, and institutions. There is a clear need to decease the frequency of labs drawn to promote increased cost-savings, improved patient safety, and decreased clinic wait times. Methods The primary objective of this study was to implement and evaluate a process change to decrease the frequency of labs for eligible patients on RVD for MM. First, an institutional review board-approved descriptive, retrospective study that included patients aged ≥ 18 years with MM receiving treatment with RVD was performed to assess trends in lab values. The objective of the retrospective review was to identify patients who can safely receive RVD without repeat labs prior to each bortezomib injection. Results from this retrospective review was presented to Dana-Farber Cancer institute (DFCI) and Massachusetts General Hospital myeloma clinicians, as well as the DFCI Pharmacy and Therapeutics committee. After approval was granted to implement institutional changes, we evaluated the impact of the process change. Results Retrospective study results Eighty-nine patients were included in the study. All patients had a platelet (PLT) count ≥ 75,000 cells/µL on day 1 of cycle 2 and beyond. Grade ≥ 3 thrombocytopenia developed in less than 3% of patients. Greater than 93% patients had an absolute neutrophil count (ANC) ≥ 1,000 cells/µL on day 1 of cycle 2 and beyond. Grade 3 and 4 neutropenia developed in 6.7% and 1.1% of patients, respectively. This study demonstrated that beyond the first cycle, patients with PLTs ≥ 75,000 cells/µL and an ANC ≥ 1,000 cells/µL on the first day of a cycle do not need labs prior to each administration of bortezomib in the cycle. These results provided the rationale for implementation of a new routine workflow. Workflow Implementation Implementation of a new workflow started on July 1, 2021 and included 71 adult patients receiving RVD for MM. First, a communication order was added to all RVD treatment plan templates in the electronic medical record specifying, "if on Day 1: ANC is ≥ 1,000 and PLTs are ≥ 75,000, no labs are required for remainder of that cycle." Following that, a flowchart was developed by nursing that instructed infusion nurses to request a cancelation of future labs within the current treatment cycle (if the patient met criteria). Workflow Evaluation The Centers for Medicare & Medicaid Services reimbursement rates for a comprehensive metabolic panel and CBC with differential is $18.33. Following the implementation of this workflow, we saved over $3,904 in unnecessary healthcare related costs per month (figure 2). The average time it takes for our patients on RVD to check into their lab appointment and have labs resulted is 55 minutes. It takes an average of 47 minutes for patients to have bortezomib administered after labs are reviewed and orders are released for preparation (figure 1). Ultimately, patients spend more than 50% of their time in clinic waiting for labs compared to the time it takes to have bortezomib prepared, delivered, and administered. The implementation of this new workflow resulted in saving 195 hours of clinic chair time per month (figure 2). This time saved results in improved quality of life for patients who already have multiple visits at various healthcare facilities. Spending less time in clinic and reducing the frequency of venipunctures could potentially reduce the risk of bleeding, bruising, and discomfort amongst a patient population that is typically older and more at risk for complications. Conclusion This study demonstrates that it is economical, resourceful, and safe to implement a workflow process aimed at decreasing the frequency of lab draws in patients receiving RVD for multiple myeloma. It allowed our institution to maximize chair time that could be used for other patients and generate additional value-added revenue. This is particularly very important with the Covid-19 pandemic, where reducing several hours of wait time will keep our patients and staff safer. Figure 1 Figure 1. Disclosures Munshi: Legend: Consultancy; Janssen: Consultancy; Abbvie: Consultancy; Adaptive Biotechnology: Consultancy; Karyopharm: Consultancy; Oncopep: Consultancy, Current equity holder in publicly-traded company, Other: scientific founder, Patents & Royalties; Takeda: Consultancy; Amgen: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy.

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Incidence of Febrile Episodes During Stem Cells Mobilization After High Dose Cyclophosphamide Chemotherapy and G-CSF (filgrastim or lenograstim) Administration in Multiple Myeloma Patients: Preliminary Final Results.

Blood ◽

10.1182/blood.v114.22.4560.4560 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4560-4560

Author(s):

Enrico Orciuolo ◽

Gabriele Buda ◽

Emerenziana Marturano ◽

Elisa Mauro ◽

Giuseppe Milone ◽

...

