ORIGINAL ARTICLE
Phase 2 Study of Pegylated Liposomal Doxorubicin, Vincristine, Decreased-Frequency Dexamethasone, and Thalidomide in Newly Diagnosed and Relapsed-Refractory Multiple Myeloma

https://doi.org/10.4065/81.7.889Get rights and content

OBJECTIVE

To evaluate the efficacy and safety of adding thalidomide to the pegylated liposomal doxorubicin, vincristine, and decreased-frequency dexamethasone (DVd) regimen for multiple myeloma.

PATIENTS AND METHODS

Patients newly diagnosed as having active multiple myeloma and those with relapsed-refractory disease were studied between August 2001 and October 2003. Patients received DVd as previously described. Thalidomide was given at 50 mg/d orally and the dose increased slowly to a maximum of 400 mg/d. At the time of best response, patients received maintenance prednisone, 50 mg orally every other day, and daily thalidomide at the maximum tolerated dose for each patient. The primary end point was the rate of complete responses plus very good partial responses as defined by the European Group for Blood and Marrow Transplantation criteria and the Intergroupe Français du Myélome, respectively.

RESULTS

Of 102 eligible patients, 53 were newly diagnosed as having multiple myeloma, and 49 had been previously treated for multiple myeloma. The complete response plus very good partial response rate was 49% and 45%, with an overall response rate of 87% and 90% for patients with newly diagnosed and previously treated multiple myeloma, respectively. Furthermore, better responses were associated with improved progression-free and overall survival. The most common grade 3 and 4 adverse events were thromboembolic events (25%), peripheral neuropathy (22%), and neutropenia (14%).

CONCLUSIONS

The addition of thalidomide to the DVd regimen significantly improves the response rate and quality of responses compared with the DVd regimen alone. This improvement is associated with longer progression-free and overall survival. The rate of observed quality responses is comparable to responses seen with high-dose therapy.

Section snippets

PATIENTS AND METHODS

Eligibility criteria included age older than 18 years, active multiple myeloma with a measurable serum or urine paraprotein level, and ability to understand and sign an informed consent document. Active multiple myeloma was defined by evidence of end-organ damage related to the plasma cell disease.18 Patients had to have an Eastern Cooperative Oncology Group performance status of 0 to 2, a serum bilirubin level less than 2 times the upper limit of normal, serum alanine aminotransferase and

Patient Characteristics

One hundred five patients were enrolled in the trial. Three patients did not complete at least one cycle and were not evaluable for response but were evaluable for toxic effects. The 102 patients who completed at least one cycle included 53 with newly diagnosed disease and 49 with relapsed-refractory disease. The median age for all patients was 63 years (IQR, 53-69 years), 56% were male, and 79% were white. The SWOG staging for all patients was as follows: 25%, 46%, 4%, and 25% had stages I,

DISCUSSION

Despite the addition of various chemotherapeutic agents and the trials of high-dose therapy with supportive autologous stem cell transplantation, multiple myeloma continues to be an incurable disease.27 The DVd regimen, with a better tolerability and ease of administration, does not result in high-quality responses or survival advantages when compared with traditional regimens.7, 8 In this study, we show that the addition of thalidomide to the DVd regimen not only improves the response rate but

CONCLUSIONS

Adding thalidomide to the DVd regimen improved the response rate and the quality of response in patients with multiple myeloma comparable to what is achieved with high-dose therapy. The improved quality of response (CR plus VGPR) was associated with improved outcome as measured by PFS and OS. The high rate of CR plus VGPR makes this regimen an attractive induction chemotherapy regimen for patients with newly diagnosed multiple myeloma before proceeding with high-dose therapy and stem cell

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    This study was supported in part by a research grant from Celgene Corporation, Ortho Biotech, The Myeloma Foundation, and The Pastore Foundation.

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