scholarly journals Screening for Monoclonal Gammopathy of Undetermined Significance: A Population-Based Randomized Clinical Trial. First Results from the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 156-156
Author(s):  
Sigurdur Y Kristinsson ◽  
Sæmundur Rögnvaldsson ◽  
Sigrun Thorsteinsdottir ◽  
Elin Ruth Reed ◽  
Jon Thorir Thorir Oskarsson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Binding Site ◽  
Monoclonal Gammopathy ◽  
Research Funding ◽  
Population Based ◽  
Advisory Committees ◽  
M Proteins ◽  
Screening Study

Abstract Background: Cancer screening is performed worldwide for several malignancies. Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM) and related lymphoproliferative disorders (LP). However, less than 5% of all MM patients are diagnosed during their precursor state and individuals who develop MM while being monitored for MGUS have better overall survival and fewer complications, compared to MM patients diagnosed without knowledge of MGUS. Thus, population-based screening for MGUS could identify candidates for early treatment of MM/LPs. To evaluate whether systematic screening is beneficial, we performed the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study, the first population-based screening study for MGUS that includes a randomized clinical trial (RCT) of follow-up and treatment strategies. Methods: All living residents of Iceland on September 9th, 2016 who were born before 1976 (N=148,708) were invited to participate. Of those, 80,759 (54.3%) provided informed consent for screening. Serum samples were collected from participants alongside clinical blood sampling in the Icelandic health service between September 2016 and the end of 2020. All samples were shipped to the Binding Site in Birmingham, UK, for screening. Samples were tested for M-proteins by capillary zone electrophoresis and immunofixation electrophoresis performed to confirm and characterize suspected M-proteins. Free light chains (FLCs) were measured using the FreeLite® assay. Individuals with a previous diagnosis of MM/LPs/MGUS (N=237) were excluded. Per protocol and informed consent, participants with MGUS were randomized to one of the three study arms: Arm 1 where participants are not contacted; Arm 2 where individuals are followed based on current guidelines; and Arm 3 where individuals are followed with a more intensive diagnostic and monitoring strategy. Participants who progress are offered early treatment. All participants repeatedly answered questionnaires on quality of life and mental health. Results: A total of 75,422 participants (93.4%) provided a serum sample for screening. Of those, 3,725 (4.9%) had MGUS. The prevalence of MGUS was dependent on age with 2.3%, 6.2%, and 12.9% diagnosed in age groups 40-59, 60-79, and 80-103 years, respectively. The prevalence of MGUS was higher in males, 5.9% vs 4.1% (p<0.0001). Most individuals with MGUS had either low-risk (38%) or low-intermediate (36%) risk MGUS, followed by high-intermediate (26%) risk MGUS. High-risk MGUS was only present in 0.2% of MGUS cases (n=9). The RCT includes 3,487 newly diagnosed MGUS individuals with 1164, 1159, and 1164 individuals in arms 1, 2 and 3, respectively (Table). The median age at diagnosis was 69 years in arms 1 and 2, and 70 years in arm 3. Females constituted 45.9% and the isotypes were IgG (50%), IgA (10%), IgM (18%) and biclonal (8%). The median M-protein concentration was 0.34 g/dL. A total of 428 light-chain MGUS cases were randomized. The demographic distribution was well balanced between the three arms. After a median follow-up of 3 years, 194 patients in the RCT have been diagnosed with any LP: 9 in arm 1, 92 in arm 2, and 133 in arm 3 (p<0.001). The participants in arm 1 were diagnosed with smoldering Waldenström's macroglobulinemia (SWM)(N=2), WM (N=2), chronic lymphocytic leukemia (CLL) (N=1), and MM (N=4). Participants in arm 2 were diagnosed with amyloidosis (N=1), SWM (N=18), WM (N=2), CLL (N=2), non-Hodgkin lymphoma (NHL) (N=1), smoldering MM (SMM) (N=56), and MM (N=12). Participants in arm 3 were diagnosed with amyloidosis (N=2), SWM (N=22), CLL (N=5), NHL (N=6), SMM (N=82), and MM (N=16). The difference between study arms was statistically significant for all LPs combined, and for SWM, SMM, and MM (Table). Conclusion: In this large prospective population-based screening study including >75,000 screened persons, we have identified 3,725 individuals with monoclonal gammopathy. In the RCT, after 3 years of follow-up, we show that active screening identifies significantly higher number of individuals with full-blown malignancy and smoldering disease, illustrating the fact that early detection and intervention is achievable. Although our findings are encouraging, until final results of the iStopMM study become available, including data on survival and quality of life, we advise against systematic MGUS screening in healthy individuals. Figure 1 Figure 1. Disclosures Kristinsson: Amgen: Research Funding; Celgene: Research Funding. Kampanis: The Binding Site: Current Employment. Hultcrantz: Curio Science LLC: Consultancy; Daiichi Sankyo: Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding; Intellisphere LLC: Consultancy. Durie: Amgen: Other: fees from non-CME/CE services ; Amgen, Celgene/Bristol-Myers Squibb, Janssen, and Takeda: Consultancy. Harding: The Binding Site: Current Employment, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Landgren: Janssen: Research Funding; Celgene: Research Funding; Janssen: Honoraria; Janssen: Other: IDMC; Amgen: Honoraria; Takeda: Other: IDMC; Amgen: Research Funding; GSK: Honoraria.

scholarly journals Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies

2021 ◽  
Vol 11 (5) ◽  
Author(s):  
Sæmundur Rögnvaldsson ◽  
Thorvardur Jon Love ◽  
Sigrun Thorsteinsdottir ◽  
Elín Ruth Reed ◽  
Jón Þórir Óskarsson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Early Treatment ◽  
Monoclonal Gammopathy ◽  
Controlled Trial ◽  
Participation Rate ◽  
Population Based ◽  
Early Therapy ◽  
Screening Study ◽  
Undetermined Significance

AbstractMonoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.

scholarly journals Preliminary Results of a Phase II Study of Lenalidomide-Elotuzumab As Maintenance Therapy Post-Autologous Stem Cell Transplant in Patients with Multiple Myeloma