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Conflicts Of Interest ◽

Treatment Plan ◽

High Dose ◽

Absolute Count ◽

Functional Block ◽

Grade 3 ◽

Febrile Episodes

Abstract Abstract 4560 Introduction The G-CSF, primary regulator of granulopoiesis, has shown its efficacy in reducing duration of neutropenia after chemotherapy or myelosuppressive therapy. In these situations G-CSF, accelerating the granulocytous reconstitution, may enable a significant reduction of the incidence, duration and severity of infection. Commercially formulations of rHu-G-CSF include lenograstim, a glycosylated form, and filgrastim, a non-glycosylated form. Glycosylation of the molecule contribute to pharmacokynetis advantages and to higher affinity to specific receptor. Additionally, lenograstim exposed neutrophils maintain unchanged all their functions in vitro, while filgrastim exposed neutrophils present functional defects due to higher adhesivity, cytoscheletric alterations and a more immature phenotype. Aim On these bases, we hypotized that lenograstim may prevent febrile episodes (FE) and reduce their lasting in patients with chemotherapy derived neutropenia more efficiently than filgrastim. Primary endpoint is the incidence of FE (ClinicalTrials.gov ID: NCT00932217). Patients and methods starting from April 2005, 180 multiple myeloma patients achieving high dose cyclophosphamide for stem cells mobilization were enrolled in 11 Italian Centers. Treatment plan consisted in: high dose cyclophosphamide (3 or 4 g/sqm) on day 1, G-CSF (random 1:1 on the base of a generated random list: filgrastim or lenograstim) 30 MU/day from day +4 to +9, 60 MU/day from day +10 to the achievement of an optimal CD34+ cell count for staminoapheresis. FE, significant if equal or higher than 38 °C for at least 2 different determinations, were recorded till day +30. Results 176 of 180 patients received scheduled treatment and are eligible for final analyses. All 176 patients underwent post-chemo grade 4 neutropenia and G-CSF was administered starting from day +4. FE were recorded in 26 pts, 16 in the filgrastim arm (89 total patients) and 10 in the lenograstim arm (87 total patients). The global fever incidence was 14.77%, 17.98% with filgrastim and 11.49% with lenograstim. However, to demonstrate functional block of filgrastim exposed neutrophils, FE have been related to neutrophil absolute count. Related to the neutropenia grade, 8 FE are recorded with filgrastim (8.99%) and 1 FE with lenograstim (1.15%) with absolute neutrophil count >500/μL (grade 3) (chi square test with Yates' correction: p=0.0436); this difference is still evident when neutrophils are >1000/μL (grade 2), with 7 episodes with filgrastim (7.87%) versus 1 (1.15%) with lenograstim. Conclusions Lenograstim is associated with a reduced global incidence of FE in multiple myeloma patients undergoing to high dose cyclophosphamide and stem cells mobilization when compared to filgrastim. Additionally, excluding the time frame when neutrophils are not yet recovered (neutrophils <500/μL; grade 4 neutropenia) and G-CSF effects may not be demonstrated, filgrastim treated patients present, when compared to lenograstim treated patients, an higher FE incidence at neutrophil absolute count recovery (both with grade 3 and grade 2 neutropenia), confirming the functional block of filgrastim exposed neutrophils described in vitro. On the contrary, lenograstim allows to recovery normally functional neutrophils as demonstrated by the very low incidence of FE (1.15% with neutrophils >500/μL) in treated patients. Disclosures: No relevant conflicts of interest to declare.

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CHANGE IN COMMUNICATION MANAGEMENT ROLES DUE TO GLOBALIZATION: A CASE OF COMMUNICATION MANAGEMENT COMPETENCIES MAPPED BY INTERNATIONAL PROFESSIONAL PUBLIC RELATIONS ASSOCIATIONS (2015–2020)

Ekonomicko-manazerske spektrum ◽

10.26552/ems.2021.2.65-86 ◽

2021 ◽

Vol 15 (2) ◽

pp. 65-86

Author(s):

Renata Matkevičienė ◽

Lina Jakučionienė

Keyword(s):

