MELISSE, a Large Multicentric Observational Study to Determine Criteria and Risk Factors of Thromboembolism for Patients with Multiple Myeloma Treated with Immunomodulator Drugs

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 809-809
Author(s):  
Xavier Leleu ◽  
Laurent Daley ◽  
Philippe Rodon ◽  
Cyrille Hulin ◽  
Ahmad AL Jijakli ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Research Funding ◽  
Vascular Complications ◽  
Vte Prophylaxis ◽  
Line Therapy ◽  
Risk Patients ◽  
Data Missing ◽  
Third Line ◽  
Line Of Therapy

Abstract Abstract 809 Background. Immunomodulator drugs (IMiDs) are new and very promising oral agents for initial treatment and for treatment of relapse in Multiple Myeloma (MM); however, IMiDs are also associated with an increased risk of venous thromboembolism (VTE) which necessitates routine prophylaxis. Guidelines (Palumbo et al, Leukemia 2008) have proposed either aspirin or low weight molecular heparin (LWMH) for VTE prophylaxis based on a VTE risk stratification. Controversies remain regarding the best choice of VTE prophylaxis regimen in MM patients treated with IMiDs-based therapy and the criteria for the VTE risk definition. More studies are needed to better determine the criteria required for patients to receive either aspirin or LWMH as VTE prophylaxis. We designed a large multicentre observational study aimed at prospectively evaluating the incidence and risk factors of thromboembolism associated with IMiDs [either lenalidomide (Len) or thalidomide (Thal)] therapy in MM. Method. A total of 519 patients with MM treated with first to third line of therapy were included in this study. Patients were treated with IMiDs-based therapy at entry in the study, and those receiving VTE prophylaxis had to start this prior to start IMiDs (the choice was solely that of the clinician). Patients gave written informed consent according to the declaration of Helsinki. Various patient characteristics were recorded, such as age, sex, criteria of vascular complications, including adjuvant treatment such as EPO, bisphosphonates, radiotherapy, and previous history of either deep venous thrombosis (DVT) or pulmonary embolism (PE), or arterial vascular complications. The physicians were to record the risk of VTE occurrence, breakdown as low, mild and high, based on guidelines and their own appreciation of the risk. Occurrence of any thrombosis event (either venous or arterial) was to be recorded along with the descriptive characteristics of the event, how the event was managed and the outcome of the patient. The data were collected at entry in the study, and then at 4 and 12 months. Results. Out of the 519 patients, 35.66% had Thal-based and 64.34% had Len-based therapy. Overall, median age was 71, with 64.67% >65 years old and sex ratio was 249 male/268 female, similar in the 2 groups (data missing for n=2). One hundred and eighty patients were in first line therapy, 169 in second line therapy and 153 in third line therapy (data missing for n=17). Patients were treated with VTE prophylaxis as follow (data missing for n=8); 293 (57.34%) aspirin, 91 (17.81%) LWMH and 46 (9.00%) vitamin K antagonists. Surprisingly, 81 (15.85%) patients had no VTE prophylaxis. Aspirin was administered in 164 (69.79%) of low risk patients and LWMH in 33 (45.83%) of high risk patients. Investigators recorded 13 (3.65%) VTE at the 3564-months visits currently completed, with 7 DVT, 2 PE and 4 DVT+PE. Of these 13 VTE, 8 patients had aspirin, 1 had LWMH and 4 had no prophylaxis treatment. Of the 13 VTE, 1 patient was considered to have high risk of vascular complication and 12 patients either low or moderate risk, according to guidelines. The occurrence of VTE was unrelated to the regimen-based IMiD therapy and the line of therapy. Conclusion. This study further demonstrates that occurrence of VTE is low in IMiDs-based treated MM patients upon VTE prophylaxis, and that VTE prophylaxis is needed for patients treated with IMiDs-based therapy. However, despite VTE prophylaxis, we observed occurrence of VTE. These results question whether the current guidelines on VTE prophylaxis in MM patients treated with IMiDs-based therapy are accurate. Final results will be proposed with updated results at ASH 2010. Disclosures: Leleu: Celgene: Consultancy, Research Funding; Janssen Cilag: Consultancy, Research Funding; Leo Pharma: Consultancy; Amgen: Consultancy; Chugai: Research Funding; Roche: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Daley:LEO Pharma: Employment. Lamblin:LEO Pharma: Employment. Natta:LEO Pharma: Employment.

Final Analysis of MELISSE, a Large Multicentric Observational Study to Determine Risk Factors of Venous Thromboembolism in Patients with Multiple Myeloma Treated with Immunomodulator Drugs

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1235-1235 ◽  
Author(s):  
Xavier Leleu ◽  
Laurent Daley ◽  
Philippe Rodon ◽  
Cyrille Hulin ◽  
Charles Dauriac ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
High Risk ◽  
Incidence Rate ◽  
Research Funding ◽  
Final Analysis ◽  
Vte Prophylaxis ◽  
High Risk Patients ◽  
Increased Risk ◽  
Risk Patients

