Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Treatment for Multiple Myeloma
Lenalidomide has substantially greater myelosuppression but less neuropathy than seen with thalidomide; however, both have the same tendency for DVT.[6,33,34,35] A randomized, prospective trial of 342 previously untreated patients receiving lenalidomide-containing regimens compared aspirin (100 mg/day) with enoxaparin (40 mg/day); the 2% incidence of venous thromboembolic events was similar for both interventions. Empirically, the greater the number of risk factors for DVT, the more intense the recommendation for prophylactic anticoagulation. (Refer to the Thalidomide section of this summary for more information about risk factors.)
A retrospective review of almost 4,000 relapsed or refractory patients who received lenalidomide in 11 clinical trials suggested an increased incidence of nonmelanoma skin cancers. As a result of predominant renal clearance, lenalidomide doses need to be reduced in the setting of impaired renal function (creatinine clearance, 30–50: 10 mg per day; creatinine clearance, <30: 15 mg every other day; dialysis, 15 mg on day after dialysis). Uncontrolled trials, including NCT00151203, have added clarithromycin (500 mg twice a day) to lenalidomide and dexamethasone with a claim of increased response rates; controlled studies are required to establish the value of this approach.
- Several phase I and II trials in heavily pretreated patients after bortezomib and lenalidomide showed a response rate ranging from 26% to 63%.[40,41,42][Level of evidence: 3iiiDiv] Although pomalidomide is taken orally like thalidomide and lenalidomide, pomalidomide causes less neuropathy and asthenia than thalidomide and less myelosuppression and skin rashes than lenalidomide.
- A prospective, randomized trial (the VISTA trial [NCT00111319]) of 682 previously untreated symptomatic patients who were not candidates for stem cell transplantation (SCT) because of age (one-third of patients >75 years) compared bortezomib combined with melphalan and prednisone with melphalan and prednisone alone.
- With a median follow-up of 60 months, the median OS favored the bortezomib arm (56.4 vs. 43.1 months, P < .001).[Level of evidence: 1iiA]
- A prospective, randomized study of 669 patients with relapsing myeloma, who had been treated previously with steroids, compared intravenous bortezomib with high-dose oral dexamethasone.
- With a median follow-up of 22 months, the median OS was 29.8 months for bortezomib versus 23.7 months for dexamethasone (HR, 0.77; P = .027), despite 62% of dexamethasone patients crossing over to receive bortezomib.[Level of evidence: 1iiA]
- Bortezomib-associated peripheral neuropathy is reversible in most patients after dose reduction or discontinuation.[9,44,45]
- A prospective, randomized trial (NCT00103506) of 646 previously treated patients compared bortezomib plus pegylated liposomal doxorubicin with bortezomib alone.
- With a median follow-up of 7 months, the combination was better in both median time to progression (9.3 months vs. 6.5 months, P < .001) and in OS (82% vs. 75%, P = .05).[Level of evidence: 1iiA]
- Two studies compared bortezomib plus thalidomide plus dexamethasone versus thalidomide plus dexamethasone after SCT and showed improved PFS (3-year PFS of 68% vs. 48% [P = .042] in previously untreated patients and median PFS of 20 months versus 14 months in relapsed patients [P = .001]) but no difference in OS.[47,48][Level of evidence: 1iiDiii]
- In 511 previously untreated patients not eligible for transplant and older than 65 years, a randomized comparison of bortezomib plus melphalan plus prednisone plus thalidomide plus subsequent maintenance used bortezomib plus thalidomide versus bortezomib plus melphalan plus prednisone (with no maintenance) and showed superiority of the arm with thalidomide and bortezomib during induction and maintenance.
- With a median follow-up of 47 months, 3-year PFS was 55% versus 33% (P < .01), and 5-year OS was 59% versus 46% (P = .04).[Level of evidence: 1iiA] Because of trial design, it is unclear whether the improved results were caused by the addition of thalidomide during induction or by the use of maintenance therapy with bortezomib and thalidomide.
- In 827 previously untreated patients, a randomized comparison of bortezomib plus doxorubicin plus dexamethasone followed by high-dose melphalan plus autologous SCT plus bortezomib maintenance for 2 years versus vincristine plus doxorubicin plus dexamethasone followed by the same SCT consolidation plus thalidomide maintenance showed superiority of the arm with bortezomib during induction and maintenance.[Level of evidence: 1iiDiii]
- With a median follow-up of 41 months, the median PFS was 35 months versus 28 months in favor of the bortezomib arm (P = .002) with no significant difference in OS.