Public Relations ◽

Value Added ◽

Management Competencies ◽

Communication Management ◽

Study Results ◽

Managerial Training ◽

Management Roles ◽

The Impact ◽

Constant Improvement

Research background: The role of communication has now become much more critical than during previous periods, not only to compete with other organisations in the stream of communicating messages but also to develop and implement organisational strategies and support the organisation’s top-level managers and decision-makers. The goal of public relations (PR) associations is to develop PR professionals’ competencies. Comprehensive research at the European level signals the need for constant improvement of competencies, especially business development and technologies (Zerfass et al., 2020; Adi, 2019). A vast majority of practitioners across Europe highlight the importance of digitalising stakeholder communications and building a digital infrastructure to support internal workflows (Zerfass et al., 2021). However, instead of technical and managerial training, PR practitioners continue to overwhelmingly offer communication training and development opportunities (Tench et al., 2013; Zerfass et al., 2018; MacNamara et al., 2017; Feldman, 2017; The USC Annenberg Centre for Public Relations, 2017; Communicating AI, 2019). There are discrepancies between the perceived importance of competencies and the current qualifications of professionals due to digital transformation and changes impacted by globalisation. Purpose: To identify changes in PR specialists' competencies due to the impact of globalisation. Methods: Content analysis of information provided in the webpages of international professional PR associations for the period 2015–2020. Findings and value added: The study results show that professional PR associations do not respond to the challenges of the changing environment in a timely manner by providing training, but present and discuss relevant topics with the help of specialists from other fields while encouraging the sharing of good practices. Such a functioning position occupied by professional PR associations in developing the model of competence for PR specialists reveals that PR associations are engaged in strengthening or maintaining competencies, but not developing them.

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Treatment Patterns and Outcomes in Lenalidomide-Exposed Multiple Myeloma Patients in Real-World Settings: A Multi-Center Retrospective Study

Blood ◽

10.1182/blood-2021-148724 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 5012-5012

Author(s):

Maria Eduarda Couto ◽

Marina Borges ◽

Maria José Bento ◽

Rita Calisto ◽

Marta Daniela Marques Magalhaes ◽

...

Keyword(s):

Multiple Myeloma ◽

Retrospective Study ◽

Real World ◽

Treatment Patterns ◽

University Hospital ◽

Real World Data ◽

Treatment Pathways ◽

Start Date ◽

Medical Needs ◽

The Impact

Abstract Background Treatment of multiple myeloma (MM) has changed significantly in recent years with the availability of novel agents including monoclonal antibodies (mAbs), proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) such as lenalidomide. Despite lenalidomide becoming a standard of care across all lines of myeloma therapy, the population of MM patients refractory to lenalidomide and their real-world clinical management has been poorly studied so far, especially outside the reality of interventional clinical trials (Moreau et. al. Blood Cancer J. 2019). With these considerations in mind, we have performed a retrospective study using two databases to better understand treatment patterns and outcomes of MM patients who were treated with lenalidomide and subsequently became refractory to it. This builds on work previously conducted at other data sources (Willenbacher et. al. EHA Library 2020). Aims The objective of this study was to describe the treatment patterns and outcomes of MM patients exposed to lenalidomide, with a focus on refractory patients, as defined by IMWG (International Myeloma Working Group) consensus, in a real-world clinical setting. Methods The study utilised databases from two participating members of the IQVIA MM real world evidence network: University Hospital Frankfurt (Frankfurt) (Germany) and Portuguese Oncology Institute of Porto (IPO-Porto) (Portugal). Since the native format of databases from participating sites differs, key concepts were harmonised based on pre-agreed definitions. The study population included patients with an initial diagnosis of MM between 01/01/2012 and 31/12/2018 based on the IMWG criteria, were 18 years old or older at the time of diagnosis and received two or more cycles of lenalidomide treatment, alone or in combination, at any dose, excluding patients who only received lenalidomide as maintenance therapy. Patients were defined as refractory to lenalidomide treatment if they progressed on treatment or within 60 days following the end of lenalidomide treatment (excluding maintenance setting). Kaplan-Meier curves were produced to evaluate the time to next treatment (TTNT) and overall survival (OS) for lenalidomide exposed and lenalidomide refractory patients. TTNT was defined as the time between the start date of the line of lenalidomide therapy and the start date of the next line of therapy (LoT) or death due to any cause. OS was defined as the time between the start date of the line of lenalidomide therapy and death due to any cause. Results The cohort included 55 and 42 MM lenalidomide-exposed patients from Germany and Portugal respectively. In Germany, 80% were initially exposed to the lenalidomide in LoT 1, whilst in Portugal 71% received initial lenalidomide treatment in LoT 3. In Portugal, following lenalidomide refractoriness, the majority (78%) of patients received chemotherapy and steroids only whilst in Germany a range of treatment types was observed (mAb-based 33%; PI-based 11%; PI/IMiD combo 11%; mAb/IMiD combo 11%; chemotherapy and steroids only 11%; other 22%). The median OS in months for lenalidomide-exposed refractory patients was 7 in Portugal and 31 in Germany; the median OS for non-refractory patients was 40 in Portugal and was not reached in Germany. The median TTNT in months for lenalidomide-exposed refractory patients was 4 in Portugal and 15 in Germany; the median TTNT for non-refractory patients was 14 in Portugal and 53 in Germany. Conclusion The analysis of real-world data across two countries, showed heterogeneity in lenalidomide treatment patterns, with first exposure typically occurring in LoT 1 or 3. This has led to differences in the calculated TTNT and OS, and as such the results between the two countries cannot be directly compared. The OS from diagnosis for this cohort is being assessed and will provide an insight on the impact of different treatment pathways. Patients who became refractory to lenalidomide moved on to their next treatment much quicker after exposure vs patients who were not refractory to lenalidomide; similarly, patients who became refractory to lenalidomide had shorter OS than patients who were not refractory. Patients typically became refractory early in their treatment journey, indicating a growing population with unmet medical needs. Figure 1 Figure 1. Disclosures Metzler: GSK: Consultancy; Takeda: Consultancy; Janssen: Consultancy; AstraZeneca: Consultancy; Amgen: Consultancy; BMS: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy.

