Based on it's effectiveness in treating patients with relapsed and refractory myeloma, Velcade, alone (sometimes called "monotherapy" or "single-agent") and in combination with other commonly used treatments, is being studied as therapy for previously untreated patients (sometimes called "frontlin" or "upfront" therapy). Data from some of these studies show consistently high response rates, including some of the highest recorded response rates for upfront treatment of myeloma.

• Data from a Phase II clinical trial of 44 previously untreated, high-risk patients (ie, patients with beta-2 microglobulin ≥5.5, plasma cell labeling index ≥1, a chromosome 13 deletion) show that 43% of the evaluable patients treated with Velcade had a partial response or better.¹ Median progression-free survival was 9.4 months for these patients.


• Long-term results from a separate clinical trial of 50 patients treated with Velcade compared with Velcade and dexamethasone showed the combination is highly active as a frontline therapy.² Patients received up to six Velcade treatment cycles and dexamethasone was given to those patients who had less than a partial response after two cycles or less than a complete response after four cycles. Ninety percent of patients had a partial response or better and 19% percent of patients achieved a complete or near-complete response.


• Velcade and dexamethasone is more effective than the once commonly used VAD (vincristine, Adriamycin, and dexamethasone) therapy as upfront treatment for multiple myeloma, according to data from 482 patients enrolled in a Phase III clinical trial.³ Twenty-one percent of patients treated with Velcade and dexamethasone had a complete response or near-complete response, compared with 8% of patients treated with VAD.

• Preliminary data from 42 of 66 patients enrolled in an ongoing Phase I/II clinical trial show 28% of patients treated with the combination of Velcade, Revlimid, and dexamethasone had a complete response or near-complete response and 98% of patients had a partial response or better.⁴

Results from several studies have shown that Velcade in combination with Thalomid and dexamethasone is effective in the treatment of previously untreated patients.

• Data from a Phase III clinical trial show that 36% of patients treated with Velcade, Thalomid, and dexamethasone had a complete response or near complete compared with 9% of patients treated with only Thalomid and dexamethasone.⁵ Furthermore, the enhancement of complete response or near complete response rates for patients treated with Velcade, Thalomid, and dexamethasone remained even after transplant (57% for Velcade, Thalomid, and dexamethasone versus 28% for Thalomid and dexamethasone).


• Data from a separate study of 38 previously untreated patients show that 16% of patients treated with three or fewer cycles of Velcade/Thalomid/Dexamethasone had a complete response and 87% had a partial response or better.⁶

The combination of Velcade and Doxil is approved for the treatment of relapsed and refractory multiple myeloma and is now being studied as frontline therapy.

• Final data from 29 of 57 previously untreated patients enrolled in a Phase II clinical trial show that 28% who received Velcade and Doxil had a complete response or near-complete response and 79% had a partial response or better.⁷


• Data from a Phase II clinical trial of 40 previously untreated patients show that 43% of patients who were treated with Velcade, Doxil, and dexamethasone had a complete response or near-complete response and 93% had a partial response or better.⁸ Data from this study also show that more patients treated with this combination had a complete response or better following transplantation compared to patients who had single or tandem transplants but were not treated with this combination.

• The combination of melphalan and prednisone (MP) has commonly been used as frontline therapy in patients who are ineligible for a stem cell transplant. Data from the large Phase III VISTA clinical trial, which enrolled 682 patients, show that adding Velcade to melphalan and prednisone significantly extends the length of time before disease progresses, the length of time a patient remains disease-free following treatment, and improves complete response rates and overall survival compared with patients treated with melphalan and prednisone alone.⁹


• A prior Phase I/II trial studying the addition of Velcade to the standard melphalan-prednisone combination in untreated elderly patients found that 32% of patients had a complete response and an additional 11% had a near complete response.¹⁰ These response rates are similar to those typically seen only in patients who had undergone stem cell transplantation.

For more information about additional clinical trials evaluating Velcade in the frontline setting, click here.

References

1. Dispenzieri A, Zhang L, Fonseca R, et al. Single agent bortezomib is associated with a high response rate in patients with high-risk myeloma. A phase II study from the Eastern Cooperative Oncology Group (E2A02). Blood. 2006;108(11). Abstract 3527.
2. Jagannath S, Durie BGM, Wolf JL, et al. Long-term follow-up of patients treated with bortezomib alone and in combination with dexamethasone as frontline therapy for multiple myeloma. Blood. 2006;108(11). Abstract 796.
3. Harousseau JL, Mathiot C, Attal M, et al. Velcade/Dexamethasone (Vel/D) versus VAD as induction treatment prior to autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma (MM): Updated results of the IFM 2005/01 trial. Blood. 2007;110(11). Abstract 450.
4. Richardson PG, Lonial, S, Jakubowiak S, et al. Safety and efficacy of lenalidomide (len), bortezomib (Bz), and dexamethasone (Dex) in patients (pts) with newly diagnosed myeloma: a phase I/II study. J Clin Oncol. 2008 (May 20 suppl). Abstract 8520.
5. Cavo M, Patriarco F, Tacchetti P, et al. Bortezomib (Velcade)-thalidomide-
   dexamethasone (VTD) vs thalidomide-dexamethasone (TD) in preparation for autologous stem cell (SC) transplantation (ASCT) in newly diagnosed multiple myeloma (MM). Blood. 2007;110(11). Abstract 73.
6. Wang M, Giralt S, Delasalle K, et al. Bortezomib in combination with thalidomide-dexamethasone for previously untreated multiple myeloma. Hematology. 2007;12:235-239.
7. Orlowski RZ, Peterson BL, Sanford B, et al. Bortezomib and pegylated liposomal doxorubicin as induction therapy for adult patients with symptomatic multiple myeloma: Cancer and Leukemia Group B Study 10301. Blood. 2006;108(11). Abstract 797.
8. Jakubowiak A, Al-Zoubi A, Kendall T, et al. Combination therapy with bortezomib (Velcade), Doxil, and dexamethasone (VDD) in newly diagnosed myeloma: updated results of a phase II clinical trial. Haematologica. 2007;92(6, suppl. 2). Abstract PO-721.
9. San Miguel JF, Schlag R, Khuageva N, et al. MMY-3002: a phase 3 study comparing bortezomib-melphalan-prednisone (VMP) with melphalan-prednisone (MP) in newly diagnosed multiple myeloma. Blood. 2007;110(11). Abstract 76.
10. Mateos MV, Hernandez JM, Hernandez MT, et al. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase1/2 study. Blood. 2006;108(7):2165-72.