Abstract Abstract 1235 Background. Immunomodulator drugs (IMiDs) are associated with an increased risk of thromboembolic events (TE). Multiple Myeloma patients (MM) that can not benefit from novel agents, including IMiDs, only have 9 months survival. IMiDs must be stopped when TE occurs with the consequence of potential shortened life expectancy. MELISSE was designed to prospectively evaluate the incidence and risk factors of venous TE (VTE) associated with IMiDs in MM. We have presented the interim analysis of MELISSE at ASH 2010. A reduced incidence rate of early VTE was observed when a prophylaxis for VTE was started as compared to patients that had no prophylaxis. Interestingly, we also reported that most of the patients had received aspirin, while aspirin is not considered to exert any venous prophylactic effect. LMWH was primarily proposed to patients with high risk of TE according to physician's evaluation. We present the final analysis of MELISSE with updated results at 1 year. Method. A total of 524 MM treated with IMiDs-based therapy were included in 52 IFM centers. VTE prophylaxis was recommended prior to start IMiDs, the choice of which was left at the discretion of the investigator. Patients gave written informed consent according to the declaration of Helsinki. The physicians were to record the risk of VTE occurrence, categorized as low, moderate and high, based on guidelines and their own appreciation of the risk. Occurrence of any VTE was to be recorded along with the management of the event and the patient's outcome. The data were collected at entry in the study, and then after 4 and 12 months. Results. The median age was 70 years old, with 64.67% of patients >65 years old. Overall 36.0% had thalidomide-based and 64.0% had lenalidomide-based therapy, with 180 patients in first line and the remaining patients in 2nd and 3rd lines of therapy. The observed repartition of TE risk factors was as expected in a European population with myeloma. The risk of VTE was assessed as high in 14.2% patient and small or intermediate otherwise. Interestingly, approximately 70% of patients rated as low and intermediate risk received aspirin as a routine prophylaxis for VTE as compared to 20% in high risk patients. LMWH was primarily given to high risk patients, 45.8%. Surprisingly, 16.0% of patients had no VTE prophylaxis. Investigators recorded 29 (5.5% annual incidence rate) TE at 12 months, including 12 associated with PE. The incidence rate of TE was similar within the first 4 months (early occurrence, 3.5%) versus after 4 months (late, 2.5%). We have not identified any risk factor that would explain early versus late occurrence of VTE. Interestingly, the incidence of VTE was higher in patients that had no prophylaxis treatment, 8.5%, as compared to 4.4% and 5.9% in the LMWH and aspirin groups, respectively. There was no PE recorded in patients that were on LMWH prophylaxis. The VTE was equally breakdown across the 3 groups of risk factors. The bleeding adverse events were reported for 27 patients, mainly patients with aspirin. We isolated a model with 3 variables that independently predicted a higher risk to develop VTE in the multivariate model, and that comprised the male gender [OR 4.31 (95% CI 1.60 – 13.90)], the smoking habit [6.76 (1.73–22.42)] and the association to EPO [2.66 (1.04–6.58)]. Aspirin showed no significance, but with a p value at 0.55. The multivariate analysis is limited as certain subgroups with high risk factors might have received the optimal VTE prophylaxis, such as patients with bed rest and patients with prior history of VTE. These 2 groups rarely had aspirin. Survival data will be updated and presented at ASH 2011. Conclusion. This study further demonstrates that TE prophylaxis is required for MM treated with IMiDs-based therapy. There is a slight increase risk of VTE/PE with the use of aspirin as compared to LMWH, but a significant increase in bleeding events. Although we have identified risk factors of VTE in MM treated with IMiDs, for the first time, we could not identified VTE risk factors to guide investigators between LMWH and aspirin-based prophylaxis. The optimal dose and duration of LMWH remains to be determined. Disclosures: Leleu: LeoPharma: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen Cilag: Honoraria, Research Funding; Roche: Research Funding; Amgen: Honoraria; Novartis: Research Funding. Daley:LeoPharma: Employment. Hulin:Janssen: Honoraria; Celgene: Honoraria. Lamblin:LeoPharma: Employment. Natta:LeoPharma: Employment.

scholarly journals Incidence, Management and Outcomes of Arterial and Venous Thromboembolism after Chimeric Antigen Receptor Modified T Cells for B-Cell Lymphoma and Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-7
Author(s):  
Anna L. Parks ◽  
Swetha Kambhampati ◽  
Bita Fakhri ◽  
Charalambos Andreadis ◽  
Lissa Gray ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
T Cells ◽  
Venous Thromboembolism ◽  
B Cell ◽  
Research Funding ◽  
Vte Prophylaxis ◽  
Therapeutic Anticoagulation ◽  
Car T ◽  
History Of