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 840-840
Author(s):  
Sheeba K. Thomas ◽  
Jatin J. Shah ◽  
Hans C. Lee ◽  
Elisabet E. Manasanch ◽  
Donna M. Weber ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Maintenance Therapy ◽  
Board Of Directors ◽  
Research Funding ◽  
Advisory Committees ◽  
Best Response ◽  
Grade 3

Abstract Background: Lenalidomide (LEN) monotherapy has been effective in extending progression free survival (PFS) and after myeloablative AuSCT in patients (pts) with multiple myeloma (MM) (Attal et al. NEJM 2012, McCarthy et al. NEJM 2012,). Elotuzumab (ELO), a humanized IgG1 immunostimulatory monoclonal antibody against signaling lymphocytic activation molecule F7 (SLAMF7), is FDA approved in combination with LEN and dexamethasone (DEX) for treatment of pts with MM who have received 1-3 prior therapies. The objective of this phase 2 trial is to evaluate the efficacy and safety of adding ELO to LEN as maintenance therapy post-myeloablative AuSCT. We report preliminary results of the primary (PFS) and secondary (overall survival and toxicity) endpoints. Patients and Methods: Between 4/15/2015-1/27/2016, 28 evaluable pts were treated on 28 day cycles with ELO, 10 mg/kg iv weekly for cycles 1-2 and q2weeks for cycles 3-6, then 20 mg/kg once monthly for cycles 7+. Pts enrolled after 1/28/2016 (n=27 pts) have received ELO, 10 mg/kg IV weekly for cycles 1-2, and 20 mg/kg on day 1 from cycle 3 until progression. LEN has been dosed at 10 mg/day for cycles 1-3, with a dose increase to 15 mg/day at physician discretion starting with cycle 4, in the absence of non-hematologic toxicity > grade 1 and significant cytopenias (ANC < 1000/mL, platelet count < 100,000/ml). For the 1st 8 weeks, pts <75 yrs receive 28 mg of DEX 3-24 hours pre-infusion, while pts ≥75yrs receive 8mg; pts receive 4-10 mg iv DEX immediately pre-infusion for all cycles. Pts also receive herpes zoster prophylaxis and thromboprophylaxis commensurate with standard recommendations. The primary endpoint of the study is PFS, defined as the time from AuSCT to clinical progression or death (whichever occurs first), or the time of last contact. Secondary objectives include best response, overall survival, incidence of second primary malignancies and adverse event (AE) profile. Total enrollment of 100 pts is planned. Pts will be followed for 48 months after the last patient is enrolled in the trial. Eligible pts had received no more than 2 lines of induction therapy, and were between 60-210 days post-AuSCT. Results: Patients (n=55) have been treated for a median of 14 cycles (2-30). At study entry, 13 pts (24%) had complete response (CR), 27 (49%) had very good partial remission (VGPR), 14 (25%) had partial remission (PR) and 1 (2%) had minor remission (MR). Best response achieved to date on study is CR in 28 pts (51%), VGPR in 23 pts (42%) and PR in 4 pts (7%). For those who have converted to CR on study, median time to CR has been 5 months. Of 14 pts in CR who have been tested for MRD while on study, 13 are negative by flow cytometry (minimum of 2 million cells evaluated; sensitivity 10 -4-10-5). Two of these 13 have converted from VGPR to MRD negativity at 4 and 14 months on study, respectively. With a median follow up of 21 months, 95% of pts (n=52) remain alive. Three pts (all with high risk disease) had disease progression at 4 (del 17p), 9 (t [4;14]), and 13 (gain 1q) months; of these, 2 have died of progressive disease while receiving salvage therapy. One patient, in VGPR, died on study after developing acute cerebral encephalopathy with refractory status epilepticus of unclear etiology. Two pts withdrew for logistical reasons; 2 have been taken off study per physician discretion (prolonged cytopenias (1), drug rash (1)). Grade 3-4 Hematologic AEs (no. of pts) were: neutropenia 35% (16), thrombocytopenia 9% (4), febrile neutropenia 7% (3), and anemia 7% (3). Grade 3-4 non-Hematologic AEs (no. of pts): diarrhea 17% (8), fatigue 17% (8), pneumonia 15% (7), other infections 15% (7), peripheral neuropathy 11% (5), myalgias 9% (4), nausea/vomiting 7% (3), maculopapular rash 4% (2), dizziness 4% (2), edema 2% (1), memory impairment 2% (1). Renal cell carcinoma was diagnosed in 1 patient, 15 months after removal from study for disease progression. Conclusions: Lenalidomide-elotuzumab is a well-tolerated maintenance therapy on which 44% of 55 pts have had improvement in quality of response while on therapy, including 28% who have converted to CR and 24% who have tested MRD negative. The number of pts who have experienced improvement on study may, in fact, be underestimated in this analysis due to elotuzumab interference with measurement on electrophoretic studies. Additional follow up is required to determine if the improved quality of responses translate into improvements in PFS and OS. Disclosures Thomas: Bristol Myers Squibb: Research Funding; Celgene: Research Funding. Shah: Kayopharm: Employment. Lee: Pimera Inc: Consultancy; Eutropics Pharmaceuticals: Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Research Funding; Takeda: Consultancy; Celgene: Consultancy. Manasanch: merck: Research Funding; adaptive biotechnologies: Consultancy; sanofi: Research Funding; celgene: Consultancy; takeda: Consultancy; quest diagnostics: Research Funding. Patel: Juno: Consultancy; Celgene: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding. Orlowski: BioTheryX: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Monoclonal Gammopathy of Undetermined Significance and COVID-19: Results from the Population-Based Iceland Screens Treats or Prevents Multiple Myeloma Study (iStopMM)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 154-154
Author(s):  
Sæmundur Rögnvaldsson ◽  
Elias Eythorsson ◽  
Sigrun Thorsteinsdottir ◽  
Brynjar Vidarsson ◽  
Pall Torfi Onundarson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Hospital Admission ◽  
Board Of Directors ◽  
Monoclonal Gammopathy ◽  
Research Funding ◽  
Outpatient Visit ◽  
Large Population ◽  
Population Based ◽  
Composite Outcome ◽  
Advisory Committees

