Treatment for Multiple Myeloma
Lenalidomide has substantially greater myelosuppression but less neuropathy than seen with thalidomide; however, both have the same tendency for DVT.[5,32,33] DVT prophylaxis with 81 mg of aspirin has been proposed, but randomized clinical trials have not confirmed any benefit for this recommendation.
- A prospective randomized trial (VISTA) of 682 previously untreated symptomatic patients who were not candidates for stem cell transplantation 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 26 months, the OS favored the bortezomib arm in the 3-year OS rates (72% vs. 59%, P = .03).[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.[8,34,35,36]
- 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 mo vs. 6.5 mo, P < .001) and in OS (82% vs. 75%, P = .05).[Level of evidence: 1iiA]
When bortezomib was incorporated with induction therapy, patients with unfavorable molecular cytogenetics did not show any difference in PFS or OS compared with patients with more favorable risk factors. The benefit from bortezomib appears to be maintained across risk groups.[38,39,40,41][Level of evidence: 3iiiD]
Because bortezomib is metabolized and cleared by the liver, it appears active and well tolerated in patients with renal impairment.
The VAD regimen has shown activity in previously treated and in untreated patients with response rates ranging from 60% to 80%.[42,43,44,45][Level of evidence: 3iiiDiv]
- No randomized studies support the widespread use of this regimen in untreated patients.
- This regimen avoids early exposure to alkylating agents, thereby minimizing any problems with stem cell collection (if needed) and any future risks for myelodysplasia or secondary leukemia.
- Disadvantages include the logistics for a 96-hour infusion of doxorubicin and a low complete response rate.
- An alternative version of VAD substitutes pegylated liposomal doxorubicin for doxorubicin, eliminates the need for an infusion, and provides comparable response rates.[46,47][Level of evidence: 3iiiDiv]
Evidence is not strong that any alkylating agent is superior to any other. All standard doses and schedules produce equivalent results. The two most common regimens historically have been oral MP and oral cyclophosphamide plus prednisone.[48,49,50]