Introduction: Chimeric antigen receptor modified T Cell (CAR-T) therapy is a rapidly developing treatment for patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) or multiple myeloma (MM). Although this population is at high risk for thrombosis, there are few data about rates of venous thromboembolism (VTE) and arterial thromboembolism (ATE) with CAR-T. Additionally, treatment with anticoagulation is complicated because of the prevalence of thrombocytopenia following CAR-T. Our goal was to determine the incidence, associated risk factors, management and outcomes of VTE and ATE in the 60 days following CAR-T therapy. Methods: We performed a single-center, retrospective cohort study of all patients who received inpatient CAR-T cells at UCSF Medical Center between January 2018 and May 2020 for R/R NHL or MM as standard-of-care or on a clinical trial. The outcomes of incident VTE and ATE were identified by ICD-10 codes and medical record review. Patient characteristics, pre-existing thrombosis risk factors, laboratory results, medications, and major or clinically relevant non-major bleeding or recurrent thrombotic complications were obtained through chart review. We used descriptive statistics to delineate risk factors, incidence, management and outcomes of thrombotic events. Results: Ninety-one patients who underwent CAR-T therapy were included in the analysis, 37 with NHL and 54 with MM. For NHL, mean age was 63 (range 38-82), and 41% were women. For MM, mean age was 62 (range 33-77), and 50% were women. Patients with NHL were treated with either investigational or Federal Drug Administration-approved CD19-directed therapies, and patients with MM were treated with a variety of investigational B-cell maturation antigen-directed (BCMA) therapies. For thrombotic risk factors, 13% of patients with NHL had a history of VTE, 3% had a history of ATE, 27% had a BMI ≥30, 59% had a recent procedure including central venous catheter (CVC) placement, 14% had an intensive care unit (ICU) stay, and 22% had an infectious complication in the 30 days pre- or post-CAR-T. Forty-one percent of patients with NHL had neurotoxicity of any grade, and 59% had CRS of any grade. At 30 days, 57% had a complete response, 41% had a partial response, 3% had stable disease. For MM, 6% of patients had a pre-existing history of VTE, 2% had a history of ATE, 19% had a BMI ≥30, 96% had a recent procedure, 11% had an ICU stay and 19% had an infection. Seventeen percent had neurotoxicity, and 85% had CRS. Thirty-two percent of patients with NHL and 48% with MM received pharmacologic VTE prophylaxis while undergoing CAR-T. For those who did not receive VTE prophylaxis, thrombocytopenia was the reason for holding prophylaxis, which occurred in 51% and 50% of NHL and MM patients, respectively. In the 60 days post-CAR-T, 4 (11%) patients with NHL were diagnosed with VTE-3 pulmonary embolism (PE) and 1 lower extremity deep vein thrombosis (DVT) associated with a previously placed inferior vena cava filter. Four (7%) patients with MM were diagnosed with VTE-1 PE and 3 upper extremity DVTs associated with CVCs. Five out of these 8 (63%) patients had symptomatic VTE, while the remainder were incidental on PETCT. Mean time from CAR-T infusion to VTE diagnosis was 20 days (range 6-39 days). There were no documented ATEs. Six out of 8 (75%) were treated with therapeutic anticoagulation. Of those who were anticoagulated, 4 patients received direct oral anticoagulants and 2 received low-molecular-weight-heparin. Duration was 3 months in 3 patients, 11 days in 1, 150 days in 1, and indefinitely in 1 with atrial fibrillation. Among all 8 patients with VTE, there were no bleeding events or recurrent thromboses regardless of whether or not they received anticoagulation. Discussion: In this cohort of patients with R/R NHL or MM who received either CD19- or BCMA-directed therapies, almost 1 in 10 developed VTE in the 60 days post-CAR-T. This occurred in the context of a high prevalence of risk factors for thrombosis and low rates of pharmacologic prophylaxis. Among those who developed VTE, the majority were treated with therapeutic anticoagulation for at least 3 months, without documented bleeding or recurrent VTE. Our findings provide crucial information on a common complication that can inform patients, clinicians and researchers and should be expanded upon in larger, prospective studies to identify optimal preventive and therapeutic strategies. Disclosures Fakhri: University of California San Francisco: Current Employment. Andreadis:Jazz Pharmaceuticals: Honoraria; Karyopharm: Honoraria; Incyte: Consultancy; Merck: Research Funding; Gilead/Kite: Consultancy; Novartis: Research Funding; BMS/Celgene/Juno: Honoraria, Research Funding; Genentech: Consultancy, Current equity holder in publicly-traded company. Wong:Janssen: Research Funding; Amgen: Consultancy; Roche: Research Funding; Fortis: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Research Funding; GSK: Research Funding. Shah:BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding; GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy.

scholarly journals Patient Profile and Treatment Patterns in a Commercially Insured Population with Follicular Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5880-5880
Author(s):  
Nathan H Fowler ◽  
Yanni Hao ◽  
Stephen Lim ◽  
Guifang Chen ◽  
Frank Li ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Second Line ◽  
First Line ◽  
Advisory Committees ◽  
First Line Therapy ◽  
Line Therapy ◽  
Third Line ◽  
Line Of Therapy

Introduction: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma in the Western hemisphere. Patient characteristics and burden of FL are incomplete and vary from previous studies. This study evaluated patient profile, including patient characteristics, treatment patterns, and duration using real-world data. Methods: Using the Truven MarketScan® databases, patients with FL who were newly initiated with FL indicated regimens were identified from 1/1/2010-12/31/2013 (initial treatment identification period). Patients were selected if they were ≥18 years old, had 1 FL ICD-9 code (202.0) as primary or secondary diagnosis, at least 1 FL commonly prescribed systemic anti-cancer therapy after the diagnosis, and did not use any FL indicated regimen in the past 6 months prior to first agent included in the initial treatment identification period. These patents were followed ≥3 months or to June 30, 2018. Primary outcomes were the distribution of regimens by line, the number of patients who switched from first- to second-line therapies, and from second- to third-line therapies. The treatment duration by line of therapy and regimen were also analyzed. Discontinuation was defined as 3 months without receiving a regimen after treatment. Results: This study identified 4,970 patients who initiated treatment for FL. Of these patients, 48.1% were female (n=2,390), with a mean age of 62.0 (SD: 14.0) years. The average follow-up time was approximately 2 years (median: 733 days). In this analysis, 4,970 patients with FL received first-line therapy for 153 days (median: 94 days), 1,985 received second-line therapy (39.9% of patients who received first-line therapy) for 208 days (median: 80 days), and 664 received third-line therapy (13.4% of patients who received first-line therapy) for 117 days (median: 43 days). Of the 4,970 patients on first-line therapy, 453 (9.1%) remained on first-line therapy, 2,532 (51.0%) discontinued treatment, and 1,985 (39.9%) patients switched to the next line of therapy during the follow-up period. Of the 1,985 patients who switched to second-line therapy, 328 (16.5%) remained by the end of follow-up period, 993 (50.0%) discontinued, and 664 (33.4%) switched to the next line of therapy during the follow-up period. Of the 664 patients who switched to third-line therapy, 125 (18.8%) remained, 269 (40.5%) discontinued, and 270 (40.7%) switched to the next line of therapy. The most common first-line regimens in descending order received by patients were rituximab (n=1,478, 29.7%), R-CHOP (n=1,368, 27.5%), BR (n=1,050, 21.1%), R-CVP (n=371, 7.5%), and FCR (n=63, 1.3%). Second-line treatment regimens were (N=1,985) rituximab (n=992, 50.0%), BR (n=202, 10.2%), R-CHOP (n=138, 7.0%), and R-CVP (n=120, 6.1%). Third-line treatment regimens were (N=664) rituximab (n=228, 34.3%), BR (n=91, 13.7%), R-CHOP (n=75, 11.3%), cyclophosphamide (n=35, 5.3%) and R-CVP (n=31, 4.7%). Conclusion: This data set describes the percentage of patients that transition from first- to second-line and second- to third-line treatment for FL. The primary regimens used across the treatment lines conform to those recommended by the NCCN guidelines. In addition, smaller numbers of non-recommended regimens were reported. Disclosures Fowler: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; ABBVIE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hao:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Lim:Novartis Pharmaceuticals Corporation: Employment. Chen:Novartis Pharmaceuticals Corporation: Consultancy, Employment. Li:Novartis Pharmaceuticals Corporation: Employment. Arcona:Novartis Pharmaceuticals Corporation: Employment.

