TY - JOUR
T1 - Venous thromboembolism risk with contemporary lenalidomide-based regimens despite thromboprophylaxis in multiple myeloma
T2 - A systematic review and meta-analysis
AU - Chakraborty, Rajshekhar
AU - Bin Riaz, Irbaz
AU - Malik, Saad Ullah
AU - Marneni, Naimisha
AU - Mejia Garcia, Alex
AU - Anwer, Faiz
AU - Khorana, Alok A.
AU - Rajkumar, S. Vincent
AU - Kumar, Shaji
AU - Murad, M. Hassan
AU - Wang, Zhen
AU - Khan, Safi U.
AU - Majhail, Navneet S.
N1 - Funding Information:
Faiz Anwer reports personal fees and reimbursement for travel and accommodation from InCyte and Seattle Genetics outside the submitted work. Alok A. Khorana reports institutional research funding from Array BioPharma, Bristol‐Myers Squibb, Leap Oncology, and Merck; personal fees from AngioDynamics, Bayer, Halozyme, Janssen, Pfizer, Pharmacyclics, Pharmacyte Biotech, and Seattle Genetics; and reimbursement for travel and expenses from Bayer, Janssen, and Pfizer, all outside the submitted work. S. Vincent Rajkumar reports author royalties from UpToDate outside the submitted work. Shaji Kumar reports institutional research funding from AbbVie, Celgene, Janssen Oncology, Kite Pharma, MedImmune/AstraZeneca, Merck, Novartis, Roche/Genentech, Sanofi, and Takeda; personal fees from AbbVie, Adaptive Biotechnologies, Amgen, Celgene, Genecentrix, Genentech/Roche, IRC, Janssen Oncology, Kite Pharma, MedImmune/AstraZeneca, Merck, Oncopeptides, Reddys Laboratories, and Takeda, all outside the submitted work. Navneet S. Majhail reports personal fees from Anthem Inc, Atara Biotherapeutics, Incyte, and Mallinckrodt, plc; and reimbursement for travel and expenses from Atara Biotherapeutics and Incyte, all outside the submitted work. The remaining authors made no disclosures.
Publisher Copyright:
© 2020 American Cancer Society
PY - 2020/4/15
Y1 - 2020/4/15
N2 - Background: Thromboprophylaxis is routinely used with lenalidomide-based regimens in multiple myeloma because of a substantial risk of venous thromboembolism (VTE). However, little is known about the incidence of VTE with contemporary lenalidomide-based regimens. The objective of the current study was to estimate the incidence of VTE despite thromboprophylaxis with currently used lenalidomide-based regimens in patients with myeloma. Methods: The Ovid MEDLINE, Embase, and Cochrane databases were queried from study inception to January 2019 for keywords to cover the following concepts: “lenalidomide,” “venous thromboembolism,” and “multiple myeloma.” Phase 1, 2, and 3 clinical trials evaluating lenalidomide-based regimens with thromboprophylaxis were included. The pooled incidence rate of VTE was estimated using a random-effects model. Results: The search generated 1372 citations, with 51 clinical trials and 9069 patients included for analysis. The most common thromboprophylaxis agents were aspirin, low-molecular-weight heparin or warfarin, administered either per risk-stratification or at investigators' discretion. The pooled incidence of VTE in trials of patients who had newly diagnosed and relapsed/refractory myeloma was 6.2% (95% CI, 5.4%-7.1%) over median treatment durations ranging from 2 to 34 cycles, which translated into 1.2 VTE events per 100 patient-cycles (95% CI, 0.9-1.7 VTE events per 100 patient-cycles). Among contemporary regimens, the risk of VTE was low with combined lenalidomide and low-dose dexamethasone (0.2 [95% CI, 0.1-0.6] events/100 patient-cycles) and lenalidomide maintenance (0.0 [95% CI, 0.0-0.7] events per 100 patient-cycles). VTE risk was higher with combined lenalidomide and low-dose dexamethasone plus proteasome inhibitors (1.3 [95% CI, 0.7-2.3] events per 100 patient-cycles). Conclusions: Despite adequate thromboprophylaxis, lenalidomide-based regimens have a substantial risk of VTE in controlled clinical trial settings. Further studies are needed on new thromboprophylaxis strategies with regimens that have a high VTE risk.
AB - Background: Thromboprophylaxis is routinely used with lenalidomide-based regimens in multiple myeloma because of a substantial risk of venous thromboembolism (VTE). However, little is known about the incidence of VTE with contemporary lenalidomide-based regimens. The objective of the current study was to estimate the incidence of VTE despite thromboprophylaxis with currently used lenalidomide-based regimens in patients with myeloma. Methods: The Ovid MEDLINE, Embase, and Cochrane databases were queried from study inception to January 2019 for keywords to cover the following concepts: “lenalidomide,” “venous thromboembolism,” and “multiple myeloma.” Phase 1, 2, and 3 clinical trials evaluating lenalidomide-based regimens with thromboprophylaxis were included. The pooled incidence rate of VTE was estimated using a random-effects model. Results: The search generated 1372 citations, with 51 clinical trials and 9069 patients included for analysis. The most common thromboprophylaxis agents were aspirin, low-molecular-weight heparin or warfarin, administered either per risk-stratification or at investigators' discretion. The pooled incidence of VTE in trials of patients who had newly diagnosed and relapsed/refractory myeloma was 6.2% (95% CI, 5.4%-7.1%) over median treatment durations ranging from 2 to 34 cycles, which translated into 1.2 VTE events per 100 patient-cycles (95% CI, 0.9-1.7 VTE events per 100 patient-cycles). Among contemporary regimens, the risk of VTE was low with combined lenalidomide and low-dose dexamethasone (0.2 [95% CI, 0.1-0.6] events/100 patient-cycles) and lenalidomide maintenance (0.0 [95% CI, 0.0-0.7] events per 100 patient-cycles). VTE risk was higher with combined lenalidomide and low-dose dexamethasone plus proteasome inhibitors (1.3 [95% CI, 0.7-2.3] events per 100 patient-cycles). Conclusions: Despite adequate thromboprophylaxis, lenalidomide-based regimens have a substantial risk of VTE in controlled clinical trial settings. Further studies are needed on new thromboprophylaxis strategies with regimens that have a high VTE risk.
KW - lenalidomide
KW - multiple myeloma
KW - survivorship
KW - thromboprophylaxis
KW - venous thromboembolism
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U2 - 10.1002/cncr.32682
DO - 10.1002/cncr.32682
M3 - Article
C2 - 31913498
AN - SCOPUS:85077902284
VL - 126
SP - 1640
EP - 1650
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 8
ER -