Abstract Introduction Multiple myeloma (MM) patients have an increased risk of severe coronavirus disease 2019 (COVID-19) when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Monoclonal gammopathy of undetermined significance (MGUS) precedes MM and related disorders and affects 4.2% of the general population over the age of 50 years. MM and MGUS are associated with immune dysfunction that is believed to contribute to the development of severe COVID-19. Currently, no systematic data on MGUS and COVID-19 have been published. We conducted a large population-based cohort study to evaluate whether MGUS was associated with SARS-CoV-2 infection and the development of severe COVID-19. Methods Data on all SARS-CoV-2 test results and COVID-19 severity was acquired from the COVID-19 Outpatient Clinic at Landspitali - The National University Hospital of Iceland. The first case of COVID-19 in Iceland was diagnosed on February 28 th, 2020. Since then, the Icelandic authorities have followed an aggressive strategy of SARS-CoV-2 testing and contact tracing. All SARS-CoV-2-positive individuals were immediately contacted and those with active infection were enrolled into telehealth monitoring consisting of repeated standardized interviews conducted by a nurse or physician. If clinical deterioration was detected, patients were assessed in person at the COVID-19 Outpatient Clinic and admitted if needed. Study participants were included from the Iceland Screens Treats or Prevents Multiple Myeloma study (iStopMM). The study is an ongoing population-based screening study for MGUS and randomized trial of follow-up strategies. Out of the 148,708 Icelanders who were born 1976 and earlier and were alive on September 9 th 2016, 80,759 (54%) provided informed consent for study participation and 75,422 (94%) of those provided a blood sample for MGUS screening by serum protein electrophoresis (SPEP) and free light chain (FLC) assay. MGUS was determined by current criteria using SPEP and FLC assay data. Individuals who had died, been diagnosed with MM and related disorders, or were undergoing treatment for smoldering MM prior to February 28 th were excluded. First, the association of MGUS and testing positive for SARS-CoV-2 was evaluated. We used a test negative design and included participants who had been tested at least once for SARS-CoV-2 between February 28 th and December 31 st, 2020. The association of MGUS and a positive test for SARS-CoV-2 was assessed using logistic regression, adjusted for sex and age. Next, the association of MGUS and severe COVID-19 was evaluated. Those who tested positive for SARS-CoV-2 were included unless they were hospitalized or living in a nursing home at diagnosis. Participants were followed until discharge from telehealth monitoring or until considered having severe COVID-19. Severe COVID-19 was defined as the composite outcome of the need for outpatient visit or hospital admission and death and as the composite outcome of hospital admission and death. Logistic regression was then performed adjusting for sex and age. Results Of the 75,422 individuals screened for MGUS, 32,047 (42%) were tested for SARS-CoV-2 during the study period of whom 1,754 had MGUS (5.5%). Those with MGUS were older (mean age 66.3 vs 59.1 p<0.001) and more likely to be male (50% vs 41% p<0.001). In total, 1,100 (3.4%) of the participants tested positive for SARS-CoV-2 of whom 65 had MGUS. After adjusting for sex and age, MGUS was not found to be associated with testing positive for SARS-CoV-2 (odds ratio (OR): 1.05; 95% confidence interval (CI): 0.81-1.36; p=0.72; Table; Figure A). Of those who tested positive for SARS-CoV-2, a total of 230 had the composite outcome of requiring an outpatient visit or hospital admission, and death, and 117 had the composite outcome of hospital admission and death. After adjusting for age and sex, MGUS was not found to be associated with either endpoint (OR: 0.99; 95%CI: 0.52-1.91; p=0.99 and OR: 1.13; 95%CI: 0.52-2.46; p=0.76; Table; Figure B) Conclusions: In this large population-based study that included 75,422 individuals screened for MGUS, we did not find MGUS to be associated with SARS-CoV-2 susceptibility or COVID-19 severity. This is contrary to MM which is preceded by MGUS. These findings suggest that immunosuppression in MGUS differs significantly from that of MM and are important since they can inform management and recommendations for individuals with MGUS. Figure 1 Figure 1. Disclosures Kampanis: The Binding Site: Current Employment. Hultcrantz: Intellisphere LLC: Consultancy; Daiichi Sankyo: Research Funding; Curio Science LLC: Consultancy; Amgen: Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Research Funding. Durie: Amgen, Celgene/Bristol-Myers Squibb, Janssen, and Takeda: Consultancy; Amgen: Other: fees from non-CME/CE services . Harding: The Binding Site: Current Employment, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Landgren: Amgen: Honoraria; Janssen: Honoraria; Celgene: Research Funding; Janssen: Other: IDMC; Janssen: Research Funding; Takeda: Other: IDMC; Amgen: Research Funding; GSK: Honoraria. Kristinsson: Amgen: Research Funding; Celgene: Research Funding.

scholarly journals Updated Health-Related Quality of Life Results from the KarMMa Clinical Study in Patients with Relapsed and Refractory Multiple Myeloma Treated with the B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T Cell Therapy Idecabtagene Vicleucel (ide-cel, bb2121)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2835-2835
Author(s):  
Michel Delforge ◽  
Nina Shah ◽  
Paula Rodríguez-Otero ◽  
Julia Braverman ◽  
Devender Dhanda ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Health Utility Index ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Meaningful Improvement