scholarly journals VTE Incidence in RRMM Patients Treated with NOVEL Agents: A Monocentric Real Life Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4972-4972
Author(s):  
Gaetano Giuffrida ◽  
Concetta Conticello ◽  
Valeria Calafiore ◽  
Enrica Antonia Martino ◽  
Silvia Giamporcaro ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Research Funding ◽  
Real Life ◽  
Low Risk ◽  
Novel Agents ◽  
Vte Prophylaxis ◽  
High Risk Patients ◽  
Risk Patients ◽  
Low Incidence

INTRODUCTION: Venous thromboembolism (VTE) is very common in patients with malignancies. Compared to the general population, patients with multiple myeloma (MM) have a 9-fold increased risk of developing VTE. In patients treated with thalidomide or lenalidomide, current guidelines recommend systematic VTE prophylaxis with ASA in low risk patients while vitamin K antagonists (VKA) or low weight molecular heparin (LWMH) or unfractionated heparin (UFH) in high-risk patients, based on the type of anti-MM treatment that patients receive and patient-related individual risk factors (e. g. history of VTE). However, little is known on VTE prophylaxis in patients treated with next generation anti-myeloma drugs, such as pomalidomide, carfilzomib and monoclonal antibodies daratumumab and elotuzumab. Here, we describe the incidence of VTE in MM patients treated with third generation novel agents in real life. In addition, we stratify patients on drugs category-based regimens to evaluate strategy of VTE prophylaxis between different groups of patients. MATERIALS AND METHODS: A retrospective cohort of 137 patients affected by relapsed and/ or refractory multiple myeloma treated with novel agents was analyzed. Patients were followed at the Division of Hematology of Catania from April 2013 to June2019. Our series includes 75 patients exposed to Pomalidomide and Dexametasone (PomaD), 46 patients receiving Carfilzomib, Lenalidomide and desamethasone regimen (KRd), 14 patients exposed to Daratumumab(Dara), 27 patients to Daratumumab, Bortezomib and desamethasone (DaraVD), 4 patients to Daratumumab lenalidomide and desamethasone (DaraRd), and12 patients exposed to Elotuzumab and Lenalidomide (EloRd). Several patients were exposed to multiple lines of treatment with novel agents: the total number of analyzed treatments are 178. Patients were stratified to high or low risk for VTE: risk factors taken into account were obesity, history of VTE, central venous catheter, inhered thrombophilia, surgical procedures and comorbidities such as infections, immobilization, cardiac disease, chronic renal disease. Low risk patients had no or one risk factor; in case of two or more risk factors, the patients were classified as high risk. Low-dose aspirin (ASA 100 mg per os once daily) or equivalent was prescribed in low risk patients, low-molecular-weight heparin (LMWH) or equivalent was given to high risk patients. Only Dara treatment did not include standard prophylaxis in patients without risk factors. RESULTS: Real life observation revealed a low incidence of VTE (6 VTE-4,3%) in patients exposed to novel agents together with a standard prophylaxis in case of risk of thromboembolic complications. Forty patients were at high risk of VTE, while 97 patients were classified as low risk; VTE/PE occurred in 2 high risk patients who refused to make correct LMWH prophylaxis due to the discomfort of the subcutaneous administration, developing distal DVT respectively after cycle 1 and 2 of KRd. Two low risk patients treated with PomaD developed DVT of lower extremities during cycle 2 and 4; 2 low risk patients had pulmonary embolism during PomaD cycle 8. CONCLUSIONS: Low incidence of VTE in patients with RRMM receiving PomaD, KRd, EloRd, DaraVD, DaraRd, Dara or EloRd treatment is probably due to a correct risk assessment and subsequent prophylaxis in case of therapies including immunomodulators or in case of patients with high risk for thromboembolic complications. These data support the use of VTE risk stratification-based prophylactic strategies in myeloma patients treated with new drugs. Disclosures Conticello: Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. Di Raimondo:Takeda: Consultancy; Amgen: Consultancy, Honoraria, Research Funding.

