What is the efficacy of melphalan and prednisone (MP) therapies for the treatment of multiple myeloma (MM)?

Updated: May 11, 2021
  • Author: Dhaval Shah, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Subsequent research examined the use of regimens that combine MP with other agents. A randomized three-arm study compared MP, MP plus thalidomide, and reduced-intensity ASCT using melphalan 100 mg/m2 in 447 previously untreated patients between ages 65 and 75 years. After a median follow-up of 51.5 months, median overall survival (the primary endpoint) was significantly better in the MPT arm than in the other two arms: 51.6 months for MP plus thalidomide versus 33.2 months for MP and 38.3 months for transplantation arm. The authors recommended MPT as first-line treatment for previously untreated elderly patients with multiple myeloma. [68]  

Hulin et al conducted a randomized, placebo-controlled, phase III trial to investigate the efficacy of adding thalidomide to MP in 229 elderly patients (>75 y) newly diagnosed with MM. [69] During each 6-week cycle, melphalan 0.2 mg/kg/d plus prednisone 2 mg/kg/d was given to all patients on days 1-4 for 12 cycles. In addition, patients were randomly assigned to receive thalidomide 100 mg/d PO (n = 113) or placebo (n = 116), continuously for 72 weeks.

Overall survival was significantly longer in the group that received thalidomide (median, 44 mo) compared with placebo (median, 29.1 mo). [69] PFS was also significantly prolonged in the thalidomide group (median, 24.1 mo) relative to the placebo group (median, 18.5 mo). However, the investigators noted peripheral neuropathy and neutropenia were significantly increased in the thalidomide group. [69]

A randomized, controlled trial evaluated the addition of thalidomide to standard MP chemotherapy in elderly patients with previously untreated MM. Although no impact on survival was observed, more patients in the thalidomide group achieved an objective response. Of note, thromboembolic events were not more frequent in the thalidomide group. [70]  A separate study by Fayers et al concluded that thalidomide added to MP therapy improved overall survival and PFS in previously untreated elderly patients with MM, extending the mean survival time by an average of 20%. [71]  

MP plus lenalidomide has also shown promise. [72]  A study by Gay et al assessed the addition of thalidomide and/or bortezomib to standard oral MP treatment in 1175 elderly patients with newly diagnosed myeloma. [73] The study found that these novel agents helped achieve maximal response in these patients.

A phase III study by the ALCYONE Trial Investigators found that the addition of daratumumab to the combination of bortezomib, melphalan, and prednisone in patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation resulted in a lower risk of disease progression or death. [74] At a median follow-up of 16.5 months, results of treatment with and without daratumumab were as follows:

  • 18-month PFS rate: 71.6% vs 50.2% 
  • Overall response rate: 90.9% vs 73.9% (P< 0.001)
  • Rate of complete response or better (including stringent complete response): 42.6% 24.4% (P< 0.001)

However, the rate of grade 3 or 4 infections was 23.1% in the daratumumab group and 14.7% in the control group.

The MAIA trial was an open-label, randomized, phase 3 study comparing lenalidomide with low-dose dexamethasone with or without daratumumab in patients with newly diagnosed multiple myeloma ineligible for ASCT. The study demonstrated an improvement in PFS in the daratumumab combination arm compared with the control arm. Patients with a complete response or better was 47.6% in the daratumumab group and 24.9% in the control group. A total of 24.2% of the patients in the daratumumab group, as compared with 7.3% of the patients in the control group, had results below the threshold for minimal residual disease (1 tumor cell per 105 white cells). [75]

Current National Comprehensive Cancer Network (NCCN) guidelines recommend MP in combination with daratumumab and bortezomib as a category 1 regimen. However, the NCCN lists the following as preferred primary therapy regimens for non-transplant candidates [2] :

  • Bortezomib/lenalidomide/dexamethasone (category 1)
  • Daratumumab/lenalidomide/dexamethasone (category 1)
  • Lenalidomide/low-dose dexamethasone (category 1)
  • Bortezomib/cyclophosphamide/dexamethasone (preferred for patients with acute kidney injury)

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