Abstract Introduction: Patients with heavily pretreated relapsed and refractory multiple myeloma (RRMM) have poor outcomes and poor health-related quality of life (HRQoL). The B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell therapy ide-cel has shown frequent, deep, and durable responses in patients with RRMM who were triple-class exposed (TCE) to immunomodulatory drugs, proteasome inhibitors (PI), and anti-CD38 monoclonal antibodies in the pivotal, phase 2, single-arm KarMMa trial (Munshi NC, et al. N Engl J Med 2021;384:705-716). Ide-cel is approved in the US by the FDA for the treatment of adults with RRMM after ≥ 4 prior lines of therapy, including an immunomodulatory drug, PI, and anti-CD38 monoclonal antibody. We have shown previously that in the KarMMa trial, ide-cel provides clinically meaningful benefits in HRQoL at 9 months' follow-up (Delforge M, et al. HemaSphere 2020;4(suppl 1). Abstract EP1000; Shah N, et al. Blood 2020;136(suppl 1):28-29). The aim of this analysis was to extend previous reports by analyzing the effect of ide-cel on HRQoL at 24 months post-infusion data cut off (December 21, 2020) in patients with TCE RRMM in the KarMMa trial. Methods: In the KarMMa trial (NCT03361748), eligible patients had ≥ 3 prior antimyeloma treatment regimens, were TCE, and refractory to their last treatment regimen per International Myeloma Working Group criteria. To assess HRQoL, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 (QLQ-C30), EORTC QLQ Multiple Myeloma Module (QLQ-MY20) and EuroQoL 5 dimensions 5 levels (EQ-5D-5L) questionnaires were administered at screening, baseline, at ide-cel infusion, at months 1-6, and every 3-6 months up to month 24 or end of study. Thresholds for clinically meaningful changes from baseline were predefined. Statistical significance was calculated using the 2-sided Wilcoxon signed rank test (0.05 significance level). Results: Of 128 patients treated with ide-cel, 126 (98%) had a baseline and ≥ 1 post-baseline HRQoL assessment and were included in the HRQoL-evaluable population. The patient questionnaire completion rate was ≥ 75% up to month 6 and 50%-70% thereafter for most visits. For the predefined primary HRQoL domains, mean scores improved after ide-cel treatment and were comparable to the general population (Table). Mean changes from baseline exceeded the minimal important difference (MID) threshold for clinically meaningful improvement in fatigue, pain, physical functioning, cognitive functioning, and global health status/quality of life (QoL) scores of QLQ-C30 and disease symptom scores of QLQ-MY20 through month 24 (data cutoff, December 21, 2020). Side effects of treatment (QLQ-MY20) remained stable. Overall, 40%-70% of patients had clinically meaningful improvements in the QLQ-C30 fatigue, pain, physical functioning, and global health status/QoL scores at later timepoints. Moreover, 30%-40% of patients experienced clinically meaningful improvements in cognitive functioning, disease symptoms, and side effects, with 40%-60% of patients remaining stable in these domains, across most of the post-baseline assessment visits. Predefined secondary HRQoL domains included all other domains from QLQ-C30 and -MY20, EQ-5D-5L health utility index scores, and EQ-5D visual analogue scale (VAS) scores. Mean changes from baseline exceeded the MID thresholds for clinically meaningful improvement and reached statistical significance across most follow-up visits for role functioning, emotional functioning, social functioning, dyspnea, insomnia, constipation, diarrhea (QLQ-C30), future perspectives (QLQ-MY20), health utility index scores (EQ-5D-5L), and VAS scores (EQ-5D). Mean changes from baseline for nausea/vomiting, appetite loss, financial difficulties (QLQ-C30), and body image (QLQ-MY20) scores were not clinically meaningful. At the individual level, most patients remained stable or achieved clinically meaningful improvements in secondary domains of interest across almost all follow-up visits. Conclusion: In this study, patients with TCE RRMM who received a single infusion of ide-cel showed clinically meaningful improvements across multiple HRQoL domains during the 24-month follow-up period. Figure 1 Figure 1. Disclosures Delforge: Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Shah: Sanofi: Consultancy; Sutro Biopharma: Research Funding; Janssen: Research Funding; Oncopeptides: Consultancy; Kite: Consultancy; Indapta Therapeutics: Consultancy; Poseida: Research Funding; Nektar: Research Funding; Precision Biosciences: Research Funding; Karyopharm: Consultancy; GSK: Consultancy; CareDx: Consultancy; BMS/Celgene: Research Funding; Bluebird Bio: Research Funding; CSL Behring: Consultancy; Amgen: Consultancy; Teneobio: Research Funding. Rodríguez-Otero: Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Oncopeptides: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy; Janssen, Celgene, Amgen, Oncopeptides, Sanofi, Abbvie, GlaxoSmithKline, Kite Pharma: Consultancy, Honoraria, Speakers Bureau; Regeneron: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Braverman: BMS: Current Employment, Current equity holder in publicly-traded company. Dhanda: BMS: Current Employment, Current equity holder in publicly-traded company. Shi: Bristol Myers Squibb: Consultancy. Guo: Bristol Myers Squibb: Consultancy; Daiichi Sankyo: Consultancy; UCB: Consultancy; Janssen: Consultancy; Gilead: Consultancy; EMD Serono: Consultancy; Evidera: Current Employment. Yu: Evidera: Current Employment. Liao: Evidera: Current Employment. Campbell: Bristol Myers Squibb: Current Employment, Current holder of individual stocks in a privately-held company. Munshi: Legend: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy; Abbvie: Consultancy; Pfizer: Consultancy; Adaptive Biotechnology: Consultancy; Novartis: Consultancy; Oncopep: Consultancy, Current equity holder in publicly-traded company, Other: scientific founder, Patents & Royalties; Takeda: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Bristol-Myers Squibb: Consultancy.

scholarly journals Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study

Blood ◽  
2009 ◽  
Vol 113 (22) ◽  
pp. 5412-5417 ◽  
Author(s):  
Ola Landgren ◽  
Robert A. Kyle ◽  
Ruth M. Pfeiffer ◽  
Jerry A. Katzmann ◽  
Neil E. Caporaso ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Population Based ◽  
Serum Samples ◽  
M Proteins ◽  
Cancer Screening Trial ◽  
Risk Of Progression ◽  
Study Population ◽  
A Prospective Study ◽  
Undetermined Significance

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma-cell proliferative disorder associated with a life-long risk of progression to multiple myeloma (MM). It is not known whether MM is always preceded by a premalignant asymptomatic MGUS stage. Among 77 469 healthy adults enrolled in the nationwide population-based prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, we identified 71 subjects who developed MM during the course of the study in whom serially collected (up to 6) prediagnostic serum samples obtained 2 to 9.8 years prior to MM diagnosis were available. Using assays for monoclonal (M)–proteins (electrophoresis/immunofixation) and kappa-lambda free light chains (FLCs), we determined longitudinally the prevalence of MGUS and characterized patterns of monoclonal immunoglobulin abnormalities prior to MM diagnosis. MGUS was present in 100.0% (87.2%-100.0%), 98.3% (90.8%-100.0%), 97.9% (88.9%-100.0%), 94.6% (81.8%-99.3%), 100.0% (86.3%-100.0%), 93.3% (68.1%-99.8%), and 82.4% (56.6%-96.2%) at 2, 3, 4, 5, 6, 7, and 8+ years prior to MM diagnosis, respectively. In approximately half the study population, the M-protein concentration and involved FLC-ratio levels showed a yearly increase prior to MM diagnosis. In the present study, an asymptomatic MGUS stage consistently preceded MM. Novel molecular markers are needed to better predict progression to MM in patients with MGUS.