In Multiple Myeloma Progression Free and Overall Survival in the Relapsed Setting Remains Poor with Early Exposure to Novel Agents: Experience from a Real-World Cohort

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4261-4261 ◽  
Author(s):  
Christopher P. Venner ◽  
Nizar J Bahlis ◽  
Paola Neri ◽  
Irwindeep Sandhu ◽  
Peter Duggan ◽  
...  
Keyword(s):  
Research Funding ◽  
Response Rate ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Third Line Therapy ◽  
First Relapse ◽  
Third Line ◽  
Line Of Therapy

Abstract Introduction: With the widespread adoption of novel agents (NA) in all lines of therapy patients are being exposed to both proteosome inhibitors (PIs) and immunomodulatory drugs (IMiDs) early in their treatment course. This has lead to marked improvements in survival in the frontline setting. Data is limited with respect to patient outcomes after exposure to both these drug classes in the real world setting. Here we present our experience examining outcomes after each line of therapy whereby bortezomib-based induction followed by lenalidomide-based therapy at first relapse has become the standard of care. We further explored the outcomes of patients who were exposed to both active classes of drugs within their first 2 lines of therapy. Patients and methods: This series includes patients seen through the provincial Alberta Myeloma and Dysproteinemia Program in Canada. Only patients treated between 2005-2013 were included to allow at least 2 years of follow-up beyond first line therapy. Only those treated with a NA-containing regimen as part of their first line treatment were examined. The cohort was split based on eligibility for autologous stem cell transplant (ASCT). Double exposed patients were those who had been treated with, but were not necessarily refractory to both an IMiD and PI within the first 2 lines of treatment. Outcomes were measured after first, second and third line therapy. Survival outcomes were measured in months (m). OS was measured from the start of each line of therapy until death or last follow-up. PFS was from the start of each line of therapy to relapse, death or last follow-up. Response was measured as per the most recent International Myeloma Working Group criteria. Near complete response (nCR) was used when the monoclonal protein disappeared on protein electrophoresis but was not confirmed by immunofixation. Results: Two hundred forty eight patients had received upfront therapy (non-ASCT = 113 and ASCT = 135). One hundred twenty seven had received second line therapy (non-ASCT = 62 and ASCT = 65). Sixty-four had received third line therapy (non-ASCT = 31 and ASCT = 33). The median OS and PFS after each line of therapy are shown in table 1. After first line therapy the OS (p < 0.001) and PFS (p< 0.001) were significantly better in the ASCT cohort. There were no significant differences in survival outcomes based on transplant eligibility in subsequent lines of therapy (figure 1A and B). The overall response rate to third line therapy was 45% (VGPR = 14% and nCR = 7%) for non-ASCT patients and 52% (VGPR = 15% and nCR = 6%) for ASCT patients. Fifty-five percent of non-ASCT patients failed to respond during third line therapy (34% with progressive (PD) and 21% with stable disease (SD)). Forty-eight percent of ASCT patients failed to respond (PD = 27% and SD = 21%). Forty-seven patients were double exposed within the first 2 lines of therapy (non-ASCT = 26 and ASCT = 21). In this cohort, the OS and PFS after double exposure (i.e. third line therapy) was 15m and 5m respectively with no significant difference based transplant eligibility (figure 1C and D). The response rate to third line therapy was 46% (VGPR = 17% and nCR = 8%) for ASCT patients and 43% (VGPR = 14% and nCR = 5%) for non-ASCT patients. Fifty-five percent failed to respond (PD = 38% and SD = 17%) in the non-ASCT group. Fifty-seven percent failed to respond (PD = 38% and SD = 19%) in the ASCT group. Summary: The introduction of NAs earlier in the management of patients with myeloma has improved OS. This is driven by improvements in PFS to frontline therapy and after first relapse. However, with current therapeutic approaches patients will be exposed to both IMiDs and PIs much earlier in their disease. In many jurisdictions, the limited treatment options in third line and beyond, especially in double exposed patients, poses a significant therapeutic challenge. Durable responses are limited in this setting with most patients relapsing after only 6 months. In addition, approximately a third of patients have overtly progressive disease. Interestingly, front-line ASCT eligibility had no impact on outcome with subsequent relapses, emphasizing the fact that ASCT only improves the outcome for the line in which it is employed. Further study regarding resistant mechanism and clonal evolution after exposure to both IMiDs and PIs will be important in developing rationally designed therapeutic regimens for this population. Disclosures Venner: J&J: Honoraria, Research Funding; Amgen: Honoraria; Celgene: Honoraria, Research Funding. Off Label Use: Some patients in this series will have received frontline lenalidomide which is not yet an approved indication for this drug in Canada.. Bahlis:Johnson & Johnson: Speakers Bureau; Johnson & Johnson: Consultancy; Amgen: Consultancy; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Johnson & Johnson: Research Funding. Neri:Celgene: Research Funding. Sandhu:Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Duggan:Jansen: Honoraria; Celgene: Honoraria. Belch:Janssen-Cilag: Consultancy. Jimenez-Zepeda:Celgene: Honoraria; J&J: Honoraria; Amgen: Honoraria.

scholarly journals Analyzing Risk of Infection with Anti-CD38 Monoclonal Antibody Therapy for Patients with Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 49-49
Author(s):  
Augustine Hong ◽  
Augusta Eduafo ◽  
Hannah Schmikla ◽  
George Brown ◽  
Gayathri Ravi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Research Funding ◽  
Advisory Board ◽  
Risk Of Infection ◽  
Factors Associated ◽  
History Of ◽  
Grade 3 ◽  
Line Of Therapy ◽  
Significant Factors