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The Impact of Intellectual Capital Efficiency in Business Reengineering: An Empirical Study on the Industrial Companies Listed on the ASE

International Journal of Business and Management ◽

10.5539/ijbm.v14n2p187 ◽

2019 ◽

Vol 14 (2) ◽

pp. 187

Author(s):

Omar Fareed Shaqqour

Keyword(s):

Intellectual Capital ◽

Stock Exchange ◽

Value Added ◽

Intellectual Ability ◽

Industrial Firms ◽

Engineering Approach ◽

Industrial Companies ◽

Study Results ◽

Capital Efficiency ◽

The Impact

The redesign of administrative strategic processes and polices from the root to realize the value added in the organization is called re-engineering approach, where the employees who have the knowledge, intellectual ability and skills that give them the ability to innovate and achieve the objectives of the organization, is called intellectual capital efficiency.     Knowing the importance of an intellectual capital efficiency of the company and its contribution to provide the requirements of applying re-engineering in the company and its ability to motivate the company to implement this approach, Is important and vital. This study aims to identify the impact of intellectual capital efficiency in re-engineering on industrial firms listed on the Amman Stock Exchange ASE. To achieve this goal, the researcher measured the intellectual capital efficiency by Pulic model, and the business re-engineering through a questionnaire to measure three themes related to re-engineering, the business, extent of support the company's management to apply the business re-engineering approach, the availability of the requirements of re-engineering, and the extent of applying the reengineering approach. The study sample consisted from 50 industrial companies listed on the ASE, during the study period (2014- 2017), the study used SPSS and Excel to identify the descriptive characteristics of the variables of the study, and analysis the data, and it was also used regression analysis to test the hypotheses of the study. Study results concluded that intellectual capital efficiency positively impact in supporting the company's management to apply the business re-engineering approach in the industrial companies listed on ASE, and the results also showed that the intellectual capital efficiency positively impact in the providing of the business re-engineering requirements in these companies, finally, the study finds that intellectual capital efficiency positively impact in the applying the business reengineering approach in these companies. The study recommended to increase the interest for intellectual capital and business reengineering, and the study also recommended to increase awareness among workers in the accounting departments of the importance of the subject of intellectual capital efficiency and business reengineering.

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Impact of on-study corticosteroid use on efficacy and safety in the phase III AFFIRM study of enzalutamide (ENZA), an androgen receptor inhibitor.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.6 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 6-6 ◽

Cited By ~ 29

Author(s):

Howard I. Scher ◽

Karim Fizazi ◽

Fred Saad ◽

Kim N. Chi ◽

Mary-Ellen Taplin ◽

...

Keyword(s):

