scholarly journals Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: A multicenter international myeloma working group study

Leukemia ◽  
2011 ◽  
Vol 26 (1) ◽  
pp. 149-157 ◽  
Author(s):  
S K Kumar ◽  
◽  
J H Lee ◽  
J J Lahuerta ◽  
G Morgan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Working Group ◽  
Risk Of Progression ◽  
International Myeloma Working Group

scholarly journals International Myeloma Working Group Recommendations for the Treatment of Multiple Myeloma–Related Bone Disease

2013 ◽  
Vol 31 (18) ◽  
pp. 2347-2357 ◽  
Author(s):  
Evangelos Terpos ◽  
Gareth Morgan ◽  
Meletios A. Dimopoulos ◽  
Matthew T. Drake ◽  
Suzanne Lentzsch ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Multiple Myeloma ◽  
Spinal Cord Compression ◽  
Bone Disease ◽  
Working Group ◽  
Cord Compression ◽  
Vertebral Compression Fractures ◽  
Bone Lesions ◽  
Published Data ◽  
International Myeloma Working Group

PurposeThe aim of the International Myeloma Working Group was to develop practice recommendations for the management of multiple myeloma (MM) –related bone disease.MethodologyAn interdisciplinary panel of clinical experts on MM and myeloma bone disease developed recommendations based on published data through August 2012. Expert consensus was used to propose additional recommendations in situations where there were insufficient published data. Levels of evidence and grades of recommendations were assigned and approved by panel members.RecommendationsBisphosphonates (BPs) should be considered in all patients with MM receiving first-line antimyeloma therapy, regardless of presence of osteolytic bone lesions on conventional radiography. However, it is unknown if BPs offer any advantage in patients with no bone disease assessed by magnetic resonance imaging or positron emission tomography/computed tomography. Intravenous (IV) zoledronic acid (ZOL) or pamidronate (PAM) is recommended for preventing skeletal-related events in patients with MM. ZOL is preferred over oral clodronate in newly diagnosed patients with MM because of its potential antimyeloma effects and survival benefits. BPs should be administered every 3 to 4 weeks IV during initial therapy. ZOL or PAM should be continued in patients with active disease and should be resumed after disease relapse, if discontinued in patients achieving complete or very good partial response. BPs are well tolerated, but preventive strategies must be instituted to avoid renal toxicity or osteonecrosis of the jaw. Kyphoplasty should be considered for symptomatic vertebral compression fractures. Low-dose radiation therapy can be used for palliation of uncontrolled pain, impending pathologic fracture, or spinal cord compression. Orthopedic consultation should be sought for long-bone fractures, spinal cord compression, and vertebral column instability.

scholarly journals New drugs and novel mechanisms of action in multiple myeloma in 2013: a report from the International Myeloma Working Group (IMWG)

Leukemia ◽  
2013 ◽  
Vol 28 (3) ◽  
pp. 525-542 ◽  
Author(s):  
E M Ocio ◽  
◽  
P G Richardson ◽  
S V Rajkumar ◽  
A Palumbo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Working Group ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
International Myeloma Working Group

scholarly journals Integrating Touchscreen-Based Geriatric Assessment and Frailty Screening for Adults with Multiple Myeloma to Drive Personalized Treatment Decisions

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3443-3443
Author(s):  
Nitya Nathwani ◽  
Supriya G. Mohile ◽  
Sandra Kurtin ◽  
Debra Wujcik ◽  
Susie Owenby ◽  
...  
Keyword(s):  
Older Adults ◽  
Multiple Myeloma ◽  
Geriatric Assessment ◽  
Working Group ◽  
Tumor Type ◽  
Frailty Status ◽  
Grade 3 ◽  
Line Of Therapy ◽  
Dose Modifications ◽  
International Myeloma Working Group

