Randomized Trials Needed to Determine Benefit of Thromboprophylaxis in Patients With Multiple Myeloma Receiving Thalidomide- or Lenalidomide-Based Regimens

ORLANDO, Fla.—Patients with newly diagnosed or previously treated multiple myeloma (MM) who receive thalidomide (T)- or lenalidomide (L)-based regimens are at high risk of venous thromboembolism (VTE), and it is uncertain whether thromboprophylaxis provides a clear benefit, especially in those who receive L-based therapy or have previously treated disease, results of a systematic review and meta-analysis have found.

These findings call for randomized controlled trials to address this important clinical need, Marc Carrier, MD, MSc, of University of Ottawa, Ottawa, Ontario, Canada, and colleagues reported in a poster presentation during the 52nd American Society of Hematology Meeting and Exposition.

The investigators noted that consensus guidelines recommend routine thromboprophylaxis, and recent observational studies have suggested the efficacy of thromboprophylaxis in decreasing VTE risk in this population; however, reliable data from randomized controlled trials are lacking. Therefore, the investigators sought to determine absolute rates of VTE with and without thromboprophylactic agents, including ASA, warfarin, and low-molecular-weight heparin (LMWH), in patients with newly diagnosed or previously treated MM who received T- or L-based regimens.

A systematic literature search using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, and all EBM Reviews of published studies up to January 2010 was conducted; 66 studies were included in the analyses. Of these, 61 studies (4264 patients) assessed T-based regimens and 5 (1119 patients), L-based regimens.

Rate of VTE (per 100 patient-cycles) in patients with newly diagnosed MM treated with T alone was 1.3 (95% CI, 0.4-2.7) with no prophylaxis (n=380) compared with 0.5 (95% CI, 0.4-0.6) with prophylactic LMWH (n=64). For T plus dexamethasone (D), the rates were 4.1 (95% CI, 2.8-5.9) with no prophylaxis (n=628); 2.6 (95% CI, 2.1-3.2) with any prophylaxis (n=993); 2.3 (95% CI, 0.9-7.9) with ASA (n=80); 2.8 (95% CI, 2.0-3.9) with warfarin 1-1.25 mg/d (n=387); 2.1 (95% CI, 1.1-3.6) with prophylactic LMWH (n=446); and 1.6 (95% CI, 0.2-4.1) for therapeutic anticoagulation (n=80). Please click here for more study data.

Rate of VTE (per 100 patient-months) in patients with previously treated MM who received T plus D/cyclophosphamide including doxorubicin was 6.7 (95% CI, 0.5-18.9) for no prophylaxis (n=331) and 3.5 (95% CI, 1.2-6.5) with warfarin 1-1.25 mg/d (n=50). For those receiving TD/cyclophosphamide, the rate was 0.9 (95% CI, 0.3-1.8) with no prophylaxis (n=321); 2.4 (95% CI, 1.3-4.0) with warfarin 1-1.25 mg/d (n=102); and 0 (95% CI, 0-2.2) with therapeutic doses of anticoagulation (n=18). For all other treatment regimens, VTE rate was <1 with or without prophylaxis. Please click here for more study data.

For L-based regimens, rate of VTE (per 100 patient-cycles) in patients with newly diagnosed MM was 0.8 (95% CI, 0.07-2.0) with no prophylaxis (n=278); 0.7 (95% CI, 0.5-1.1) with any prophylaxis (n=349); and 0.9 (95% CI, 0.5-1.5) with ASA (n=172). In those with previously treated MM managed with L plus D, the rate was 0.7 (95% CI, 0.4-0.9) with no prophylaxis (n=361); in those who received LD/cyclophosphamide regimens that included doxorubicin, VTE rate was 0.6 (95% CI, 0.01-2.1) with ASA (n=131). Please click here for more study data.

The investigators noted limitations of the analyses included that the definition for VTE varied across all studies and most did not outline diagnostic criteria for VTE. In addition, data were not available for all prophylaxis regimens. None of the studies reported major bleeding events.