Monoclonal antibodies targeting CD38 are emerging as a mainstay of therapy for Multiple Myeloma (MM) in the relapse setting as well as upfront. These antibodies not only target CD38 on myeloma cells inducing anti-tumor pleiotropic effects, they also influence normal CD38-expressing cells, including normal plasma cells, natural killer cells and immunosuppressive regulatory cells (van de Donk et al , 2018). These cells play a key role in innate as well as humoral immunity and provide protection against a variety of infectious insults; hence, their depletion in MM patients (pts) can be expected to have deleterious immunological effects due to the dismantling of an effective immune responses in a population already strained by dysfunctional immunity. While it has been previously shown that NK cells decline with exposure to daratumumab (DARA) (Casneuf et al , 2017), its clinical impact on the incidence of infection has yet to be elucidated because clinical trials have shown conflicting results, while POLLUX and CASTOR trials showed generally similar rates of grade 3 or 4 infections (28·3% vs. 22·8% and 21·4% vs. 19·0%, respectively, the ALCYONE trial, reported that grade 3-4 infections were higher in the DARA arm (23·1% vs. 14·7%). Here, we aim to explore the impact of different risk factors on infection during DARA therapy. Methods: We retrospectively reviewed patient records who received DARA-containing regimens for MM between Jan 2016 and Jan 2020. The history of infection, prior therapies, rate of infection during therapy with DARA, hospitalizations, baseline and nadir absolute counts of lymphocyte, monocyte and neutrophil population were extracted. Pts who had less than 1 month of DARA were excluded. Survival was measured from time of DARA start. Survival distribution was estimated using Kaplan-Meier methods and differences of OS, PFS between groups was examined by Wilcoxon test. The effect of treatment on OS and PFS was estimated using a Cox model after controlling for the effects of different variables. Results: Of 123 pts reviewed, median line of therapy was 3 (range: 0-9). Median time from diagnosis was 52 months (range: 0- 232 months). 43 pts (35%) were Black and 77 (63%) Caucasian. Median age was 70 (range 34-94 y/o). 86 (70%) were IgG, 24 were IgA (20%) and 10 light chain myeloma (10%). 24 (20%) had stage I, 37 (30%) had stage II and 61 (50%) had ISS stage III. 66 (53%) pts had transplant as prior therapy and the rest did not undergo transplant. 29 (24%) pts had DARA as a single agent, 66 (53%) in combination with IMiDs and 28 (23%) pts in combination with PI. Median duration of therapy was 133 days (range 30-1245 days). Median ANC 1243 /ml (range: 420-1120). Median ALC 710 /mL (170-8020). Median AMC was 455 /mL (0-2300). 31 pts had history of prior infections and the rest did not. 39 pts had infection during DARA. Overall, there were 125 hospital admission encounters for whole cohort occurred in 36% of cases, more than half of them (55%) were attributable to an infectious process. Bacterial pathogens accounted for the majority of infection. Pts with infection during DARA therapy had statistically significant nadir ALC (median 560 /ml) compared to pts without any infection. The univariate analysis showed age, history of infection, nadir ALC less than 600/ml and number of prior line of therapy as significant factors associated with infection rate during DARA therapy. Multivariate analysis after controlling for these factors shows only Low nadir ALC less than 600 /ml, hazard ratio (HR): 2.15, 95% confidence interval (CI): 1.19-3.76, and history of infection, HR: 1.87, 95% CI: 1.11-2.92, stands out as statistically significant factor. The whole cohort were divided based on ALC&lt;600 during the therapy or history of previous infection; the group with none of these two risk factors was assigned as low risk, the group with either of those as intermediate risk and the pts with both risk factor were characterized as high-risk group (Figure-1). Conclusion: Here we showed that infections is frequent among MM pts treated with DARA-containing regimen and assessed risk factors associated infection during DARA therapy. Dropping ALC and history of prior infection are significant factors associated with higher risk of infection during DARA therapy. These finding suggests vigilance for, and identification of risk factor are warranted for treating MM patient with DARA. The risk model is warranted to be examined in a prospective study. Disclosures de Lima: Pfizer: Other: Personal fees, advisory board, Research Funding; BMS: Other: Personal Fees, advisory board; Incyte: Other: Personal Fees, advisory board; Kadmon: Other: Personal Fees, Advisory board; Celgene: Research Funding. Malek:Cumberland: Research Funding; Takeda: Other: Advisory board , Speakers Bureau; Bluespark: Research Funding; Sanofi: Other: Advisory board; Clegene: Other: Advisory board , Speakers Bureau; Amgen: Honoraria; Medpacto: Research Funding; Janssen: Other: Advisory board, Speakers Bureau.

scholarly journals Risk Factors Associated with Development of Extramedullary Disease in Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5596-5596
Author(s):  
Martin Stork ◽  
Sabina Sevcikova ◽  
Marta Krejci ◽  
Zdenek Adam ◽  
Viera Sandecka ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Board Of Directors ◽  
Research Funding ◽  
Poor Prognosis ◽  
First Line ◽  
Advisory Committees ◽  
Line Of Therapy