Background: Older adults with multiple myeloma (MM) may be at increased risk for toxicity of therapy. The International Myeloma Working Group (IMWG) frailty model, which includes age, functional status, and comorbidities, accounts for the presence of toxicity. The Cancer and Aging Research Group (CARG) Toxicity Tool (Hurria et al, JCO, 2011) includes more aging-associated domains and has been well validated in older adults with solid tumors, though not in hematologic malignancies. The association between the CARG toxicity tool and toxicity of therapy in older adults with MM is unknown. The parent study tested feasibility of an electronic modified geriatric assessment (mGA) tool providing real-time results to physicians. Methods: A retrospective chart abstraction was conducted on patients from the parent study to identify all treatments prior to the GA, time on treatment after enrollment, clinical data, treatment sequencing, incidence of Grade 3-5 toxicities, dose modifications, and treatment discontinuation or new line of therapy initiated. Patients were categorized as fit, intermediate fit or frail based on the IMWG score. The CARG score, adapted to apply to MM by removal of solid tumor type and use of the Modification of Diet in Renal Disease (MDRD) equation to calculate creatinine clearance, as recommended by the International Myeloma Working Group was calculated for each patient. Results: Data was available on 100 patients from the parent study. Average age was 71.3 ± 5.4 years, 58% Male, and 75% White. 71 individual regimens were identified with 575 incidences of use. Most patients were on their 4th line of therapy (mean=3.8 ± 2.9) and 22 were not receiving treatment at the time of the GA. Patients averaged 4.5 ± 3.7 lines of therapy and 46 patients underwent autologous stem cell transplants. Mean time on treatment for 78 patients after mGA was 27.2 weeks ± 28.4 weeks. CARG scores ranged from 0 to 17 with a mean of 5.9 + 7.8. mGA results were 35.7% (n=35) fit, 39.8% (n=39) intermediate fit, and 24.5% (n=24) frail using the IMWG frailty score. There was significant correlation between mean CARG scores and fit/frailty status (p<.000), with higher scores in frail patients. Hematological events after GA were common with 97% (n=97) reporting 1 or more > grade 3 events. Non hematologic events were less common with 38% (n=38) reporting 1 or more > grade 3 events. Incidences of hematologic and non-hematologic toxicities were not associated with CARG or IMWG frailty status. 44.9% (44 of 98) had dose modifications and 50% (49 of 98) had early therapy cessation. Conclusion: Older adults with MM are likely to require multiple lines of therapy over the course of their disease. Individualizing treatment and mitigating risk requires consistent application of geriatric assessment and toxicity tools. Our study did not find a significant association between the CARG toxicity tool, adapted for myeloma, or the IMWG frailty status. Future study will be needed to understand which patients were treated with initial dose reductions and how this impacted the risk of adverse events. Disclosures Wildes: Janssen: Research Funding; Carevive: Consultancy.

Overcoming the Interference of Daratumumab with Immunofixation Electrophoresis (IFE) Using an Industry-Developed Dira Test : Hydrashift 2/4 Daratumumab

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2063-2063 ◽  
Author(s):  
Helene Caillon ◽  
Alix Irimia ◽  
Jason S. Simon ◽  
Amy Axel ◽  
Kate Sasser ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Serum Protein ◽  
Working Group ◽  
Protein Electrophoresis ◽  
Globulin Fraction ◽  
M Spike ◽  
International Myeloma Working Group ◽  
Monoclonal Component