Progression Free Survival ◽

Phase Iii ◽

Castration Resistant Prostate Cancer ◽

Post Hoc Analysis ◽

Castration Resistant ◽

Study Results ◽

Psa Progression ◽

Grade 3 ◽

Post Hoc ◽

The Impact

6 Background: ENZA increased median overall survival (OS) by 4.8 mo (P <0.001, HR 0.63) vs placebo (PBO) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) post-docetaxel in AFFIRM (HI Scher et al, NEJM 2012). Corticosteroids (CS) can activate AR signaling in nonclinical models (J Richards, Can Res 2012). In a multivariate model of AFFIRM data baseline CS use was associated with reduced OS (HI Scher et al. ESMO 2012 abstract 899PD). The impact of CS use during study treatment in AFFIRM was evaluated to test if concomitant CS use is also associated with inferior outcomes. Methods: Pts were randomized 2:1 to ENZA 160 mg/d or PBO. Pts were allowed but not required to take CS. OS was the primary endpoint. In a post-hoc analysis On-study CS use was defined as oral CS user for ≥ 1 day on study. Results: On study CS use was 48% in ENZA and 45% in PBO pts. Prognostic factors were slightly better in the no CS group compared to the CS group. Use of CS regardless of treatment was associated median OS of 11.5 mo (95% CI: 10.5, 13.0) for CS pts vs median OS NM (NM, NM) for no CS pts (HR=0.40; 95% CI: 0.33, 0.48). ENZA was consistently superior to PBO for OS, radiographic progression free survival (rPFS) and time to PSA progression (TTPP), regardless of CS use (Table). Pts on CS had higher rates of grade 3 - 4 adverse events (AE) compared to no CS pts: 63.3% vs 34.4% respectively. Conclusions: In this post-hoc analysis, on study CS use was associated with reduced OS and higher rates of grade 3 -4 AEs in mCRPC pts post-docetaxel. While CS pts had worse outcomes, ENZA was consistently superior to PBO regardless of on study CS use. The inferior outcomes in CS pts may be due to unmeasured confounders or the biologic properties of CS use itself. Clinical trial information: NCT00974311. [Table: see text]

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Retrospective study to assess the impact of hepatitis C virus infection on the prognosis and management of multiple myeloma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e20001 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e20001-e20001

Author(s):

David Kaldas ◽

Andrew Wahba ◽

Radwa Hamdy Azab ◽

Ehab Mostafa Elnakoury ◽

Nagla Fawzy Abdel Karim ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Hepatitis C Virus ◽

Retrospective Study ◽

Hepatitis C ◽

Progression Free Survival ◽

Hcv Infection ◽

Cytotoxic Agents ◽

Free Survival ◽

The Impact

e20001 Background: Multiple Myeloma (MM) is a neoplasm of the post-germinal center, terminally differentiated B-cells. MM accounts for 1% of all types of cancer and 10% for all hematologic malignancies. Chronic hepatitis C virus (HCV) is an infection that affects over 71 million patients worldwide. Cytotoxic agents and immunosuppressive therapy as steroids are the main line of therapy in lymphoid malignancies, but these drugs may exacerbate chronic viral hepatitis and cause uncontrolled replication of hepatitis viruses. The impact of HCV infection on MM patients remains unclear. Objective: To assess the impact of HCV infection on the prognosis and management of MM patients. Methods: A 10-year retrospective study of MM patients was conducted at Cairo University Clinical Oncology Department from January 2009 to April 2019. Results: During this time, 150 patients were diagnosed with MM, 109 (72.7%) were HCV negative, 24 (16%) were HCV positive, and 17 (11.3%) with unknown HCV status. The median age was 51 and 54 years for HCV negative and positive groups respectively, with a statistically insignificant difference (p-value > 0.2). In the multivariate analysis, HCV infection was not an independent factor related to overall survival (OS), however age, creatinine and hemoglobin levels correlated significantly with OS (p < 0.009, 0.008, 0.031 respectively). The median OS for the HCV negative group was 31.11 months (95% CI: 22.62 - 39.61) compared to 37.66 months (95% CI: 7.19 - 68.13) for the HCV positive group. The median progression-free survival (PFS) for all patients was 18.9 months, for HCV positive patients was 15.36 months (95% CI: 13.18 – 17.54), and for HCV negative patients was 20.49 months (95% CI: 14.13 – 26.85). Age below 60 years and creatinine level less than 2 mg/dL were statistically significant for favorable disease-free survival (DFS) (p < 0.030, 0.034 respectively). Conclusions: Age, creatinine and hemoglobin levels are significant prognostic factors in MM but HCV status doesn’t affect the overall survival or progression-free survival. HCV infection should not contraindicate MM therapy.

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A Phase II Study of Oral Panobinostat (LBH589) in Adult Patients with Advanced Refractory Multiple Myeloma

Blood ◽

10.1182/blood.v112.11.2774.2774 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2774-2774 ◽

Cited By ~ 14

Author(s):

Jeffrey Lee Wolf ◽

David Siegel ◽

Jeffrey Matous ◽

Sagar Lonial ◽

Hartmut Goldschmidt ◽

...