Abstract Background Multiple myeloma (MM) is the second most common hematological malignancy characterized by plasma cell (PC) infiltration of the bone marrow. Unfortunately, better imaging techniques convey multiple reports about increased incidence of the so-called extramedullary disease of MM (EM), an aggressive, mostly resistant entity with poor prognosis for patients. EM probably develops because of 'bone marrow escape' of PC subclone that migrates out of the BM infiltrating soft tissues losing dependence on the BM microenvironment, either partially or completely. There are two types of EM - primary, found at the time of MM diagnosis, and secondary, found at the time of MM relapse. However, there are very few reports about EM. Aims This study aims to analyze risk factors connected to EM development. Methods Data from the Registry of Monoclonal Gammopathies (RMG) were analyzed. The RMG represents a database for collection of clinical data concerning diagnosis, treatment and follow-up of Czech MM and other monoclonal gammopathies patients. In total, data of 4985 MM patients were collected into the RMG database between 2007 and June 2017. Our analysis compared patients who developed EM at initiation of first or higher line of therapy with patients without EM during at least 5-year-long follow-up (patients who died earlier included). Logistic regression analysis was used to assess the association of baseline characteristics at MM diagnosis with EM occurrence at first line and relapse, respectively. Results In total, 4985 MM patients data were collected into the RMG database between 2007 and 2017. Patients were treated with bortezomib, lenalidomide, thalidomide, pomalidomide, ixazomib and daratumumab. Regardless of treatment, EM patients responded worse than MM patients did to any form of treatment. While primary EM patients had similar PFS as MM patients, OS was significantly worse (48.7 vs 60.6 months, resp.). Secondary EM patients did even worse, with PFS 8.7 months and OS 23.8 months only. We found 543 MM patients (10.9%) who developed EM during the entire follow-up. Out of these EM patients, we found 309 patients who were diagnosed with primary EM at initiation of first line of therapy. At initiation of 2nd line of treatment, we found 111 secondary EM patients. At 3rd, 4th and 5th, we found 61, 39 and 23 EM patients, resp. Finally, 309 patients who developed EM at initiation of 1st line and 234 patients who developed EM at initiation of further treatments were compared to 2092 patients who did not develop EM during the entire course of the disease. Overall, occurrence of EM at 1st or higher lines of treatment was associated with younger age, male sex, low ISS, D-S substage A, low B2 microglobulin, low creatinine, high hemoglobin, elevated thrombocytes, other types of M-Ig than IgG and presence of bone lesions. For EM cases found only at initiation of 1st line (primary EM), we found association with high ECOG status, low LDH, low M-protein quantity and low % of plasma cells infiltration in the bone marrow. For EM cases found at MM relapse (secondary EM), we found association with high D-S stage, high LDH, high CRP, high Ca, del13q and gain1q. Conclusion EM remains an aggressive disease with poor prognosis regardless of use of novel drugs. Surprisingly, in our group of patients, most EM disease developed early in the course of the disease - more than 60% at first relapse. We analyzed risk factors connected to development of EM and found that LDH, hemoglobin, thrombocytes and M-Ig status were associated with EM development. We suggest that in such patients, PET/CT or whole body MRI should be performed regularly to ensure early detection of EM. Grant support: AZV 17-29343A. Disclosures Maisnar: BMS: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; 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; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Hajek:Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding.

scholarly journals Real-Life Experience with Pomalidomide plus Low-Dose Dexamethasone in Patients with Relapsed and Refractory Multiple Myeloma: A Retrospective and Prospective Study

Medicina ◽  
2021 ◽  
Vol 57 (9) ◽  
pp. 900
Author(s):  
Maria Livia Del Giudice ◽  
Alessandro Gozzetti ◽  
Elisabetta Antonioli ◽  
Enrico Orciuolo ◽  
Francesco Ghio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Low Dose ◽  
Life Experience ◽  
Real Life ◽  
The Third ◽  
Line Therapy ◽  
Third Line ◽  
Line Of Therapy ◽  
Real Clinical Practice

Background and Objectives: The treatment of Myeloma after the second relapse is still challenging. The aim of the study was to investigate the outcomes of the POM-DEX regimen in real clinical practice. Materials and Methods: We retrospectively and prospectively analyzed 121 patients with MM treated with POM-DEX in three Italian sites in Tuscany. We assessed the efficacy based on IMWG Uniform Response Criteria in 106 patients who had received at least two courses of the POM-DEX regimen. The median time from diagnosis to use of POM-DEX was 65 months. POM-DEX median use was in the fourth-line therapy. 63.6% were exposed to lenalidomide or thalidomide, 40.5% to bortezomib or carfilzomib or ixazomib, 5.8% to mAbs in the immediately preceding line of therapy. Results: ORR was 43.4%. Median PFS and OS were 8.5 and 14 months. Eighty-nine patients received more than two courses: their median PFS and OS were 11 and 16 months. When used as the third line of therapy, median PFS and OS were 9 and 20 months and, when patients received POM-DEX for more than two courses, median PFS and OS were 14.5 and 22.5 months. Conclusions: POM-DEX is effective in RRMM, regardless of the latest exposure to IMiDs, PIs, and mAbs in the previous line of therapy.

scholarly journals Improving Rates of Venous Thromboembolism Prophylaxis in Multiple Myeloma Patients on Immunomodulatory Drugs

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2235-2235
Author(s):  
Houry Leblebjian ◽  
Joanna Hamilton ◽  
Sydney Smith ◽  
Jacob Laubach ◽  
Nancy Berliner ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Assessment ◽  
Multiple Myeloma ◽  
Venous Thromboembolism ◽  
High Risk ◽  
Low Risk ◽  
Immunomodulatory Drugs ◽  
Vte Prophylaxis ◽  
Nccn Guidelines ◽  
Risk Patients