Abstract Background : Detection and quantification of monoclonal component (M-spike) by serum protein electrophoresis (SPE) and immunofixation (IFE) are essential for response evaluation in multiple myeloma (MM) according to the International Myeloma Working Group (IMWG) criteria. Recent clinical trials on daratumumab, an IgG Kappa anti-CD38 monoclonal antibody, have shown impressive results with deep responses. However daratumumab may be detected on serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for monitoring disease monoclonal immunoglobulins (M protein). This can lead to false positive SPE and IFE assay results for patients with IgG kappa myeloma protein impacting initial assessment of complete responses (CR) by International Myeloma Working Group (IMWG) criteria. Differentiating therapeutic monoclonal antibodies, such as daratumumab, from endogenous monoclonal protein can be challenging when both molecules co-migrate or migrate closely on electrophoresis. The availability of a specific, anti-daratumumab antibody has provided the opportunity to overcome this interference and to correctly assess biochemical response. Indeed, Mc Cudden and al. in collaboration with Janssen developed a technique, the Daratumumab Interference Reflex Assay (DIRA) test, which has been utilised in daratumumab clinical trials. Given the need for a commercially available automated and standardized test, we evaluated a new commercial DIRA kit test being developed by Sebia (Lisses, France): the Hydrashift 2/4 daratumumab. Objective: The aim of this study is to evaluate the Hydrashift 2/4 daratumumab in comparison with our laboratory developed DIRA test for the displacement of daratumumab on IFE. Design and methods: The Hydrashift 2/4 daratumumab assay was prepared by Sebia using the anti-daratumumab antibody produced by Janssen and modified to allow a migration of daratumumab/anti-daratumumab complexes toward the α-globulin fraction on IFE. IFE technical procedures, migration, and staining programs were performed according to the manufacturer instructions, and run on the standard Sebia, Hydrasys plateform, with the HYDRAGEL 4 IF kit. In addition to the regular procedure, an additional applicator to apply the anti-daratumumab antibody was used. Analytical performances including sensitivity, specificity and comparisons with the original DIRA test were assessed on 31 samples from ongoing daratumumab clinical trials. Results: Serum samples from 309/324 (95.4%) patients assessed demonstrated a positive IFE at diagnosis. In 119/309 (38,5%) of cases, the M-spike partially or totally co-migrated with daratumumab detected in serum. Of these, MM cases displayed an isotype other than IgG Kappa or Kappa light chains did not require a DIRA test during follow-up for response assessment as a standard IFE could clearly show if initial monoclonal component was still detectable or not. From our experience, an anti-daratumumab displacement assay was only required for IgG Kappa MM or Kappa Light Chain MM (LCMM) when standard IFE could not distinguish daratumumab from endogenous M-spike. This situation represented 66 cases (21,4 %, i.e. 66 on 309). The Hydrashift 2/4 daratumumab assay showed excellent concordance (100%) with the laboratory developed test on the 31 samples tested (i.e. 17 negative DIRA, 10 positive DIRA and 4 doubtful DIRA). Daratumumab/anti-daratumumab complexes were detected in the α-globulin fraction with a sensibility of 200 mg/L. Daratumumab/anti-daratumumab complex was difficult to visualize when daratumumab concentrations were less than 200 mg/L but daratumumab was shown to be completely removed from the gamma globulin fraction with no trace left for all tested patients. For 48 samples tested on diagnosis, the anti-daratumumab shifted specifically the daratumumab with no effect on the patients' M-spike (100% specificity). Conclusion: With the growing application of monoclonal antibodies such as daratumumab in the treatment of multiple myeloma, the development of validated, widely available assays to overcome antibody interference will become increasingly important. The Hydrashift 2/4 daratumumab test provides the opportunity to automate and standardize the displacement of daratumumab interference and help with the correct interpretation of IFE results for clinical outcome measures. Disclosures Simon: Janssen: Employment. Axel:Janssen Pharmaceuticals Research and Development: Employment. Sasser:Johnson & Johnson: Equity Ownership; Janssen Pharmaceuticals R&D: Employment. Scullion:Janssen: Employment. Ligneel:Sebia: Employment. Nouadje:Sebia: Employment. Moreau:Bristol-Myers Squibb: Honoraria; Amgen: Honoraria; Janssen: Honoraria, Speakers Bureau; Novartis: Honoraria; Takeda: Honoraria; Celgene: Honoraria.

Sign in / Sign up

Export Citation Format

Share Document