Keyword(s):

Multiple Myeloma ◽

Phase Ii ◽

Light Chain ◽

Clinical Investigation ◽

Single Agent ◽

Study Drug ◽

Bone Lesions ◽

Durable Response ◽

Study Results ◽

Grade 3

Abstract Panobinostat (LBH589) is a highly potent pan-deacetylase inhibitor (DACi), which induces cytotoxicity at <10nM in multiple myeloma (MM) cell lines resistant to conventional therapies. It modulates 2 targets implicated in MM by controlling cell proliferation and survival through HSP90 and inducing apoptosis through the aggresome pathway. Here we report the preliminary results of a Phase II, single arm, multicenter study of panobinostat in patients with measurable MM disease who had received at least 2 prior lines of therapy (including bortezomib and lenalidomide or thalidomide) and who were also refractory to their most recent line of therapy. The study was designed to assess: response rate (CR/PR) by the IBMTR/EBMTR criteria, safety, and tolerability of 20 mg/day of oral panobinostat given on a Monday/Wednesday/Friday (MWF) dosing schedule. 3 or more responders in 25 patients in stage 1 of the study were required for the initiation of Stage 2. A total of 38 pts (24 males, 14 females; median age 61 years [43–72]) have been enrolled between February and October 2007. Median time since last prior therapy was 33 days, median number of prior therapies was 5 (2–12). Median treatment duration was 45 days (5–377 days). Overall, panobinostat was well tolerated, and no new safety signals were reported. Mild or moderate level of nausea, as well as fatigue/asthenia, occurred in half of the patients. The most common Grade 3/4 AEs were cytopenias, with neutropenia, thrombocytopenia, and anemia in 32%, 26%, and 16% of patients, respectively. Other Grade 3/4 AEs included infections: 8 occurrences (3 of pneumonia; 2 of septic shock; and back pain, hypercalcemia, and hypokalemia in 3 pts each). No cardiac (including significant QTc prolongation, pericarditis, or pericardial effusion) or thromboembolic events were reported. SAEs potentially related to study drug were observed in 3 pts and included nausea (2), diarrhea and vomiting (1), and reduced general condition (1). 5 patients discontinued therapy for AE: 2 due to acute renal failure which was progression coincident, 2 due to elevated creatinine suspected to be study drug related, and 1 for worsening on study of peripheral neuropathy (non-related). 1 patient died on study due to a cerebral vascular accident (assessed by the investigator as not study drug related). QT intervals (QTcF) were monitored per study protocol and out of >1500 post dose ECGs, 1 pt showed a Grade 2 prolongation of QTcF value above 480 ms, 2 pts had a QTcF increase of ≥60 ms compared to baseline, and 10 pts had a minimal 30–<60 ms increase of QTcF compared to baseline. A clinical durable response was observed in a 43-yr-old female patient, whose urine kappa light chain MM with bone lesions was progressing on lenalidomide/dexamethasone prior to enrollment. The patient had 5 prior lines of therapy, including auto-SCT twice (5 years apart), bortezomib, and thalidomide. Response was rapid, with a 60% reduction of urine M protein at Cycle 2 and 90% at Cycle 4. PR was confirmed in Cycle 7, including stabilized bone lesions, and is sustained at 11 months on therapy with urine light chain stable below the “measurable disease” level of 100mg/24hrs and urine IF still positive, thus a VGPR. A quick and dramatic reduction in angiogenesis markers (VEGF, sVEGFR1, and bFGF) was seen starting on Cycle 1, Day 8 of treatment, as well as a reduction (50%) of seric free light chain, which continued further throughout the later cycles. A second patient on study for >12 months is continuing to show clinical benefit after failing 10 prior lines of therapy (including Auto-SCT, bortezomib, lenalidomide, and thalidomide) and is maintaining MR. Stable disease observations of >3 months occurred in 3 pts. Single-agent, oral panobinostat at 20 mg/day thrice weekly was well tolerated and safe in this study. Evidence has since been obtained from clinical responses in patients with various hematological malignancies that higher doses of single-agent panobinostat can provide more optimal dosing schedules than the 20 mg dose. Thus, although the current study at the 20 mg schedule did not meet its objective, the observation of 1 durable VGPR and 1 durable and ongoing MR, in addition to transient disease stabilization in 3/38 patients, are encouraging results, especially at this low dose, warranting further clinical investigation of panobinostat. The analysis of final study results will be presented.

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Impact of Deletion 17p On the Outcome of Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma.

Blood ◽

10.1182/blood.v120.21.3099.3099 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3099-3099

Author(s):

Caitlin L. Costello ◽

Edward D. Ball ◽

Sue Corringham ◽

Hongying Li ◽

Karen Messer

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

High Risk ◽

Complete Remission ◽

Stem Cell Transplantation ◽

Chromosomal Abnormalities ◽

Treatment Plan ◽

Normal Cytogenetics ◽

The Impact

Abstract Abstract 3099 Background: The development of a risk-stratification model that relies on molecular cytogenetic markers to assess disease aggressiveness and provide therapeutic guidance would be beneficial for the management of patients with multiple myeloma (MM). High-risk cytogenetic abnormalities, including deletion 17p (del17p), are known to confer a poor prognosis. Intensified consolidation with high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) following induction therapy has been proposed as the preferred initial treatment for high-risk MM, such as del17p. With this background, we report the impact of del17p on the timing and outcome of transplant in patients with MM. Methods: We performed a retrospective review of 226 patients with MM who underwent HDT/ASCT at the University of California, San Diego Moores Cancer Center between 1/2000 and 7/2011. Conventional cytogenetic analyses were utilized for all patients either at diagnosis or at relapse, but prior to ASCT. Fluorescence in situ hybridization was also assessed when available. The primary objective was to evaluate the impact of del17p, a known high-risk chromosomal abnormality, on the overall survival (OS) and progression-free survival (PFS) after ASCT, compared with patients without chromosomal abnormalities. A secondary objective was to assess the OS and PFS for patients with del17p who received ASCT within a year of diagnosis, compared with those who underwent ASCT more than 12 months from diagnosis. Results: In 226 patients with conventional cytogenetic data prior to ASCT, chromosomal abnormalities were noted in 82 (36%) patients. Of these, 21 (25%) patients harbored a del17p abnormality. Table 1 shows the patient characteristics and ASCT outcomes. Prior to undergoing ASCT, 4 (19%)patients with del17p achieved a complete remission (CR) or stringent complete remission (sCR), and 6 (29%) achieved a CR or sCR after ASCT. In patients without chromosomal abnormalities, 19 (13%) achieved CR or sCR prior to ASCT, and 45 (31%) achieved it after ASCT. Median follow-up of surviving patients was 47 months (range 5–283). Median PFS after ASCT in patients with del17p and normal cytogenetics were 8.3 months (95%CI: 4.6-N/A) and 33 months (95%CI: 21.7–61.8), respectively (HR 2.15, 95%CI: 1.19–3.89; p=0.011) (Figure 1). Median OS after ASCT in patients with del17p and normal cytogenetics were 47.5 months (95%CI: 19.9-N/A) and 68 months (95%CI 51.1-N/A), respectively (HR: 2.27, 95%CI 1.15–4.48; p=0.018) (Figure 2). Median PFS in patients with del17p who received an ASCT after 12 months and within 12 months from diagnosis was 6.13 months (95%CI: 2.7-NA) and 22.6 months (95%CI: 5.4-NA), respectively (HR=1.22, 95%CI 0.40–3.82; p=0.71). Median OS in del17p patients who received an ASCT after 12 months and within 12 months from diagnosis was 65.6 months (95%CI: 19.3-NA) and 47.5 months (95%CI: 19.9-NA), respectively (HR=0.97, 95%CI 0.26–3.62; p=0.96). Conclusions: In this single center study with long follow up, we demonstrate that a del17p abnormality in MM confers a shorter PFS and OS after ASCT. Furthermore, the use of HDT/ASCT as part of the upfront treatment plan within 12 months of diagnosis does not significantly affect the outcome in patients with a del17p abnormality. Further studies are required to better define a risk-stratified treatment plan for this subset of high-risk multiple myeloma. Disclosures: No relevant conflicts of interest to declare.

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Phase II trial of intraperitoneal paclitaxel in carcinoma of the ovary, tube, and peritoneum: a Gynecologic Oncology Group Study.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.8.2620 ◽

1998 ◽

Vol 16 (8) ◽

pp. 2620-2624 ◽

Cited By ~ 101

Author(s):

M Markman ◽

M F Brady ◽

N M Spirtos ◽

P Hanjani ◽

S C Rubin

Keyword(s):

Residual Disease ◽

Treatment Plan ◽

Gynecologic Oncology ◽

Complete Response ◽

Phase Iii ◽

Maximum Diameter ◽

Gynecologic Oncology Group ◽

Eligibility Criteria ◽

Grade 3 ◽

The Impact

PURPOSE To determine the response rate of intraperitoneal (i.p.) paclitaxel in patients with small-volume residual carcinomas of the ovary, fallopian tube, or peritoneum. PATIENTS AND METHODS Eligibility criteria included patients with one of the cancers noted above, with the largest residual disease 0.5 cm or less in maximum diameter at the end of second-look surgery, and prior treatment with systemic paclitaxel was permitted. The treatment plan was paclitaxel 60 mg/m2 i.p. weekly for 16 weeks, followed by surgical evaluation in patients without evidence of disease progression. RESULTS Of 80 patients entered onto the study, 76 were eligible, of whom 86% were considered to be potentially cisplatin-sensitive. Although five patients (7%) did not complete the first course of therapy because of catheter leakage or blockade, 53 patients (70%) received all 16 planned courses. Only 14 patients (18%) received fewer than 11 courses. Treatment was well tolerated, which included only moderate abdominal pain (grade 2, 12 patients; grade 3, one patient) and minimal neutropenia (grade 2, three patients; grade 3, one patient). Of 28 assessable patients with microscopic disease at the start of i.p. therapy, 17 patients (61%) achieved a surgically defined complete response (CR). Only one of 31 patients (3%) with any macroscopic disease achieved a CR. Of the eligible patients, 18 of 76 (24%) achieved a CR. CONCLUSION Salvage i.p. paclitaxel is tolerable and active in patients with microscopic residual disease. The impact of this treatment strategy on survival remains to be assessed in a phase III trial.

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Activity and Safety of Lenalidomide and Dexamethasone in Multiple Myeloma Patients with Advanced Renal Failure: a Spanish Multicenter Retrospective Study.

Blood ◽

10.1182/blood.v114.22.1886.1886 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1886-1886 ◽

Cited By ~ 4

Author(s):

Monica Roig ◽

Angela Ibañez ◽

Inmaculada García ◽

Juan A. Vera, ◽

Carlos Aguilar ◽

...

Keyword(s):

Multiple Myeloma ◽

Renal Failure ◽

Partial Response ◽

Progressive Disease ◽

Conflicts Of Interest ◽

Infectious Complications ◽

Close Monitoring ◽

Starting Dose ◽

Grade 3 ◽

The Impact

Abstract Abstract 1886 Poster Board I-909 Background: Approximately 30% of patients with multiple myeloma (MM) present with baseline renal impairement, with 1% to 13% having renal failure requiring dialysis support. The severity of renal impairment significantly affects the prognosis of patients with MM and has been associated with shorter survival or early death. Lenalidomide is an immunomodulating agent indicated for the treatment of MM patients after one prior therapy. Lenalidomide is primarily excreted unchanged by the kidney, adjustements to the starting dose are recommended in patients with moderate or severe renal impairement and in patients on dialysis. For patients with end stage renal disease (CLCr < 30 mL/min) requiring dialysis, the recommended starting dose is 5 mg/day. However, experience in patients with MM and dialysis support is limited. To further examine the safety and activity of lenalidomide-based therapy in these patients, we underwent a retrospective analysis in patients with MM who required dialysis at the time of lenalidomide administration. Methods: Fifteen patients (10 M/5 F; median age, 70 years, range 55–77) with relapsed MM from 10 Spanish hospitals received lenalidomide-based therapy between 2007 and 2009. All patients were on dialysis at the time of lenalidomide administration. Median (range) number of therapies previously administered was 2 (1–4) and median time between diagnosis and lenalidomide treatment was 14 months (range, 5–50). Eighty-seven percent of patients received lenalidomide at a dose of 15 mg/day three times weekly after dialysis given in combination with dexamethasone. Patients were given a median of seven 28-day cycles (range, 1–22 cycles) of lenalidomide treatment. Antithrombotic prophylaxis was administrated in fourteen patientes and consisted of low molecular weight heparin (five cases, 36%), oral anticoagulation (four cases, 29%), antiplatelet therapy (three cases, 21%), and combination of the above agents (two cases, 14%). Results: Overall, 13 (87%) patients experienced adverse events, with grade 3 neutropenia as the most common (8 patients). Seven patients (47%) developed grade 3–4 infectious complications (3 bacteremias, 1 infection of arterio-venous fistula, 1 septic arthritis, 1 central venous line infection, and two pneumonias in the remaining patient). No patient developed thromboembolic complications. Fourteen patients were evaluable for response: 4 had complete response (29%), 1 a very good partial response (7%), and 3 partial response (21%). In addition, 4 patients had stable disease (29%) and 2 (14%) did not respond. One patient became independent of dialysis following lenalidomide-based treatment. As of July 2009, seven (47%) patients have died, four due to infectious complications and three as a result of progressive disease. Eight patients are still alive, six of them continue on lenalidomide treatment and two discontinued therapy due to liver toxicity (1 case) and progressive disease (1 case). Conclusion>: These results suggest that lenalidomide-based regimens can be used in MM patients requiring dialysis, with a good response rate. The high incidence of neutropenia and infectious complications highlights the need of a close monitoring of these patients. Currently ongoing studies will more formally evaluate the impact of lenalidomide-based regimens in this patient population. Disclosures: No relevant conflicts of interest to declare.

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