Healthcare Resource Utilization Trends over Time with Continuous Lenalidomide Treatment (Tx) in Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1326-1326
Author(s):  
Katja Weisel ◽  
Dan T. Vogl ◽  
Michel Delforge ◽  
Kevin Song ◽  
Meletios Dimopoulos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Resource Utilization ◽  
Research Funding ◽  
Healthcare Resource ◽  
Healthcare Resource Utilization ◽  
Medical Utilization ◽  
Fixed Duration ◽  
Advisory Committees ◽  
Over Time

Abstract Introduction: Multiple myeloma (MM) is an incurable hematologic condition that is associated with high Tx costs. Resource consumption is driven by hospitalization and medical utilization, which is highest during periods of uncontrolled disease, such as after diagnosis and during relapses (De Portu 2013). In the pivotal phase 3 FIRST trial, continuous Tx with lenalidomide plus low-dose dexamethasone (Rd) was compared with fixed-duration Rd (Rd18) or fixed-duration combination Tx with melphalan, prednisone, and thalidomide (MPT), each for 18 months (mos), in NDMM pts who were ineligible for stem cell transplantation. Continuous Rd extended progression-free survival (PFS) and overall survival (interim analysis) vs. MPT. However, it is still unclear whether extending Tx duration with Rd adversely affects healthcare resource utilization. This analysis quantifies the rates of hospitalizations and medical utilization with continuous Rd over time based on data collected in the FIRST trial. Methods: The FIRST trial (N = 1,623) was a pivotal multinational, randomized, open-label study with a median follow up of 37 mos. Non-protocol-driven resource-use data was collected until subjects discontinued study Tx. To assess whether continuous Rd increases healthcare resource utilization over time, the rates of resource utilization for subjects treated with continuous Rd (N = 535) were plotted for up to 48 mos. In addition, hospitalization and medical utilization rates during the Tx period (18 mos) were estimated and compared between the 2 fixed-duration Tx arms. Results: Resource utilization amongst pts treated with continuous Rd declined over time (Figure). The annualized hospitalization rate in the first 3 mos was 3.2 times higher than the average rate for the remaining 45 mos of follow-up (2.02 vs. 0.62), and 4.2 times higher for medical utilization (5.66 vs. 1.34). After 4 years (yrs) of continuous Rd Tx, hospitalization and medical utilization rates were estimated to be 83% and 84% lower than those observed in the first 3 mos of Tx, reflecting the long-term disease control observed with continuous Rd in the FIRST trial. The highest hospitalization rates were associated with infections (0.20 per patient year), cardiovascular disorders (0.06), and respiratory and thoracic disorders (0.05). The mean (standard deviation) length of stay per admission was 14.08 (21.19) days. The highest medical utilization rates were associated with blood transfusions (0.76 interventions per patient year), general imaging procedures (0.21), respiratory and thoracic imaging procedures (0.20), and therapeutic interventions (0.09).The hospitalization rates for the fixed dose Tx arms were 0.91 (Rd18) and 0.79 (MPT) per patient year of follow-up during the Tx period of 18 mos, resulting in a rate ratio (RR) of 1.15 (1.01–1.30). The equivalent rates for medical utilization were 3.00 (Rd18) and 2.86 (MPT) medical interventions per patient year (RR = 1.05 [0.98–1.12]). Conclusions: The rates of resource utilization among pts treated with continuous Rd dropped substantially after the first 3 mos of Tx, and then gradually declined as Tx duration increased. The findings suggest that continuous Tx with Rd does not further increase resource utilization in hospitalizations and medical utilization compared to fixed-duration Tx. A comparison between the 2 fixed arms showed a 15% increase in hospitalization with Rd18 vs. MPT, and no differences in medical utilization between the 2 arms. A limitation of this analysis is that the resources were collected only while pts were receiving their respective Txs. Future analysis should include all costs generated by healthcare resources throughout pts Tx, including Tx-free intervals, and the costs associated with relapses. Figure 1: Hospitalization and medical utilization rates per patient year for patients treated with continuous Rd Figure 1:. Hospitalization and medical utilization rates per patient year for patients treated with continuous Rd Disclosures Weisel: BMS: Consultancy; Onyx: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene Corporation: Consultancy, Honoraria; Noxxon: Consultancy. Off Label Use: Lenalidomide used in newly diagnosed multiple myeloma patients. Vogl:Amgen: Consultancy; Millennium/Takeda: Research Funding; GSK: Research Funding; Acetylon: Research Funding; Celgene Corporation: Consultancy. Delforge:Janssen: Honoraria; Celgene Corporation: Honoraria. Song:Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Dimopoulos:Celgene Corporation: Consultancy, Honoraria. Cavenagh:Celgene Corporation: Honoraria. Hulin:Celgene Corporation: Honoraria. Foá:Celgene Corporation: Consultancy. Oriol:Janssen: Consultancy, Speakers Bureau; Celgene Corporation: Consultancy, Speakers Bureau. Guo:Celgene Corporation: Consultancy. Monzini:Celgene Corporation: Employment, Equity Ownership. Van Oostendorp:Celgene: Employment. Ervin-Haynes:Celgene: Employment. Facon:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Clinical Outcomes of Patients with Newly Diagnosed Multiple Myeloma Receiving Triplet Therapy in the Connect MM® Disease Registry

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4229-4229
Author(s):  
Jatin J. Shah ◽  
Rafat Abonour ◽  
Mohit Narang ◽  
Jayesh Mehta ◽  
Howard R. Terebelo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Advisory Committees ◽  
Risk Of Death ◽  
Equity Ownership ◽  
Triplet Regimen