Abstract BACKGROUND: Multiple myeloma patients who receive immunomodulatory drugs (IMiDs: lenalidomide, thalidomide, and pomalidomide) have an increased risk of developing venous thromboembolism (VTE). Guidelines for thromboprophylaxis are based on additional patient and disease characteristics. We describe our single-institution experience with VTE prophylaxis and an intervention to improve VTE risk assessment and prophylaxis. METHODS: A retrospective review using an internal patient database assessed VTE in multiple myeloma patients being treated with IMiDs from 2000-2016. VTE risk factors for each patient were assessed to determine alignment with thromboprophylaxis guidelines. A Quality Improvement (QI) phase from April 1, 2017 to December 31, 2017 added pharmacy oversight to perform an independent VTE risk assessment. Every patient started on an IMiD during this period underwent a separate VTE risk assessment by a pharmacist or hematologist. Each patient was categorized as high or low VTE risk based on NCCN guidelines. The results and recommendations for VTE prophylaxis were given to the myeloma provider. Results: In the initial retrospective review, 107 patients were identified who developed VTE during treatment of multiple myeloma with an IMiD despite thromboprophylaxis in 91 patients (85% of total; 78% on aspirin). The most common VTE risk factors per NCCN guidelines included cardiac disease (n=70), obesity (n=32), chronic kidney disease (n=27), and prior history of VTE (n=18). Eight patients received anticoagulant-based thromboprophylaxis. In the QI phase, 39 multiple myeloma patients were started on IMiDs. The risk assessment classified 17 as low-risk and 22 as high-risk. Of the high-risk patients, 14 (64%) were placed on an anticoagulant for thromboprophylaxis. Eleven (79%) of the anticoagulants used were direct oral anticoagulants (DOACs), 2 (14%) were a low-molecular weight heparin, one (7%) warfarin. The number of thromboembolic events that occurred were 6 (15%): 4 were high-risk on aspirin and 2 were low-risk on aspirin. The 2 low-risk patients who developed VTE had additional provoking factors (active infection, central line placement, smoking, a long driving trip). Eight high-risk patients were given aspirin. Out of the 8, 3 patients developed VTE and were then switched to anticoagulation. One high-risk patient received aspirin because of moderate thrombocytopenia and subsequently developed a VTE. No patients on anticoagulation developed a VTE. The number of complications attributed to thromboprophylaxis were 2 (5%). Two minor bleeding events occurred in patients who were on DOACs (1 epistaxis and 1 grade 1 GI bleed). Both patients continued DOAC anticoagulation after the event resolved. Conclusions: This two-phase QI study showed that multiple myeloma patients at high risk for VTE benefit from guideline-based thromboprophylaxis facilitated through a pharmacy-based system. DOAC's ease of use offer patients and providers an agreeable option that may improve compliance of VTE guidelines. However, prospective studies with DOACs in multiple myeloma are urgently needed to support this. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals Real-World Treatment Patterns in Relapsed or Refractory Multiple Myeloma: Evidence from a Cohort Review in the United Kingdom

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5947-5947
Author(s):  
Huamao Mark Lin ◽  
Keith L Davis ◽  
James A. Kaye ◽  
Katarina Luptakova ◽  
Saurabh Nagar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Progression ◽  
Research Funding ◽  
Complete Response ◽  
Additional Benefit ◽  
Line Treatment ◽  
Second Line ◽  
Line Therapy ◽  
First Relapse ◽  
Third Line

Abstract INTRODUCTION: Despite advancements in induction and maintenance therapies leading to improved response rates and overall survival (OS), virtually all patients with multiple myeloma (MM) eventually relapse. Improvement in outcomes in relapsed and/or refractory multiple myeloma (RRMM) remains an area of unmet need, yet there is a shortage of data describing typical treatment patterns in these patients in real-world practice settings. Such data may help inform future health technology assessments and other regulatory evaluations of current and new therapies in RRMM. To help address this information gap, we analyzed retrospective data from a cohort of RRMM patients in the United Kingdom (UK). METHODS: A retrospective medical record review was conducted in a cohort (n = 216) of patients with RRMM in the UK. Patients were selected (based on randomly generated first letter of last name) from the caseloads of 41 hematology/oncology providers across the UK. Specific inclusion criteria were: ≥18 years of age at initial MM diagnosis; first determined to have RRMM between January 1, 2009 and December 31, 2011, where RRMM was defined by (1) receipt of a first-line (induction) treatment regimen of chemotherapy with or without stem cell transplant (SCT) and with or without post-induction/SCT maintenance therapy and (2) disease progression while on or at any time after completion of first-line therapy. Patients were retrospectively assessed on second- and third-line treatment regimens received, treatment duration, and reasons for treatment discontinuation from date of first relapse or progression (study index date). All analyses were descriptive and exploratory in nature. RESULTS: Demographic and clinical characteristics of the study sample are presented in Table 1. Mean (SD) age at study index (first relapse, or RRMM diagnosis) was 65.6 (8.7) years, with approximately half of patients (53%) having advanced age (≥65 years). The study sample was 62.5% male and more than two-thirds of patients (69%) were still alive at the time of the medical record review. Among the 216 patients studied, 208 (97%) received ≥1 additional line of systemic chemotherapy after first relapse (Table 2); 94 patients (43%) received ≥2 additional lines of therapy (i.e., at least second- and third-line therapy) during the observation period. The most common second-line regimen was bortezomib + dexamethasone with or without other agents (66% of second-line initiators), followed by lenalidomide + dexamethasone with or without other agents (20%). Median duration of second-line treatment was 6 cycles over a median of 5.4 months. Among the 98% of patients who discontinued second-line treatment, a majority (62%) stopped therapy due to reaching complete response with no additional benefit expected; 33 patients (16%) discontinued second-line treatment due to disease progression and 8% discontinued due to toxicities. Lenalidomide + dexamethasone with or without other agents was the predominant third-line regimen (67% of third-line initiators); bortezomib + dexamethasone with or without other agents was the next most common third-line regimen (14%). Among the 94 patients receiving third-line treatment, median duration was 6 cycles over a median of 5.7 months. The leading reason for third-line discontinuation was disease progression (48%); 30% of patients discontinued because they reached complete response with no anticipated additional benefit, and 20% discontinued because of loss or lack of response to therapy. CONCLUSIONS: In the RRMM cohort reviewed here, bortezomib-containing regimens were the predominant second-line therapy and lenalidomide + dexamethasone was the most common third-line regimen. The most common reasons for discontinuation of RRMM treatments were disease progression and physician-judged achievement of complete response with no additional benefit expected. While the most common reason for therapy discontinuation in second-line treatment was reaching complete response with no additional benefit expected, in third-line therapy it was disease progression. With growing evidence in the RRMM literature that treatment to progression may be superior to a fixed duration of therapy, as well as evidence of premature discontinuation being associated with inferior outcomes, the relatively short second-line duration reported here (<6 months) further highlights a potential unmet need in this disease area. Disclosures Lin: Takeda: Employment. Davis:Takeda: Research Funding. Kaye:Takeda: Research Funding. Luptakova:Takeda Oncology: Employment. Nagar:Takeda: Research Funding. Seal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership.

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