Velcade Clinical Studies - Bortezomib Clinical Studies - Myeloma


What have Velcade clinical studies shown?

Clinical studies have shown that Velcade® (bortezomib, Takeda Oncology) is effective as initial therapy in myeloma, as maintenance therapy, and as therapy for previously treated myeloma.

Is Velcade-dex effective in previously untreated myeloma?

Velcade clinical studies suggest that Velcade-dex is an effective initial therapy for patients with myeloma, including patients who are eligible for high-dose chemotherapy and stem cell transplant and those who are not.

  • Velcade and dexamethasone is more effective than the once commonly used VAD (vincristine, Adriamycin®, and dexamethasone) therapy as upfront treatment for multiple myeloma in patients eligible for transplant, according to data from a large Phase III clinical trial.
  • Velcade-dex resulted in good response rates in the Phase III UPFRONT trial, which compared the safety and efficacy of three Velcade-based regimens in patients who were not eligible for stem cell transplant.

Is Velcade-Revlimid-dex effective in previously untreated myeloma?

Revlimid® (lenalidomide, Celgene) is thought to make myeloma cells more sensitive to Velcade and dexamethasone. The combination of Velcade, Revlimid, and dexamethasone (VRD or RVD) has been shown to be very effective as frontline therapy, with unprecedented activity seen, even in patients with high-risk features. In some cases, a lower dose of dexamethasone is used and the combination is referred to as VRd or RVd

  • For example, data from a large Phase III study (SWOG S0777) in patients with previously untreated myeloma showed that the addition of Velcade to Revlimid-low-dose dexamethasone (Rd) improved survival.
    • The study included 525 patients, including those who were transplant-eligible and those who were not transplant candidates. All patients received Rd maintenance until their disease progressed or they experienced unacceptable toxicity
    • Patients receiving VRd experienced a significantly longer time before disease progression (progression-free survival, PFS) compared to Rd (43 vs. 30 months)
    • Overall survival was significantly longer in patients receiving VRd compared to Rd (75 vs. 64 months).
  • Performing a stem cell transplant early after VRd induction therapy was shown to improve progression-free survival over VRd induction alone in a large Phase III study (IFM/DFCI 2009).
    • The study included 700 newly diagnosed patients who were eligible for stem cell transplantation. All received VRd induction and half also received an autologous stem cell transplant. All patients then received Revlimid maintenance for 1 year.
    • On average, patients who received a transplant experienced longer PFS (43 vs 34 months) and the percentage of patients surviving without disease progression at 4 years was significantly higher (47% vs. 35%).
    • Among responding patients in either treatment arm, PFS was significantly longer in those who had no evidence of remaining myeloma cells present in the bone marrow (minimal residual disease, MRD) before and after maintenance therapy as detected by very sensitive tests.
    • Patients on this study continue to be followed to determine the effect of transplant on overall survival.

VRD is included in myeloma treatment guidelines as one of several preferred options for initial therapy for transplant candidates, and is one of the most commonly used regimens in transplant candidates in the United States. VRD is also one of several preferred options for treating myeloma in patients who are not transplant candidates.

Is Velcade-Cyclophosphamide-dex effective in previously untreated myeloma?

The addition of the chemotherapy agent cyclophosphamide to Velcade-dex has been shown to improve response rates. Velcade-cyclophosphamide-dex (CyBorD or VCD) is one of several preferred options for frontline therapy in transplant candidates listed in current treatment guidelines. This recommendation is based on the high response rates and rapid responses seen in three phase II trials:

  • Results of a German trial show CyBorD to be an effective frontline regimen in patients 60 years or younger, and also in those patients with high-risk myeloma. An overall response rate (partial response or better) of 84% was seen, and 10% of patients achieved a complete response.
  • A North American trial of CyBorD induction showed a similar overall response rate (88%) and a complete/near-complete response rate of 39%, which was improved to 70% following transplant.
  • The use of frontline Velcade, dexamethasone, and weekly cyclophosphamide in a US study achieved high response rates and rapid responses, with 53% of patients achieving a very good response or better. An overall response rate of 100% was seen, and at 1 year, no patients had progressed.

CyBorD is also used as initial treatment in patients who are not eligible for transplant.

Is Velcade effective as maintenance therapy?