Abstract Introduction: Triplet therapies are used for treatment (Tx) of both transplant-eligible and -ineligible patients (pts) with newly diagnosed multiple myeloma (NDMM). Actual patterns and outcomes of Tx are not fully understood. Connect MM® is the first and largest multicenter, US-based, prospective observational cohort study designed to characterize Tx patterns and outcomes for pts with NDMM. This analysis describes demographic and disease characteristics of pts who received triplet Tx as an induction regimen and for whom transplant was or was not intended. The analysis explores the relationship of these factors with overall survival (OS) and other efficacy endpoints. Patients and Methods: Pts aged ≥ 18 y with NDMM within 60 days of diagnosis were eligible for enrollment regardless of disease severity, medical history, or comorbidities. Data including transplant intent (yes/no) was collected at baseline; follow-up data was collected quarterly thereafter. Based on the initial intent, 2 groups were identified: patients with intent to transplant who received transplant (TT) and pts with no intent to transplant who did not receive a transplant (NT). Triplet Tx was defined as the combination of ≥ 3 concurrent therapeutic agents in the first course of Tx (within 56 days of study entry). KM analysis adjusted for age was conducted for OS. Because decisions on use of transplant and triplet therapy are influenced by multiple factors, a multivariable Cox regression analysis was performed to evaluate the contribution of the triplet therapy (yes/no) to OS and was adjusted for other variables, including age, comorbidities, and ISS staging. Results: Between September 2009 and December 2011, 1493 pts were enrolled. This analysis was on 1436 pts: 650 pts with transplant intent and 786 pts without transplant intent. The data cutoff date was November 30, 2014, and the median follow-up for overall survival (OS) was 33.8 mos. Of pts with transplant intent, 451 (69%) received transplant (TT) and 199 (31%) did not. Of pts without transplant intent, 62 (8%) received transplant and 724 (92%) did not (NT). The abstract focuses on TT and NT groups only. NT pts tended to be older and have more advanced ISS staging and higher β2-microglobulin levels than TT pts (Table). The most common triplet regimen given during the first course treatment (within 56 days) was lenalidomide, bortezomib, and dexamethasone (RVd). RVd was administered to 34% of the NT pts (76/225) and 59% of the TT pts (152/257). The most common non-triplet regimen was bortezomib and dexamethasone (Vd), which was given to 31% of NT pts (156/499) and 38% of TT pts (73/194). Within the NT group, pts given triplet Tx had a lower risk of death than those who did not receive triplet Tx (P = .0013). The multivariable analysis found triplet Tx to be associated with a 36% reduced risk of death (hazard ratio [HR] = 0.64 [95% CI, 0.50-0.82]; P = .001). ISS disease stage (HR = 1.43 [95% CI, 1.21-1.69]; P < .001) and history of diabetes (HR = 1.38 [95% CI, 1.08-1.78]; P = .012) were negative prognostic factors for OS. Within the TT group, pts who received triplet Tx did not attain an OS benefit (P = .8993), and no baseline characteristics were significantly associated with OS. These results may be limited by other factors not considered that may have influenced physicians' choice of treatment, including the use of maintenance therapy and a short follow-up period of 33.8 months. Conclusions: Triplet Tx as a first regimen is associated with longer OS in pts without transplant intent who did not receive a transplant. RVd and Vd were the most common first Tx regimens, respectively. Continued follow-up of these pts and enrollment of an additional cohort will provide additional data with mature follow-up. Table 1. Table 1. Disclosures Shah: Bristol-Myers Squibb: Research Funding; Array: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees. Abonour:Celgene: Research Funding, Speakers Bureau. Narang:Celgene: Speakers Bureau. Mehta:Celgene Corporation: Speakers Bureau. Terebelo:Millenium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacylics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Gasparetto:Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Honoraria, Other: Export Board Committee, Speakers Bureau. Toomey:Celgene: Consultancy. Hardin:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Srinivasan:Celgene Corporation: Employment, Equity Ownership. Larkins:Celgene Corporation: Employment, Equity Ownership. Nagarwala:Celgene Corporation: Employment, Equity Ownership. Rifkin:Onyx Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Updated Outcomes of Fludarabine/Melphalan/Bortezomib (Flu/Mel/Vel) Conditioning for Upfront Allogeneic Hematopoietic Cell Transplantation in Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5885-5885
Author(s):  
Taiga Nishihori ◽  
Claudio Anasetti ◽  
Rachid Baz ◽  
Jose L Ochoa-Bayona ◽  
Kenneth H. Shain ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Advisory Committees ◽  
Allogeneic Hct ◽  
Genetics Research ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors

Abstract Background: Multiple myeloma remains incurable despite impressive array of available novel agents and therapeutic strategies. Allogeneic hematopoietic cell transplantation (HCT) remains the only potentially curative option for patients with multiple myeloma but it is limited by its toxicities. We previously reported initial result of a phase 2 study of upfront allogeneic HCT in myeloma patients achieving at least very good partial response (VGPR) after initial therapy (Nishihori, et al. ASH 2013 abstract 3390) and here we report more mature results after a median follow up of 3 years. Methods: Twenty seven myeloma patients received allogeneic HCT between 01/2010 and 02/2015 at Moffitt Cancer Center (NCT 00948922). Eligible patients were age ≤ 60, achieving first ≥ VGPR or complete response (CR), and have 8/8 HLA-matched related or unrelated donors. Conditioning regimen consisted of fludarabine 30 mg/m2 for 4 days (days -6, -5, -4, and -3) and melphalan 70 mg/m2 for 2 days (days -4 and -3) followed by a single dose of bortezomib 1.3 mg/m2 on day -3 (Flu/Mel/Vel regimen). GVHD prophylaxis was initially left to the discretion of physicians but later modified to only tacrolimus/methotrexate. No maintenance therapy was prescribed after allogeneic HCT. Results: The median age at transplant was 50 (range, 25-58) years. Disease status at the time of allogeneic HCT was VGPR (n=17: 63%) and CR/stringent CR (n=10: 37%). All patients received unmanipulated peripheral blood stem cell grafts from HLA-matched related donors (n=14) or HLA-matched unrelated donors (n=13). Graft-versus-host disease (GVHD) prophylaxis was tacrolimus plus either methotrexate (n=19: 70%), or mycophenolate mofetil (n=4), or sirolimus (n=4). All patients achieved neutrophil engraftment with a median of 15 (range, 11-19) days. Platelet engraftment was achieved with a median of 17 (range, 13 - 35) days and 2 patients did not recover platelets. The cumulative incidences of grades II-IV and grades III-IV acute GVHD at day 100 were 63.6% (95% confidence interval (CI): 43.1-81.1) and 19.6% (95%CI: 5.4-39.9), respectively. The cumulative incidence of moderate to severe chronic GVHD was 56.4% (95%CI: 36.3-75.5) at 1-year. The cumulative incidences of transplant-related mortality at day 100, 1 year and 2 years were 7.4% (95%CI: 0.8-20.0), 11.1% (95%CI: 2.7-25.4), and 11.1% (95%CI: 2.7-25.4), respectively. Progression-free survival estimates at 1, 2, and 3 years were 74.1% (95%CI: 53.2-86.7), 65.1% (95%CI: 43.3-80.2), and 65.1% (95%CI: 49.9-87.5), respectively. With a median follow up of 39 months for surviving patients, overall survival estimates at 1, 2 and 3 years were 85% (95%CI: 64.9-94.1), 75.4% (95%CI: 52.6-88.3), and 69.1% (95%CI: 53.8-93.5), respectively. Conclusions: The results of the this phase 2 trial of upfront allogeneic HCT with fludarabine/melphalan/bortezomib (Flu/Mel/Vel) conditioning are promising and provide the rationale for reasonable potentially curative option to younger and fit patients who are eligible for upfront intensive consolidation strategy. This approach may be potentially valuable for those with high-risk myeloma and a multicenter study is currently being conducted (BMT CTN protocol 1302:NCT02440464). Disclosures Nishihori: Novartis: Research Funding; Signal Genetics: Research Funding. Baz:Takeda/Millennium: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Novartis: Research Funding; Karyopharm: Research Funding; Bristol-Myers Squibb: Research Funding; Signal Genetics: Research Funding. Shain:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen/Onyx: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Signal Genetics: Research Funding; Takeda/Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau. Alsina:Signal Genetics: Consultancy; Novartis: Research Funding; Takeda/Millennium: Research Funding; Amgen/Onyx: Consultancy, Speakers Bureau.

scholarly journals Real-World Outcomes for Standard-of-Care Treatments in Patients with Relapsed/Refractory Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4075-4075
Author(s):  
Michel Delforge ◽  
Marie-Christiane Vekemans ◽  
Sébastien Anguille ◽  
Julien Depaus ◽  
Nathalie Meuleman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
Retrospective Chart Review ◽  
Standard Of Care ◽  
Real World Data ◽  
Advisory Committees ◽  
Treatment Regimens

Abstract Background: With the advent of immunomodulatory agents (IMiDs), proteasome inhibitors (PIs) and, more recently, anti-CD38 monoclonal antibodies (mAbs), prognosis of patients with multiple myeloma (MM) has improved considerably. Unfortunately, even with these 3 major MM drug classes, most patients ultimately relapse and require further therapy. There remains an incomplete understanding of how patients who have received extensive therapy and with relapsed/refractory multiple myeloma (RRMM) are treated in routine clinical practice, as no standard-of-care exists for these patients, and what the outcomes are in this real-world setting. Objective: This study aims to evaluate the outcomes of patients with triple-class (IMiD, PI and anti-CD38 mAb) and triple-line exposed RRMM using real-world data from patients in Belgium. Methods: A multicenter, observational study, involving 7 non-academic and academic Belgian centers, was conducted based on a retrospective chart review of adult RRMM patients who started subsequent treatment from March 2017 through May 2021 after having received ≥3 lines of therapy including at least an IMiD, a PI, and anti-CD38-directed therapy (tri-exposed). Data were captured in an electronic case report form (Castor EDC). Patients with an ECOG performance status of ≥2, who received prior CAR-T treatment or prior BCMA-targeted therapy, or with a known active or prior history of CNS involvement (or with clinical signs thereof), were excluded. All treatment lines initiated after becoming eligible were used in the analysis. Specifically, all treatment lines for patients meeting the eligibility criteria more than once in their entire follow-up were included as separate observations, with date of treatment initiation as specific baseline for each treatment line. Cox proportional hazards models were fitted to explore the prognostic value with Overall Survival (OS), Progression Free Survival (PFS), and Time to Next Therapy (TTNT). Results: A total of 112 patients with 237 eligible treatment lines were included in the analysis; median follow-up was 16.6 months. In 45% of the initiated treatment lines, patients were refractory to 4 or 5 therapies, 62% had received ≥5 prior lines, 22% had extramedullary disease and in 48% of observations the time to progression in prior line was shorter than 4 months. After patients became tri-exposed, more than 50 unique treatment regimens were initiated, with the following being the most common: carfilzomib + dexamethasone (14%), pomalidomide + dexamethasone + chemotherapy (8%), and ixazomib + lenalidomide + dexamethasone (6%). Additionally, 4% of included observations were exposed to anti-BCMA agents. Overall, the following treatment classes were the most frequently started: PI only (19%), PI + IMiD combinations (17%), and regimens including anti-CD38 antibodies (15%). Median OS was 9.79 months [95% CI: 7.79; 12.22], median PFS was 3.42 months [95% CI: 2.79; 4.27], median TTNT was 3.61 months [95% CI: 3.09; 4.57]. Higher refractory status (p&lt;0.001), being male (p=0.001), older age (p&lt;0.001), shorter duration of prior lines (p&lt;0.001), shorter time to progression in prior line (p=0.025), and higher LDH levels (p&lt;0.002) were prognostic for worse outcomes for both OS (Figure 1) and PFS. Conclusions: This retrospective chart review of patients with tri-exposed RRMM in Belgium shows that real-world outcomes in terms of OS, PFS and TTNT are poor for these patients, with a median OS of &lt;10 months. A wide variety of treatment regimens used in clinical practice confirm the absence of a clear standard-of-care in this patient population. The literature also confirms that these poor outcomes observed in Belgium, for this subset of MM patients, are similar in other countries. These real-world data highlight the high unmet medical need in this patient population and critical need for new and effective treatment options. MD and MCV contributed equally to this work. Figure 1 Figure 1. Disclosures Delforge: Amgen, Celgene, Janssen, Sanofi: Honoraria, Research Funding. Vekemans: Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS-Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Pharmaceutica: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees. Depaus: Takeda: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Celgene: Consultancy. Meuleman: iTeos Therapeutics: Consultancy. Strens: Realidad bvba: Consultancy. Van Hoorenbeeck: Janssen: Current Employment. Moorkens: Janssen-Cilag: Current Employment. Diels: Janssen: Current Employment. Ghilotti: Janssen-Cilag SpA, Cologno Monzese, Italy: Current Employment. Dalhuisen: Janssen: Current Employment. Vandervennet: Janssen: Current Employment.

