scholarly journals Evidence of Improved Knowledge and Skills Among Hematologists/Oncologists Participating in Online CME-Certified Activities

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4958-4958
Author(s):  
Lauren Willis ◽  
Emily S. Van Laar ◽  
Tristin Abair ◽  
Megan Whitney ◽  
Caitlin Costello ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Best Practices ◽  
Research Funding ◽  
Hematologic Malignancies ◽  
Newly Diagnosed ◽  
Community Based ◽  
Relative Percentage ◽  
Percentage Improvement ◽  
The Impact

Abstract Background: Several regimens are currently available for the treatment of newly diagnosed or relapsed/refractory multiple myeloma (R/R MM). This has subsequently led to the development of a variety of novel management strategies. Because of the rapidly changing treatment landscape, it is challenging for hematologists/oncologists (hem/oncs), particularly those in community-based settings, to stay current on recent data and clinical practice guidelines. Aim: The objective of this study was to determine if a curriculum of online continuing medical education (CME) activities could improve the knowledge, skills, and confidence of hem/oncs as it relates to the treatment of patients with MM. Methods: The curriculum contained online CME-certified activities for clinicians that focused on personalizing treatment, managing adverse events (AEs), and integrating new data and agents into clinical practice for the treatment of MM. All activities were developed with input from a steering committee of expert myeloma physicians and a nurse practitioner. There were 10 activities included in this analysis. The impact of education was examined using a repeated-pair design with a pre-/post-assessment. Questions from all activities were grouped into learning topics. Mean knowledge/skill was calculated across all activities, and included questions designed for longitudinal analysis. Statistical significance was assessed using a McNemar's test (5% significance level, P <.05). Data was collected from when the first activity posted on November 11, 2020 through July 8, 2021. Results: A total of 570 hem/oncs were included in this analysis. A majority practiced in community-based settings (51%), specialized in hematologic malignancies (specialists, 51%), and cared for 1 to 10 patients with MM in a typical month (70%). The percentage of correct responses pre- and post-education across multiple curriculum activities are displayed by subgroup in the Table. Confidence was assessed for various topics on the scale of 1-not confident to 5-very confident. Hem/oncs were considered confident if they rated their confidence a 4 or 5. The pre-/post-education percentage of hem/oncs who were confident (4 or 5 on a scale of 1 to 5) personalizing treatment: 18%/23% academic (P <.01, relative percentage improvement, RI +56%), 17%/31% community (P <.001, RI +82%), 18%/30% specialists (P <.001, RI +67%), 13%/25% average 10 or fewer patients with MM per month (P <.001, RI +91%). Conclusions: The series of CME-certified activities had a significant, positive impact on knowledge, skills, and confidence across all learning themes for all hem/oncs, but especially community-based hem/oncs and specialists in hematologic malignancies. For almost all learning themes, community-based hem/oncs demonstrated similar or higher knowledge/skills post-education than their academic-based counterparts. Community-based hem/oncs also demonstrated larger relative improvements in knowledge/skills than academic-based hem/oncs. Hem/oncs who saw fewer patients with MM on average per month demonstrated a larger relative percentage improvement with these learning themes: foundational knowledge, knowledge of clinical trial data, knowledge of treatment regimens, knowledge of SDM. Hem/oncs who saw a higher number of patients with MM on average per month demonstrated larger relative percentage improvement with these learning themes: knowledge of MRD, skills personalizing treatment, knowledge of AEs, skills managing AEs, skills using SDM. This analysis shows that online CME using multimedia formats can significantly improve the knowledge, skills, and confidence of hem/oncs in multiple areas related to best practices for treating patients with newly diagnosed or R/R MM. The impact on community-based hem/oncs was significant and closed large knowledge and skill gaps compared to their academic peers. Results also suggest the following areas warrant further education: case-based application of treatment options and AE management as well as best practices for individualizing treatment. Acknowledgements: Sukhbir Bahra contributed to data analysis for this research. These CME activities were supported by an independent educational grant from AbbVie, Bristol Myers Squibb, GlaxoSmithKline, Karyopharm Therapeutics, Oncopeptides, and Sanofi Genzyme. Reference: https://www.medscape.org/sites/advances/multiple-myeloma Figure 1 Figure 1. Disclosures Krishnan: BMS: Consultancy, Current equity holder in publicly-traded company, Speakers Bureau; MAGENTA: Consultancy; REGENERON: Consultancy; SANOFI: Consultancy; GSK: Consultancy; JANSSEN: Consultancy, Research Funding; City of Hope Cancer Center: Current Employment; Amgen: Speakers Bureau. Lonial: Takeda: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Consultancy, Honoraria, Research Funding; AMGEN: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Merck: Honoraria. Kurtin: Abbvie, Amgen, BMS, Incyte, Pharmacyclics, GSK, AstraZeneca, Takeda: Consultancy, Speakers Bureau. Mikhael: Janssen: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Karyopharm: Consultancy; Amgen: Consultancy; BMS: Consultancy; Oncopeptides: Consultancy; GSK: Consultancy. Landgren: Amgen: Honoraria; Janssen: Honoraria; Janssen: Research Funding; Janssen: Other: IDMC; Celgene: Research Funding; Amgen: Research Funding; Takeda: Other: IDMC; GSK: Honoraria.

New US Myeloma Registry (Connect MM® – The Multiple Myeloma Disease Registry): Features of Newly Diagnosed Patients In 2010

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5032-5032
Author(s):  
Brian G. M. Durie ◽  
Jatin J. Shah ◽  
Rafat Abonour ◽  
Cristina Gasperetto ◽  
Jayesh Mehta ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Staging System ◽  
Bone Lesions ◽  
Case Report Form ◽  
Newly Diagnosed ◽  
Community Based ◽  
Advisory Committees ◽  
Prior Therapy