Velcade is sometimes used as maintenance therapy following stem cell transplantation or other therapy as a way to reduce the risk of relapse and extend survival. Results of several Phase III trials show that maintenance therapy with weekly Velcade can improve outcome. For example:

  • Velcade maintenance increased response rates in elderly transplantation-ineligible patients who received a variety of Velcade-based frontline regimens.
  • Velcade-based maintenance regimens improved the quality of response in older patients with myeloma.

Velcade maintenance given every other week for up to 2 years following stem cell transplantation has also been shown to be well tolerated and associated with improvement in response rates and survival, including in patients with poor-risk genetic features, according to results of a Phase III trial conducted in Europe.

The potential benefits of Velcade maintenance therapy must be balanced with the potential toxicity associated with long-term use of Velcade.

Is Velcade effective in treating relapsed and/or refractory myeloma?

Velcade is used in the treatment of relapsed and/or refractory myeloma.

Data from a large Phase III clinical trial showed that Velcade was more effective than high-dose dexamethasone (a standard of care at that time). Compared with patients treated with high-dose dexamethasone, patients treated with Velcade had:

  • a significantly longer time-to-disease progression (TTP)
  • higher response rates
  • improved survival

What Velcade combination therapies are effective in relapsed and/or refractory myeloma?

Velcade is commonly used as part of combination therapy for the treatment of relapsed and/or refractory myeloma. Recent clinical trials have shown that treatment with some of these Velcade combinations have resulted in high response rates and improved disease-free survival. Examples include:

  • Velcade and Dexamethasone: is often added to Velcade therapy as it has been shown to improve response rates over that seen with Velcade alone.
  • Velcade, Revlimid, and Dexamethasone: Results from a multicenter Phase II trial show that the three-drug combination is very effective as a treatment for relapsed or refractory myeloma. As a result, VRD is often used in this setting and is listed as one of several preferred options for treatment of relapsed or refractory myeloma in current treatment guidelines.
    • Overall, 64% of 64 evaluable patients responded to this treatment (a partial response or better) and 25% achieved a complete or near-complete response.
    • After a median follow-up of almost 36 months, overall survival was encouraging and approached 30 months, and 45% of patients were still alive.
    • The combination was well tolerated, with manageable side effects.
  • Velcade, Cyclophosphamide, and Dexamethasone (VCD): The addition of cyclophosphamide to Velcade-dex has been shown to improve response rates.
  • Velcade and Doxil: Doxil® (doxorubicin HCl liposome injection, Janssen) is approved for use in combination with Velcade to treat relapsed and refractory myeloma patients who have not previously received Velcade and who have received at least one prior therapy. Results from a Phase III clinical trial show that patients treated with Velcade and Doxil were disease-free significantly longer (a median time of 9.3 months) than patients treated with Velcade alone (a median time of 6.5 months).
  • Velcade, Farydak, and dex: Farydak® (panobinostat, Novartis) is approved for use in combination with Velcade and dexamethasone to treat patients with myeloma who have received at least 2 other treatments, including Velcade and an immunomodulatory agent (Revlimid, Thalomid® [thalidomide, Celgene], or Pomalyst® [pomalidomide, Celgene]). Results from a Phase III clinical trial show that patients treated with Velcade, Farydak, and dex were disease-free significantly longer than the patients treated with Velcade-dex (a median time of 12 months vs 8.1 months).

Velcade retreatment remains a highly effective therapeutic option for previously treated myeloma. According to an analysis of 23 studies that included a total of 1051 patients, retreatment with Velcade-based therapy was effective and well-tolerated in patients with relapsed/refractory myeloma. The overall response rate to Velcade retreatment across all studies was 39%.

What other Velcade combination therapies are being evaluated in myeloma?

There are many other Velcade combination therapies being evaluated in ongoing clinical trials in myeloma. Some combinations include conventional chemotherapy agents, while others include new novel therapies. For example, the following combinations are being tested in Phase III trials in relapsed and/or refractory myeloma:

  • Velcade-low-dose dex plus Darzalex® (daratumumab, Genmab), a monoclonal antibody that binds to the CD38 marker on myeloma cells.
  • Velcade-low-dose dex and Pomalyst

The combination of Velcade, Revlimid, and low-dose dex (VRd) is also being evaluated alone and in combination with high-dose chemotherapy and autologous stem cell transplant in a Phase III trial in newly diagnosed myeloma. Results from this trial will help determine if transplant is still necessary in the initial management of myeloma in younger patients or whether novel agents alone provide similar outcomes.

Interested in learning more about Velcade clinical trials? Talk to an MMRF Patient Support Nurse to learn more or use our clinical trials finder: