Venous thromboembolism risk with contemporary lenalidomide-based regimes for multiple myeloma: A systematic review and meta-analysis.

person Rajshekhar Chakraborty Cleveland Clinic, Cleveland, OH info_outline Rajshekhar Chakraborty, Irbaz Bin Riaz, Saad Malik, Naimisha Marneni, Alex Mejia Garcia, Faiz Anwer, Alok A. Khorana, S. Vincent Rajkumar, Shaji Kumar, M. Hassan Murad, Zhen Wang, Safi U. Khan, Navneet S. Majhail

Authors person Rajshekhar Chakraborty Cleveland Clinic, Cleveland, OH info_outline Rajshekhar Chakraborty, Irbaz Bin Riaz, Saad Malik, Naimisha Marneni, Alex Mejia Garcia, Faiz Anwer, Alok A. Khorana, S. Vincent Rajkumar, Shaji Kumar, M. Hassan Murad, Zhen Wang, Safi U. Khan, Navneet S. Majhail Organizations Cleveland Clinic, Cleveland, OH, Mayo Clinic, Rochester, MN, University of Arizona, Tuscon, AZ, Cleveland Clinic Foundation, Cleveland, OH, Cleveland Clinic- Taussig Cancer Institute, Cleveland, OH, West Virginia University, Morgantown, WV, Cleveland Clinic Taussig Cancer Institute and Case Comprehensive Cancer Center, Cleveland, OH Abstract Disclosures Research Funding Other Background: The risk of venous thromboembolic events (VTE) despite mandatory thromboprophylaxis (TPx) in patients with multiple myeloma (MM) receiving contemporary lenalidomide (Len)-based regimens is not well-defined. Methods: Medline, Embase, and CENTRAL databases were queried to identify phase 1-3 clinical trials of Len-based regimens with mandatory TPx published until April 2018. Random effects meta-analysis was performed using CMAv3 software to obtain crude, and per 100 patient-cycle incidence rate (IR). Prespecified subgroup analyses were performed to obtain IR for VTE by (1) line of treatment (newly diagnosed [ND], relapsed/refractory [RR] and maintenance [Mx] phase) and (2) different Len-based regimens. Results: We screened 1069 citations and analyzed data from 43 trials with 8696 patients, including 17 in ND, 23 in RR and 3 in Mx phase. 12 out of 43 were Phase 3 randomized controlled trials. The overall incidence of VTE in 8696 patients was 4.6% (95% CI, 3.7-5.8%), with 1.0 event (95% CI, 0.7-1.4%) per 100 patient cycles. In patients with NDMM (n = 3295), 193 (5.9%) experienced VTE with a pooled IR of 0.9 (95% CI, 0.3-2.3) per 100 patient-cycle. Among RRMM patients (n = 3981), 251 (6.3%) experienced VTE with a pooled IR of 1.0 (95% CI, 0.4-2.3) per 100 patient-cycle. The incidence of VTE was highest with the following triplet regimens: Rd + Proteasome inhibitor (PIs) and Rd + Anthracycline (Ac) [+/- Vincristine], with the latter having a high risk of VTE regardless of the treatment phase (table). With Len Mx (n = 1420), 38 (2.7%) patients had VTE, with a pooled IR of 0.2 (95% CI, 0-2.1) per 100 patient-cycle. Conclusions: Patients with MM undergoing treatment with Len-based regimens remain at risk of VTE despite current TPx strategies. The estimates of VTE IR provided by this analysis can guide clinicians in assessing treatment-related risk of VTE in this setting. Regimen No. of trials No. of Patients VTE event/100 patient-cycle 95% CI NDMM Rd 3 1320 0.1 0.0-0.8 Rd + PI 5 237 2.2 0.9-5.3 MPR/CPR 5 1246 0.2 0.1-1.0 Rd + Anthracycline (Ac) 2 247 1.4 0.4-4.3 RRMM Rd 7 1760 0.2 0.1-0.8 Rd + PI 6 966 0.5 0.2-1.5 Rd + Monoclonal Antibodies 3 661 0.3 0.0-5.6 Rd + Ac +/- Vincristine 3 207 2.0 0.7-5.4 Mx Len 3 1420 0.2 0.0-2.1