Abstract Abstract 5032 Background: In the past decade, with the availability of novel therapies, the paradigm for myeloma management has changed. In 2010 it is especially important to understand baseline features and initial treatment decisions. The goal of the Connect MM® registry is to characterize patients with newly diagnosed active myeloma from 200 US sites. Approximately 80% of the patient population will be enrolled from community-based practices and 20% from academic centers. An electronic case report form was developed to collect clinical data, physician choices, patient health-related quality of life (HRQoL) and response, as well as data on survival end points. This is a prospective, observational, longitudinal study with a target accrual of 1,500 patients in 3 years, with a 5 year follow-up from the time of informed consent. There are no mandated treatments or clinical assessments. However, there are data collection requirements for diagnosis and disease monitoring. Results: Since late 2009, 340 patients from 135 sites have been accrued and were included in this interim analysis. Current study demographics include: 60% male, 83% white, and 14% black, with a median age of 67 years. Thus far, 97% have been enrolled from community-based practices. All patients met study enrollment criteria and had active myeloma at entry; prior monoclonal gammopathy of unknown significance (MGUS) was reported in 13% and smoldering MM in 8%. International Staging System (ISS) staging for evaluable patients were 26.3%, 36.4%, 37.3% for stages I, II, and III, respectively. Durie-Salmon Stage (A or B) were 13%, 35%, 52% for stages I, II, and III, respectively. Staging procedures included 82% skeletal survey; 44% computed tomography (CT); 40% magnetic resonance imaging (MRI); 7% positron emission tomography (PET); 2% PET/CT; and 4% had no imaging. International Myeloma Working Group (IMWG) CRAB criteria were assessed in all enrolled patients; 9% had hypercalcemia, 18% renal insufficiency, 36% anemia, and 66% had bone lesions. Median values were: calcium 9.5 mg/dL; serum creatinine 1.1 mg/dL; hemoglobin 10.9 gm/dL. Only 9% of patients had 3 or 4 CRAB features, while 49% had only 1 feature and 26% were asymptomatic (ECOG=0). The incidence of baseline peripheral neuropathy was 6%. Initial pain led to radiation therapy for 10% of patients, with 16% having vertebroplasty or kyphoplasty. Cytogenetic studies were performed at baseline in 64% of patients and fluorescence in situ hybridization (FISH) studies in 54%. Cytogenetics and FISH were normal in 27% of patients, while in 20% both were abnormal in patients who had both performed. FISH was abnormal with normal cytogenetics in 41% and only 2% had normal FISH but abnormal cytogenetics. The most common FISH abnormalities were: 13 q- (31%), 17 p- (28%), t(4; 14) (16%). Freelite® testing was performed in 56% of patients with an abnormal ratio in 94% [rFLC]. Of evaluable patients receiving frontline therapy 98% of patients received a novel agent and only 3 patients (1.4% of treated patients) received melphalan/prednisone. Two drug combinations were used in 53%, 3 drugs in 26%, 4 drugs in 1.3%, and single agents were used in 21% of the patients. The most common regimens were: bortezomib+dexamethasone (28%), lenalidomide+dexamethasone (20%), and bortezomib+lenalidomide+ dexamethasone (15%). Conclusion: These baseline features and treatment choices characterize myeloma patients primarily in community-based practices in the US in 2010. As academic centers enroll more patients, we will be able to further characterize that population. Of particular note, 26% of patients were asymptomatic at baseline but had biochemical evidence of myeloma and met enrollment criteria; conversely 95% had an abnormal rFLC and 73% had abnormal chromosome results. The Connect MM® registry will provide data regarding patient features as they pertain to patterns in testing and treatment in the clinical practice setting, as well as response and survival outcomes. Disclosures: Durie: Celgene & Millennium: Consultancy. Off Label Use: Revlimid (lenalidomide) in combination with dexamethasone is indicated for the treatment of multiple myeloma patients who have received at least one prior therapy. Shah:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Research Funding; Novartis: Research Funding. Abonour:Celgene & Millennium: Honoraria. Gasperetto:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Speakers Bureau. Mehta:Celgene: Consultancy, Speakers Bureau; Takeda/Millennium: Speakers Bureau; Onyx: Research Funding. Pashos:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding. Toomey:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Swern:Celgene: Employment. Street:Celgene: Employment. Sullivan:Celgene: Employment, Equity Ownership. Rifkin:Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Amgen: Speakers Bureau; Cephalon: Speakers Bureau; Dendreon: Speakers Bureau.

Meta-Analytic Summary of the Burden of Pain and Fatigue in Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5967-5967
Author(s):  
Peter C. Trask ◽  
Mark Atkinson ◽  
Bhumi Trivedi ◽  
Andrew Palsgrove ◽  
William Benton Jones ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Sensitivity Analysis ◽  
Research Funding ◽  
Meta Analysis ◽  
Clinical Group ◽  
Common Symptom ◽  
Newly Diagnosed ◽  
Eortc Qlq C30 ◽  
Eortc Qlq ◽  
The Impact

Abstract Aims: Multiple myeloma (MM) is a hematologic malignancy of plasma cells. Bone disease is a characteristic symptom of MM, and pain is one of its most distressing features. Anemia is also a common symptom and is manifested as fatigue and tiredness among MM patients. We conducted a systematic review and meta-analysis of the EORTC QLQ-C30 pain and fatigue scales in two clinical MM populations (one with newly-diagnosed MM and a second undergoing medical management with re-emergent or advanced myeloma) to more precisely quantify the burden of pain and fatigue in MM. Methods: Studies assessing pain and fatigue in MM were identified through a search of specific terms in the medical-subject headings and keywords in PubMed. Inclusion criteria were English-language studies published between January 1, 1996, and July 1, 2014; diagnosis of MM; and availability of data on pain and/or fatigue as measured by the EORTC QLQ-C30. Full-text articles from germane abstracts were retrieved for eligibility assessment, and 27 articles were selected for inclusion in the analysis. Two groups of peer-reviewed articles were created: one consisting of publications that focused on newly-diagnosed MM and the other consisting of articles involving MM patients with advanced conditions, including those who had a disease recurrence or were receiving autologous bone marrow transplantation. The mean values and standard deviations (SDs) were recorded across all publications irrespective of sex, age, and stage of illness. Of the 27 studies, 17 did not report standard error (SE) or SD values associated with EORTC QLQ-C30 pain and fatigue scales. These missing values were estimated using the overall average of SDs for that scale observed across all studies within the publication group (either newly-diagnosed or recurrent/advanced disease). A sensitivity analysis was conducted to compare the pooled mean and SEs associated with results obtained with and without the SD imputation procedure. The means and SDs from the two sets of publications were entered into Comprehensive Meta-analysis™ with both scales (pain or fatigue) and existing or imputed SDs as grouping variables. The summary means and confidence intervals for each scale by clinical group were computed by weighting the individual studies by sample size and were statistically summarized based on a fixed-effect model. Results: The EORTC QLQ-C30 fatigue and pain scales range from 0-100 with higher scores indicating greater symptoms (i.e., more fatigue and pain). The overall mean across the 27 publications was 47.1 for fatigue and 48.2 for pain for MM patients compared to scores of 25.0 and 16.9 for a general population. The results of the sensitivity analysis indicated that estimation of the SDs for those studies missing the statistic did not have a significant effect on the summary mean estimate. In most cases, the inclusion of additional means with estimated SDs reduced the summary SE estimate associated with the summary mean. Overall, the scores for fatigue and pain across research articles involving newly-diagnosed patients (fatigue=48.5 and pain=49.1) were statistically higher (indicating worse pain and fatigue) than among patients who were recurrent or receiving more aggressive treatments (fatigue=39.9 and pain=38.7). Conclusions: The burden of pain and fatigue in MM is substantial and is different between newly-diagnosed and more advanced MM patients. Pain and fatigue can be easily quantified using standardized health-related quality of life instruments. Pivotal clinical trials in MM need to assess the impact of novel treatments on pain and fatigue. Disclosures Trask: Sanofi: Employment. Atkinson:Sanofi: Research Funding. Trivedi:Sanofi: Research Funding. Palsgrove:Sanofi: Research Funding. Jones:Sanofi: Employment. McHorney:Sanofi: Research Funding.

Efficacy and Safety of Three Bortezomib-Based Combinations in Elderly, Newly Diagnosed Multiple Myeloma Patients: Results From All Randomized Patients in the Community-Based, Phase 3b UPFRONT Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 478-478 ◽  
Author(s):  
Ruben Niesvizky ◽  
Ian W. Flinn ◽  
Robert Rifkin ◽  
Nashat Gabrail ◽  
Veena Charu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Treatment Period ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Community Based ◽  
Advisory Committees ◽  
Equity Ownership ◽  
Grade 3

Abstract Abstract 478 Background: The US community-based, phase 3b randomized, open-label, multicenter UPFRONT trial compares the efficacy and safety of three bortezomib (VELCADE®, Vc)-based regimens, VcD (Vc-dexamethasone), VcTD (Vc-thalidomide-dexamethasone), and VcMP (Vc-melphalan-prednisone), followed by weekly Vc maintenance, in elderly, newly diagnosed, transplant-ineligible multiple myeloma (MM) patients. This is the first phase 3 study of VcD and VcTD in this patient population. Methods: Patients with symptomatic, measurable MM were randomized (1:1:1) to receive 49 weeks of therapy: 24 weeks (eight 21-day cycles) of induction with VcD, VcTD, or VcMP (VcD: Vc 1.3 mg/m2, days 1, 4, 8, 11; D 20 mg, days 1, 2, 4, 5, 8, 9, 11, 12 [cycles 1–4]), days 1, 2, 4, 5 [cycles 5–8]); VcTD: Vc as before; T 100 mg/day, days 1–21; D as before); VcMP: Vc as before; M 9 mg/m2 and P 60 mg/m2, days 1–4, every other cycle), followed by 25 weeks (five 35-day cycles) of maintenance with weekly Vc 1.6 mg/m2, days 1, 8, 15, 22. Patients in the VcTD arm received concomitant prophylaxis with aspirin, full-dose warfarin, or low-molecular weight heparin unless medically contraindicated. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall response rate (ORR), complete response (CR)/near CR (nCR) and very good partial response (VGPR) rates, overall survival (OS), and safety. Best confirmed responses were assessed by investigators per modified International Myeloma Working Group (IMWG) criteria. Adverse events (AEs) were graded by NCI-CTCAE v3.0. PFS and OS were estimated by Kaplan–Meier methodology. For the first time, we report results from the entire cohort of 502 randomized patients (VcD, n=168; VcTD, n=167; VcMP, n=167), who completed up to a maximum of 13 cycles of treatment. Results: Patients in the VcD, VcTD, and VcMP arms had a median age of 74.5, 73.0, and 72.0 years, respectively, and 71%, 62%, and 72% had ISS stage II/III disease. Patients received a median of 8 (VcD), 6 (VcTD), and 7 (VcMP) treatment cycles; 50%, 38%, and 42% of patients, respectively, received Vc maintenance. Response and safety data are summarized in the table. All three Vc-based induction regimens exhibited substantial activity, with ORR of 73% (VcD), 80% (VcTD), and 69% (VcMP) during the treatment period. After a median follow-up of 21.8 months, no significant difference in PFS was observed between the treatment arms; median PFS was 13.8 months (VcD), 14.7 months (VcTD), and 17.3 months (VcMP), respectively (Figure). 1-year OS estimates were 87.4% (VcD), 86.1% (VcTD), and 88.9% (VcMP). Rates of grade ≥3 AEs, serious AEs (SAEs), and discontinuations due to AEs during the treatment period were highest for the VcTD arm. The most common grade ≥3 AEs across all three arms during the treatment period were neuropathy peripheral (23%), fatigue (10%), and diarrhea (9%). Grade ≥3 pneumonia was reported in 10% (VcD), 6% (VcTD), and 6% (VcMP) of patients. AEs of deep vein thrombosis/pulmonary embolism were reported in 8% (VcD), 7% (VcTD), and 2% (VcMP) of patients. Compared with rates during induction, Vc maintenance produced little additional toxicity; across all three treatment arms, only 5% of patients experienced grade ≥3 peripheral neuropathy during cycles 9–13. One second primary malignancy (lung neoplasm) was reported in the VcMP arm. Conclusions: VcD, VcTD, and VcMP induction followed by weekly Vc maintenance produced similar activity in elderly, newly diagnosed, transplant-ineligible MM patients. Patients in the VcD doublet arm appear to have similar long-term outcomes to patients in the VcTD and VcMP triplet arms. Disclosures: Niesvizky: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Research Funding. Flinn:Millennium Pharmaceuticals, Inc.: Research Funding. Rifkin:Celgene: Speakers Bureau; Amgen: Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees; Millennium Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Charu:GSK: Research Funding; Celgene: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Bristol-Myers Squibb: Equity Ownership; Pfizer: Equity Ownership. Neuwirth:Millennium Pharmaceuticals, Inc.: Employment. Corzo:Millennium Pharmaceuticals, Inc.: Employment.

Impact of Renal Impairment (RI) on Outcomes after Treatment (Tx) with Lenalidomide and Low-Dose Dexamethasone (Rd) in Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts): First Trial Results

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2112-2112
Author(s):  
Meletios A. Dimopoulos ◽  
Matthew C Cheung ◽  
Murielle Roussel ◽  
Ting Liu ◽  
Barbara Gamberi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Board Of Directors ◽  
Normal Renal Function ◽  
Research Funding ◽  
Failure Time ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Risk Of Death ◽  
The Impact

Abstract Background: Approximately 20–40% of pts with NDMM present with RI, which is associated with a negative impact on survival (Rajkumar, 2005). In the pivotal phase 3 FIRST trial (median follow-up 37 months [mos]), continuous Rd improved progression-free survival (PFS) vs. melphalan-prednisone-thalidomide (MPT) in elderly NDMM pts by 28% (25.5 vs. 20.7 mos; HR = 0.72; P < 0.01) (Facon, Blood 2013). Although 121 pts receiving continuous Rd are still on Tx, the interim overall survival (OS) analysis showed a 22% reduction in the risk of death in favor of continuous Rd vs. MPT (HR = 0.78; P = 0.02). The present analysis was conducted to determine the impact of RI on PFS, OS, and time to 2nd antimyeloma Tx (AMT) as clinical study outcomes. Methods: Pts were randomized to 3 Tx arms: continuous Rd until progression (n = 535); Rd for 18 cycles (72 weeks) (Rd18; n = 541); or MPT for 12 cycles (72 weeks) (n = 547). Enrolled NDMM pts were categorized according to their renal function: 24% had normal renal function (creatinine clearance [CrCl] ≥ 80 mL/min), 44% presented with mild RI (≥ 50 and < 80 mL/min), 23% had moderate RI (≥ 30 and < 50 mL/min), and 9% had severe RI (< 30 mL/min). Pts requiring dialysis were excluded. Lenalidomide starting dose was 25 mg QD for pts with normal renal function or mild RI, 10 mg QD for moderate RI, and 15 mg QOD for severe RI. Melphalan dose was reduced by 50% in pts with moderate or severe RI. The primary endpoint was PFS (continuous Rd vs. MPT); secondary endpoints were OS, overall response rate, time to response, duration of response, time to Tx failure, time to 2nd AMT, health-related quality of life, safety, and improvement in renal function from baseline. Improvement in RI was defined as shifts from baseline to most extreme post-baseline value of the calculated CrCl as a measure of renal function during the active Tx (N = 1484). Results: A PFS benefit favored continuous Rd vs. MPT irrespective of the degree of renal function (Table 1): there was a benefit in pts with normal renal function (HR = 0.72 (0.51–1.02); P = 0.06), and better in pts with mild RI (HR = 0.79 (0.62–1.00); P = 0.05) and moderate RI (HR = 0.62 (0.45–0.85); P < 0.01). A PFS benefit was also seen with continuous Rd vs. Rd18 (a secondary comparison) in pts with mild RI and moderate RI (P < 0.01 for both). An interim OS benefit with continuous Rd vs. MPT was observed in most renal subgroups. Similar results were observed between Rd18 and MPT in terms of PFS or interim OS in any of the renal subgroups. Continuous Rd, compared with Rd18 or MPT, extended time to 2nd AMT in most renal groups except severe RI (CrCl < 30mL/min) (Table 2). Improvement in RI was observed more frequently in pts treated with continuous Rd than those with Rd18 or MPT: improvement of mild RI, 48%, 43%, and 48%, respectively; of moderate RI, 67% 61%, and 62%; and of severe RI, 64%, 59%, and 56%. Overall, < 5% of pts in any Tx group experienced a worsening in renal function status during Tx (continuous Rd 2.2%; Rd18 2.8%; MPT 2.7%). The most common grade 3–4 adverse events (AEs) for these Txs were anemia, neutropenia, thrombocytopenia, deep-vein thrombosis/pulmonary embolism (DVT/PE), and peripheral sensory neuropathy (Table 3). Tx discontinuation due to AEs increased in pts with moderate and severe RI, regardless of the type of Tx (Table 3). Conclusions: PFS, OS (at interim analysis), and time to 2nd AMT outcomes generally improved continuous Rd vs. Rd18 or MPT in transplant-ineligible NDMM pts with normal renal function, and in those with mild or moderate RI. The small number of pts in the severe RI group precluded a meaningful conclusion. Continuous Rd was generally well tolerated and renal function improved in the majority of pts during Tx with continuous Rd vs. Rd18 or MPT. Disclosures Dimopoulos: Celgene Corporation: Consultancy, Honoraria. Off Label Use: Lenalidomide used in newly diagnosed multiple myeloma patients. Roussel:Celgene: Consultancy, Lecture fees Other, Research Funding. van der Jagt:Celgene Corporation: Research Funding. Jaccard:Celgene Corporation: Honoraria, Research Funding. Tosikyan:Celgene: Consultancy. Karlin: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; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees. Bensinger:Celgene Corporation: Consultancy, Research Funding. Schots:Celgene: Research Funding. Chen:Celgene Corporation: Employment. Marek:Celgene Corporation: Employment, Equity Ownership. Ervin-Haynes:Celgene Corporation: Employment. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

scholarly journals Subcutaneous Versus Intravenous Bortezomib in Two Different Induction Therapies for Newly Diagnosed Multiple Myeloma – Subgroup Analysis from the GMMG-MM5 Trial

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3475-3475 ◽  
Author(s):  
Maximilian Merz ◽  
Hans Salwender ◽  
Mathias Hänel ◽  
Uta Bertsch ◽  
Christina Kunz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Research Funding ◽  
Group Iv ◽  
Route Of Administration ◽  
Prolonged Treatment ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
The Impact

Abstract Background: In patients with relapsed multiple myeloma (MM), Moreau and colleagues (Lancet Oncol, 2011) demonstrated that subcutaneous (SC) administration of bortezomib (BTZ) significantly reduced rates of adverse events (AE) compared to the intravenous (IV) formulation without loss of efficacy. Prospective data on SC BTZ in newly diagnosed MM are limited. We investigated the impact of SC versus IV BTZ in two different induction therapies for patients with newly diagnosed MM treated within the multicenter, prospective randomized MM5 trial of the German Myeloma Multicenter Group (GMMG). Methods: From 06/2010 until 11/2013, 604 patients were randomly assigned to receive 3 cycles of PAd (BTZ 1.3 mg/m2, days 1, 4, 8 and 11; Doxorubicin 9 mg/m2 IV, days 1-4; Dexamethasone 20 mg/d, orally, days 1-4, 9-12 and 17-20) or 3 cycles VCD (BTZ 1.3 mg/m2, days 1, 4, 8 and 11; Cyclophosphamide 900 mg/m2IV; day 1, Dexamethasone 40 mg/d, orally, days 1-2, 4-5, 8-9 and 11-12) for induction therapy. In the MM5 trial, induction therapy is followed by stem cell mobilization and harvest, high-dose therapy and Lenalidomide-based consolidation/maintenance therapy. Primary end points of the ongoing study are response to treatment after induction therapy and progression-free survival. Due to improved AE profile of SC compared to IV BTZ reported by Moreau, the administration of BTZ was changed from IV to SC in 02/2012. Therefore, we were able to perform an explorative analysis of 598 patients who received at least one dose of trial medication (PAd: n=150 IV / 140 SC; VCD: n=154 IV / 140 SC). 14 patients were excluded from the analysis because administration of BTZ was changed after start of induction therapy. We analyzed whether the route of administration influenced the applied cumulative BTZ dose, toxicity and efficacy of PAd and VCD. Results: The cumulative applied BTZ dose was significantly higher in patients treated with SC BTZ (PAd: 28.9 mg; VCD: 28.8 mg) compared to IV-treated patients (PAd: 27.6 mg; VCD: 27.9 mg; p = 0.007). Analysis of reported AEs associated to induction therapy revealed a significantly higher rate in patients treated with IV BTZ (65.1%) compared to SC-treated patients (55.7%, p = 0.02). AE > °II were reported more frequently in the IV group (IV: 52.0%; SC: 43.9%, p = 0.004). In detail, abnormal laboratory findings including leucopenia and thrombocytopenia (IV: 23.0%; SC: 16.4%, p = 0.05), metabolism and nutrition disorders (IV: 12.5%; SC: 5.4%, p = 0.004) and gastrointestinal disorders (IV: 9.9%; SC: 3.9%, p = 0.006) occurred more often in IV-treated patients. Analysis of peripheral neuropathy (PN) ≥ °II revealed no significant differences between IV and SC BTZ during the first two cycles of induction therapy (cycle 1: IV: 1.6%; SC: 2.5%; cycle 2: IV: 2.3%; SC: 3.6%) but PN occurred more often in IV-treated patients during the third cycle of induction therapy compared to the SC group (IV: 7.6%; SC: 1.8%, p = 0.001). Overall response rates (partial response or better) were not influenced by the route of administration in patients treated with PAd (IV: 72.7%; SC: 70.7%; p = 0.79) or VCD (IV: 77.9%; SC: 82.1%; p = 0.39). Analysis of the VCD arm showed that rates of VGPR or better were significantly higher in patients treated with IV BTZ compared to SC-treated patients (IV: 41.6%; SC: 28.6%, p = 0.02). Rates of VGPR or better were also higher for IV-treated patients in the PAd arm but did not reach statistical significance (IV: 36.7%; SC: 31.4%, p=0.39). Patient characteristics including baseline creatinine levels > 2 mg/dl, obesity or age at inclusion > 65 years did not influence efficacy of IV or SC BTZ in both arms. Conclusion: Last year we reported on the favorable toxicity profile and equal efficacy of VCD compared to PAd. With the current analysis we demonstrate that toxicity is further reduced with SC BTZ compared to IV. We therefore recommend VCD as induction therapy. However, we show for the first time a possible loss of efficacy in SC-treated patients. Therefore it remains unclear whether the reduced toxicity justifies the general application of SC BTZ in newly diagnosed, transplant-eligible patients or whether a prolonged treatment (4 x VCD SC) may reduce toxicity while achieving similar efficacy. Further studies are warranted since our results are partially in contrast with the previously presented data in relapsed MM and the ongoing MM5 trial was initially not designed to prospectively investigate the effect of SC or IV BTZ. Disclosures Salwender: 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; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Binding site: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Scheid:Celgene: Honoraria; Janssen: Honoraria. Mai:Janssen: Travel support Other. Hose:Novartis: Research Funding. Schmidt-Wolf:Janssen: Consultancy, Honoraria. Weisel:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Onyx: Consultancy, Honoraria; BMS: Consultancy; Noxxon: Consultancy. Duerig:Janssen: Consultancy, Honoraria; Celgene: Honoraria. Goldschmidt:Janssen-Cilag: Honoraria, Research Funding, Speakers Bureau; Polyphor: Research Funding; Celgene: Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Chugai: Research Funding, Speakers Bureau; Onyx: Consultancy, Speakers Bureau; Millenium: Consultancy, Speakers Bureau.

scholarly journals A Novel Approach to Risk Stratification in Multiple Myeloma Using ISS Stage and FISH

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1800-1800 ◽  
Author(s):  
Shaji K. Kumar ◽  
Patricia Greipp ◽  
Morie A Gertz ◽  
Angela Dispenzieri ◽  
Linda B Baughn ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Final Model ◽  
Survival Table ◽  
The Impact ◽  
1Q Gain

Background: A variety of risk factors have been described in multiple myeloma and current risk assessment incorporates ISS stage with specific FISH results and serum LDH (R-ISS). However, this model does not include all the current abnormalities described as prognostic for survival in multiple myeloma. Importantly, the impact of many of these high-risk abnormalities are not uniform. We examined if we can better integrate FISH results into a risk assessment tool to better predict the outcomes of newly diagnosed MM. Patients and methods: We studied a cohort of 1316 patients with FISH done within 6 months of diagnosis of MM, in whom results for commonly observed abnormalities were available. We specifically examined the individual impact of common translocations involving chromosome 14, MYC rearrangements, chromosome 1q gain (single or multiple duplication) and del13q/monosomy 13. A risk assessment system was developed, weighting each abnormality according to their Risk Ratio and integrating ISS stage and serum LDH into the final model construction. Overall survival was calculated from diagnosis, with those alive at last follow up being censored. Results: We first examined the impact of each of the above FISH abnormalities: 1) high risk translocations [t(4;14), t(14;16), or t(14,20)], 2) trisomies, 3) t(11;14), 4) MYCrearrangements, 5) del13q/monosomy 13, and 6) 1q gain . Each of the abnormalities, except for t(11;14), was prognostic for survival (Table 1 with the risk ratios). For 1q gain, the median OS was NR, 105 mos and 79 mos respectively for no abnormality, duplication of 1 copy and duplication of multiple copies, (p<0.001). On multivariate analysis, t(11;14) and trisomies were no longer prognostic for overall survival (Table 1). The cumulative impact of abnormalities demonstrated worsening survival in the presence of increasing numbers of abnormalities (Figure 1). Including ISS stage 3 and LDH > ULN as additional variables for prognostication indicated both were individually prognostic for OS. In a multivariate analysis, including these two and FISH abnormalities, 1q gain and LDH were not independently prognostic. The final model consisted of HR translocations, MYCrearrangements, del17p/monosomy 17, del13q/monosomy 13, and ISS stage 3. Each of these variables was weighted using their risk ratio and a composite score was developed using 998 patients for whom all variables were available (range: 0-7.9; median 1.8). Three patient groups were characterized: group 1 (0; 32%), group 2 (1-4; 58%) and group 3 (>4; 10%) with a median OS of 53 mos, 106 mos, and NR, respectively, p <0.001 (Figure 2). Conclusion: Using the most relevant FISH and laboratory factors, in a large cohort of patients, we refined the current system to develop a risk stratification system that predicts survival in patients with newly diagnosed MM treated with contemporary treatment regimens. This needs validation in future studies. Disclosures Kumar: Janssen: Consultancy, Research Funding; Takeda: Research Funding; Celgene: Consultancy, Research Funding. Gertz:International Waldenstrom Foundation: Research Funding; Annexon: Consultancy; Medscape: Consultancy, Speakers Bureau; Amyloidosis Foundation: Research Funding; Abbvie: Other: personal fees for Data Safety Monitoring board; i3Health: Other: Development of educational programs and materials; Springer Publishing: Patents & Royalties; Physicians Education Resource: Consultancy; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; Ionis/Akcea: Consultancy; Alnylam: Consultancy; Prothena Biosciences Inc: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Spectrum: Consultancy, Research Funding; Appellis: Consultancy; Research to Practice: Consultancy; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Amgen: Consultancy. Dispenzieri:Akcea: Consultancy; Janssen: Consultancy; Intellia: Consultancy; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Alnylam: Research Funding. Lacy:Celgene: Research Funding. Dingli:alexion: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Rigel: Consultancy; Karyopharm: Research Funding. Kapoor:Celgene: Honoraria; Janssen: Research Funding; Sanofi: Consultancy, Research Funding; Glaxo Smith Kline: Research Funding; Takeda: Honoraria, Research Funding; Amgen: Research Funding; Cellectar: Consultancy. Leung:Prothena: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Omeros: Research Funding; Aduro: Membership on an entity's Board of Directors or advisory committees. Bergsagel:Celgene: Consultancy; Ionis Pharmaceuticals: Consultancy; Janssen Pharmaceuticals: Consultancy.

scholarly journals Outcomes of Patients with Multiple Myeloma Harboring Gain/Amplification 1q in the Era of Modern Therapy

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 45-46
Author(s):  
Xiao Hu ◽  
Cherng-Horng Wu ◽  
Janet Cowan ◽  
Raymond L. Comenzo ◽  
Cindy Varga
Keyword(s):  
Multiple Myeloma ◽  
Survival Data ◽  
Research Funding ◽  
The United States ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Rank Tests ◽  
Treatment Regimens ◽  
The Impact ◽  
Log Rank Tests

Background: Multiple myeloma (MM) is the second most common hematological malignancy in the United States. Fluorescence in-situ hybridization (FISH) is a popular tool to detect cytogenetic alterations which in turn, can contribute to the risk stratification of patients with MM. Gain or amplification of CKS1B gene at chromosome 1q21 region (gain 1q) is detected in 35-40% of newly diagnosed MM cases, and has been reported to be associated with inferior prognostic outcomes. It also frequently occurs with the deletion of CDKN2C at chromosome 1p32.3 (del 1p). There is a distinct lack of data on patients harboring this cytogenetic alteration in the era of novel agents. We sought to look at outcomes of this patient population at a single institution over the last 5 years. Methods: This retrospective study included all patients with MM as defined by the International Myeloma Working Group (IMWG) with available FISH studies identifying gain 1q between 01/01/2015 to 04/30/2020 at Tufts Medical Center. The study was approved by the Institutional Review Board. Baseline demography, disease characteristics, and treatment history were extracted from the electronic medical records. With death as primary event, overall survival (OS) was defined as the survival time from the discovery of gain 1q to death. Progression free survival (PFS) was defined as the time from discovery of gain 1q to first progression/relapse or death, whichever occurred first. Kaplan-Meier method was used to estimate survival data. Differences in survival between two groups were analyzed by log-rank tests. Multivariable cox regression adjusting for baseline characteristics and significant concurrent cytogenetic alterations were performed to explore the impact of treatment regimens on survival. Results: Of the forty-nine subjects included in this study, the age range was 39 to 85 years; 31 patients (63.3%) were over the age of 65 years, and 28 (57.1%) were male. Twenty-eight (57.1%) subjects with gain 1q were newly diagnosed while the remaining 21 (42.9%) were identified at relapse. Gain 1q was present in more than 20% of clonal cells in 73.5% of subjects and 29.6% had del 1p as well. Patients with gain 1q were more likely to have deletion 13q (65.3%) and hyperdiploidy (61.2%). Regarding treatment, 75.7% of patients received bortezomib, 70.3% received lenalidomide, 38.9% underwent autologous stem cell transplant (ASCT) and 64.9% received daratumumab. At the time of analysis, 41 patients were still alive. For the entire cohort, the estimated median OS was not reached (NR) (95% confidence interval [CI], 24.1-NR), and the estimated median PFS was 15.27 months (95% CI, 4.77-NR). In log-rank tests, presence of extra medullary disease was associated with shorter PFS (4.8 vs 24.1 months, P=0.003), while IGH abnormalities including complex IGH rearrangements or losses were associated with longer PFS (NR vs 8.2 months, P=0.046). Lenalidomide-based treatment was associated with prolonged OS (NR vs 17.2 months, P=0.048). Bortezomib-based therapy and upfront ASCT were associated with improved PFS (15.3 vs 4.7 months, P=0.036; NR vs 4.8 months, P =0.019 respectively). Further multivariate analyses adjusting for age, number of CKS1B copies, International Staging System stage, baseline creatinine, clone size, del 1p, lactate dehydrogenase, extra medullary disease, and IGH abnormalities revealed that administration of daratumumab after the discovery of gain 1q was associated with superior OS (Hazard Ratio [HR]=0.023x10^-2, 95% CI [0.002x10^-4, 0.299], P =0.022) compared with those not receiving this agent; both the use of bortezomib (HR=0.210, 95% CI [0.064, 0.687], P =0.010) and daratumumab (HR=0.126, 95% CI [0.015, 1.036], P =0.054) were associated with prolonged PFS. The use of lenalidomide or upfront ASCT lost prognostic benefit after adjusting for additional variables in multivariate models. Conclusions: The outcomes of MM patients with gain 1q were evaluated according to clinical characteristics, concurrent chromosomal alterations and treatment regimens. In our small cohort, daratumumab and daratumumab-bortezomib combination regimens were found to have a favorable impact on survival. Future prospective clinical trials with larger sample sizes are warranted to confirm the results and further improve the outcomes of MM patients with this cytogenetic alteration. Disclosures Comenzo: Amgen: Consultancy; Takeda: Consultancy, Research Funding; Sanofi: Consultancy; Unum: Consultancy; Caleum: Consultancy; Prothena: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding.

Prolonged Follow-up Confirmed a Role for Upfront Tandem Auto-Allo Transplant in Multiple Myeloma Also in the Era of New Drugs

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3469-3469
Author(s):  
Luisa Giaccone ◽  
Andrea Evangelista ◽  
Francesca Patriarca ◽  
Roberto Sorasio ◽  
Massimo Pini ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Advisory Board ◽  
New Drugs ◽  
Main Concern ◽  
Newly Diagnosed ◽  
Post Transplant ◽  
The Impact

Abstract Introduction: Before the introduction of new drugs, we designed a trial where treatment of newly diagnosed multiple myeloma (MM) patients with double autografts or autograft followed by nonmyeloablative allograft was based on the presence or absence of HLA identical siblings (Bruno B et al. N Engl J Med 2007) We reported an update with special focus on long term outcomes. Methods: From September 1998 to July 2004, 162 consecutive patients with newly diagnosed MM up to the age of 65 years and at least one sibling were enrolled at 5 Italian centers, and divided into 2 groups: donor (N=80) vs no donor (N=82). First-line treatments consisted of a cytoreductive autograft followed by a HLA identical sibling nonmyeloablative allograft or a second melphalan-based autograft (N=58 and N=46, respectively, completed the protocol). Results: Median follow-up was 12.3 years (range, 7.7-15.3) from allograft, and 12.1 years (range, 10.5-15.4) from second autograft. The 5-year cumulative incidence of non-relapse mortality was 17.2% (95%CI: 7.4 to 27.1) in the allograft arm and 4.3% (95%CI:0 to 10.3) in the autograft arm. One of the main concern post allograft is the impact of chronic graft-versus-host disease (cGVHD): in our setting its 2-year cumulative incidence was 67.2% (95%CI: 54.9 to 79.5). We also evaluated the cumulative incidence of immunesuppression discontinuation in patients with cGVHD, considering both death and relapse as competing events: 26.8% of cGVHD patients (95%CI: 13 to 40.6) at 24 months and 39% (95%CI:23.6 to 54.4) at 60 months were alive and without therapy. Median overall survival (OS) and progression-free survival (PFS) from second transplant were 137 and 43 months in the allograft arm and 46 and 18 months in the autograft one (p=0.006 and p=0.001, respectively). In the allograft arm, 33 out of 58 patients relapsed at least once, and first salvage treatments included donor lymphocyte infusion (DLI, N=13), thalidomide (N=10) and bortezomib (N=8). Of note, 2 patients lost complete remission status but did not require further therapy. Nineteen out of 33 patients required a second post-transplant salvage treatment: 1 received chemotherapy, 1 DLI, 1 received debulking treatment with bortezomib followed by a second allograft, and 16 patients were treated with new drugs containing regimens. In the autograft arm, 36/46 patients relapsed and received salvage treatments consisting of: allograft (N=1), 3rd autograft prepared with a new-drugs containing regimen (N=6), thalidomide (N=17), bortezomib (N=7), lenalidomide (N=1), chemotherapy alone (N=4). Among these, 19 required a third-line treatment: 1 received an allograft, and 18 a regimen containing new drugs. Median OS from 1st relapse was 89.8 months (95%CI: 33.3 to n.r.) in the allograft arm vs 23.5 months (95%CI: 12.5 to 50.5) in the autograft (p=0.009). Conclusions: Our update showed that more then a third of patients developing cGVHD were relapse-free and cGVHD-free at 5-years post-transplant and that the advantage in OS in the allograft arm is maintained also after relapse, suggesting a synergism between graft-vs-myeloma effect and new agents. Upfront allograft in MM remains a matter of debate, and it should be performed only within clinical trials. The main limit of the present study was the lack of novel agents as part of the pre-transplant approach, nevertheless our results suggested that allograft may have a role, and it might be considered in young patients with high-risk features such as del [13], t(4;14), del(17p), and t(14;16), who remain at poor prognosis even in the era of new drugs. Disclosures Bringhen: Mundipharma: Other: ADVISORY BOARD; Amgen: Other: ADVISORY BOARD; Janssen-Cilag: Honoraria; Celgene: Honoraria; BMS: Honoraria; Karyopharm: Other: ADVISORY BOARD. Massaia:Janssen: Other: advisory board; Roche: Other: advisory board, research support; Gilead: Other: advisory board. Palumbo:Janssen Cilag: Honoraria; Takeda: Employment, Honoraria. Boccadoro:CELGENE: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; SANOFI: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Mundipharma: Research Funding; Abbivie: Honoraria; Novartis: Honoraria, Research Funding; Amgen: Honoraria, Research Funding.

scholarly journals Abnormal Metaphase Cytogenetics Adds to Currently Known Risk-Factors for Venous Thromboembolism in Multiple Myeloma: Derivation of the PRISM score

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-30
Author(s):  
Rajshekhar Chakraborty ◽  
Lisa Rybicki ◽  
Jason Valent ◽  
Alex V. Mejia Garcia ◽  
Beth M. Faiman ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
High Risk ◽  
Research Funding ◽  
Treatment Initiation ◽  
Newly Diagnosed ◽  
Prism Score ◽  
C Statistic ◽  
The Impact ◽  
Disease Specific

Background: Prevention and management of venous thromboembolic events [VTE] is an important component of supportive care in newly diagnosed multiple myeloma [MM], especially in the era of immunomodulatory drugs [IMiDs]. Recently, two validated risk assessment models [RAMs], SAVED and IMPEDE-VTE, were developed to identify patients at high risk of VTE. However, these models have following limitations: (1) Patients were not uniformly treated in the era of contemporary MM therapy (2) Disease-specific variables were not available in the databases from which these scores were derived. Our primary aim was to develop a simple predictive model for VTE in MM using patient-specific, disease-specific, and treatment-specific variables. Our secondary aim was to assess the impact of VTE on overall survival [OS]. Methods: All consecutive patients with newly diagnosed MM treated at Cleveland Clinic from 1/1/2008 to 12/31/2018 were included in our analysis. The primary objective was to identify baseline variables associated with VTE within 12 months of treatment initiation. Candidate variables included those in IMWG, SAVED, and IMPEDE-VTE models as well as additional risk-factors from literature review in MM and cancer-associated VTE. Stepwise selection with variable entry criterion of p&lt;0.20 and a variable retention criterion of p&lt;0.05 was used to identify significant factors on multivariable analysis [MVA]. RAM was developed by subtracting 1 from the hazard ratio of a potential variable, rounding to the nearest 0.5, and multiplying by 2 to obtain a whole number. The impact of VTE on OS was assessed with landmark analysis. Results: A total of 934 patients with newly diagnosed MM and available data on VTE occurrence were considered for inclusion. We excluded patients with VTE within 6 months before starting therapy [n=5] and patients on therapeutic anticoagulation or receiving &gt;1 prophylactic regimen [n=146], resulting in a total of 783 patients for model development. The most common induction regimen was bortezomib [V]-lenalidomide [R]-dexamethasone [VRD; 41%], followed by VD [22%], RD [20%], V-cyclophosphamide-dexamethasone [VCD; 11%], and others [7%]. Median age at treatment initiation was 63 years [range, 22-91], 55% were males, and 20% were Blacks. ISS stage III disease was present in 32%, high-risk FISH in 23%, abnormal metaphase cytogenetics in 18%, and serum creatinine &gt;2 mg/dl in 19% of patients. Notably, 76% had received a dexamethasone dose of 120-160 mg/cycle, with only 5.9% started on a higher dose [&gt;160 mg/cycle]. The most common thromboprophylaxis agent was aspirin [60%], followed by low molecular weight heparin [LMWH; 3.8%]; 37% of patients received no thromboprophylaxis. Erythropoietin and intravenous immunoglobulin were used in 2.9% and 1.2% of patients respectively. Median time to VTE from treatment initiation was 3.2 months. Cumulative incidence of VTE at 6 and 12 months was 8.2% [95% CI, 6.6-10.1] and 11.5% [95% CI, 9.5-13.6] respectively. Factors significantly associated with development of VTE on MVA were combined to develop the PRISM score [Table 1]: Prior VTE history [HR 5.06; 8 points], Black Race [HR 1.71; 1 point], IMiD use [HR 2.17; 2 points], Surgery within 3 months [HR 3.44; 5 points], and abnormal Metaphase cytogenetics [HR 2.10; 2 points]. The theoretical score range is 0-18, with a HR of 1.28 per 1-point increase in score [c-statistic 0.62]. Internal bootstrap validation including 1,000 samples showed a c-statistic of 0.62 [IQR, 0.60-0.64]. Using three risk groups by recursive partitioning analysis, 17.8%, 74%, and 8.1% belonged to low [0], intermediate [1-6], and high-risk [&gt;6] groups respectively. The 12-month cumulative incidence of VTE in the 3 respective groups were 2.7%, 10.8%, and 36.5% [Figure 1]. Occurrence of VTE in the first 12 months was not associated with worse OS on landmark analysis at 3, 6, 9, and 12 months. Conclusion: We have developed and internally validated a RAM for VTE in MM in the context of contemporary MM therapy including disease-specific variables. Studies of external validation and comparison with existing RAMs are warranted. The PRISM Score could be used to identify high-risk patients for thromboprophylaxis. Figure Disclosures Valent: Amgen Inc.: Other: Teaching, Speakers Bureau; Takeda Pharmaceuticals: Other: Teaching, Speakers Bureau; Celgene: Other: Teaching, Speakers Bureau. Khouri:Sanofi Genzyme: Other: Advisory Board. Anwer:Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau. Khorana:Pharmacyclics: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; Medscape: Honoraria; Leo Pharma: Honoraria; Seattle Genetics: Honoraria; Pharmacyte: Honoraria; Leap: Research Funding; Bayer: Honoraria; Janssen: Honoraria; Merck: Research Funding; Array: Other: Research funding (to institution); BMS: Honoraria, Research Funding.

Induction with New Drugs and Planned Autologous Followed by Non-Myeloablative Allogeneic Transplantation in Newly Diagnosed Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4330-4330
Author(s):  
Luisa Giaccone ◽  
Moreno Festuccia ◽  
Roberto Sorasio ◽  
Nicola Mordini ◽  
Fabrizio Carnevale Schianca ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Research Funding ◽  
Overall Response Rate ◽  
Response Rate ◽  
New Drugs ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Post Transplant ◽  
The Impact

Abstract Abstract 4330 Introduction Immunomodulatory drugs have recently changed the treatment options in multiple myeloma. Moreover, thalidomide, bortezomib and lenalidomide have also been used in the setting of allografting as post-transplant salvage therapy or as maintenance. We are currently evaluating the impact of new drugs as induction therapy in newly diagnosed multiple myeloma before a planned standard autograft followed by a non-myeloablative allograft (Tandem auto-allo). Patients and methods Twenty-five newly diagnosed patients (median age 55 years old, range 26-65) entered a recently designed prospective phase II program of tandem auto-allo which included the use of so-called new drugs during induction. Here, we report data on the first 11 evaluable patients with a follow up of at least 1 month after the allograft. Induction consisted of lenalidomide and dexamethasone (n=5), thalidomide and dexamethasone (n=4), or bortemomib-containing regimens (n=2), followed by G-CSF mobilized peripheral blood stem cell harvest. A standard autograft after melphalan 200 mg/m2 was planned 2-4 months before a low-dose (2 Gy) TBI-based allograft from an HLA-identical sibling. GVHD prophylaxis consisted of cyclosporin and mycophenolate mofetil. Disease status at allografting and post-transplant outcomes were compared to those of 22 patients pair-matched for beta2microglobulin and age, who underwent tandem auto-allo after induction with VAD-based regimens without new drugs (Blood, 2009). Results At the time of allografting after induction with new drugs and the autograft overall response rate was 81% (9/11), including a immunofixation-negative complete remission (CR). Following allografting, all patients promptly achieved donor engraftment. After a median follow-up of 11 months (2-26), all patients are alive and the overall response rate was 91% (10/11). Incidence of grade II-IV GVHD was 34% (4/11), including 1 patient with grade III GVHD. Chronic GVHD was observed in 40% (4/10) of patients with at least 3 months of follow-up. The induction with new drugs did not increase allotransplant-related toxicity or incidence of acute GVHD (Table 1). We observed a higher response disease before allografting in patients treated with new drugs. Conclusions Induction with lenalidomide, thalidomide or bortezomib does not impact feasibility and safety of tandem auto-allo. Longer follow up and a larger cohort of patients are necessary to evaluate the impact of new drugs in improving disease control post-tandem auto-allo. Disclosures: Patriarca: Janssen Cilag: Honoraria; Celgene: Honoraria. Boccadoro:Celgene: Consultancy, advisory committees, Research Funding; Pharmion: Consultancy, advisory committees, Research Funding; Janssen Cilag: Consultancy, advisory committees, Research Funding.

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