scholarly journals Tracking Daratumumab Clearance Using Mass Spectrometric Approaches: Implications on M Protein Monitoring and Reusing Daratumumab

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2707-2707
Author(s):  
Nadine Abdallah ◽  
David L Murray ◽  
Angela Dispenzieri ◽  
Prashant Kapoor ◽  
Morie A. Gertz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Plasma Cell ◽  
Research Funding ◽  
Univariate Analysis ◽  
M Protein ◽  
Urine Protein ◽  
Advisory Committees ◽  
Plasma Cell Disorders

Abstract Background: MASS-FIX is a screening method for serum and urine monoclonal proteins in multiple myeloma and related plasma cell disorders, which uses immunoglobulin enrichment coupled with matrix-assisted laser desorption ionization time-of-flight mass-spectrometry (MALDI-TOF). In addition to superior sensitivity over conventional gel-based techniques, MASS-FIX can distinguish therapeutic monoclonal antibodies (MoAb) from patient's M protein. As the utilization of therapeutic MoAbs increases, it is essential to understand the persistence pattern of these therapeutic antibodies in the serum. We designed this study to evaluate the duration of daratumumab detection by MASS-FIX in the serum of treated patients. Methods: We used a prospectively maintained database at Mayo clinic to identify patients with multiple myeloma and related plasma cell disorders who were treated with a daratumumab-containing regimen anytime during their disease course and had serial MASS-FIX data available after discontinuation of daratumumab. A univariate analysis was performed to assess for factors that may impact the clearance of daratumumab. Results: We included 125 patients with plasma cell disorders who received daratumumab as first or subsequent line of treatment between March 15 th, 2016, and March 4 th, 2020. The median age was 60.2 years and 57% were male. The most common diagnoses were multiple myeloma (70%) and light chain amyloidosis (18%). Daratumumab-based treatments were initiated after a median of 28.8 (IQR: 6.4-76.3) months from initial diagnosis. The most common regimen used was daratumumab, bortezomib and dexamethasone (23%); 26% underwent transplant after daratumumab-based induction. The median duration of treatment with a daratumumab-based regimen was 208 (IQR: 99-479) days. The median follow-up from the time of daratumumab discontinuation was 457 (95% CI: 346-NR) days. By last follow up, daratumumab was not detected by MASS-FIX in 93 (74%) patients but remained detectable in 32 (26%) patients. The median time from daratumumab discontinuation to disappearance of daratumumab by MASS-FIX was 160 (IQR: 107-233) days. On univariate analysis, the presence of ≥0.5 grams of urine protein was associated with earlier disappearance of daratumumab on MASS-FIX [risk ratio (RR): 2.0, P=0.02). The median time from daratumumab discontinuation to disappearance of daratumumab on MASS-FIX was 116 (95%CI: 76-160) days in patients with urine protein ≥0.5 grams and 203 (95%CI: 162-216) days in patients with urine protein &lt;0.5 grams (P=0.02). There was no association between the time to disappearance of daratumumab by MASS-FIX and old age ≥70 (RR: 0.9, P=0.81], male gender (RR: 0.9, P=0.60), eGFR &lt;60 (RR: 1.0, P=0.98), daratumumab schedule (every 1/2 weeks vs &gt;2weeks) (RR: 1.0, P=0.97), treatment duration (&lt;200 days vs ≥200 days) ( RR: 1.0, P=0.95), or transplantation status (RR: 1.0, P=0.98). Conclusion: The therapeutic monoclonal antibody daratumumab remains detectable in the serum of treated patients by MASS-FIX for several months after discontinuation and the duration varies between individual patients. This data has implications for diagnostic and monitoring testing and may provide guidance for reuse of daratumumab in clinical trials and practice. Proteinuria is associated with earlier disappearance of daratumumab by MASS-FIX and may have implications in patients with amyloidosis and monoclonal immunoglobulin deposition disease (MIDD). Further studies are needed to identify additional factors associated with the timing of disappearance. Disclosures Murray: Mayo Clinic: Other: Has received patents for the Mass-Fix technology which has been licensed to the Binding Site with potential royalties.. Dispenzieri: Takeda: Research Funding; Alnylam: Research Funding; Pfizer: Research Funding; Oncopeptides: Consultancy; Sorrento Therapeutics: Consultancy; Janssen: Consultancy, Research Funding. Kapoor: Karyopharm: Consultancy; Cellectar: Consultancy; BeiGene: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Amgen: Research Funding; Ichnos Sciences: Research Funding; Regeneron Pharmaceuticals: Research Funding; Glaxo SmithKline: Research Funding; Karyopharm: Research Funding; Sanofi: Research Funding; Takeda: Research Funding; AbbVie: Research Funding. Gertz: Akcea Therapeutics, Ambry Genetics, Amgen Inc, Celgene Corporation, Janssen Biotech Inc, Karyopharm Therapeutics, Pfizer Inc (to Institution), Sanofi Genzyme: Honoraria; Ionis Pharmaceuticals: Other: Advisory Board; Akcea Therapeutics, Alnylam Pharmaceuticals Inc, Prothena: Consultancy; Aurora Biopharma: Other: Stock option; AbbVie Inc, Celgene Corporation: Other: Data Safetly & Monitoring. Dingli: Alexion: Consultancy; Novartis: Research Funding; Apellis: Consultancy; Janssen: Consultancy; Sanofi: Consultancy; GSK: Consultancy. Kumar: Antengene: Consultancy, Honoraria; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bluebird Bio: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Merck: Research Funding; Roche-Genentech: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Beigene: Consultancy; Oncopeptides: Consultancy; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Carsgen: Research Funding; Tenebio: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding.

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