Velcade, known by its generic name bortezomib, is a targeted cancer therapy. It belongs to a class of drugs called proteasome inhibitors. Cells use a system called the proteasome to break down and recycle unwanted proteins. Velcade blocks these proteasomes, disrupting processes inside cancer cells and leading to their death. Myeloma cells are more sensitive to this disruption than normal cells, and the U.S. Food and Drug Administration (FDA) has approved Velcade for treating multiple myeloma and mantle cell lymphoma.
Defining Treatment Success
Researchers measure success in clinical trials using standardized metrics to evaluate how well a therapy works. The Overall Response Rate (ORR) calculates the percentage of patients whose cancer shrinks in response to treatment. Within this metric, a Complete Response (CR) means all signs of cancer have disappeared, while a Partial Response (PR) indicates a significant decrease in the amount of cancer, though it has not been completely eliminated.
Other metrics focus on the duration of the effect. Progression-Free Survival (PFS) measures how long patients live with the disease without it worsening, and Overall Survival (OS) is the total length of time a patient lives after starting treatment.
Efficacy in Newly Diagnosed Multiple Myeloma
For newly diagnosed multiple myeloma (NDMM), Velcade is a foundational treatment almost always administered as part of a combination therapy. This multi-drug approach improves the depth of response and prolongs the time until the disease progresses.
Common regimens include VMP, which combines Velcade with melphalan and prednisone. Another frequently used combination is VRd, which pairs Velcade with lenalidomide and dexamethasone. The choice of regimen depends on factors like a patient’s eligibility for a stem cell transplant.
The VISTA clinical trial provided significant evidence for Velcade’s efficacy in this setting, evaluating the VMP combination in newly diagnosed patients ineligible for stem cell transplant. The results showed a significantly higher overall response rate for the Velcade-based regimen compared to the control group. Patients receiving the Velcade combination also achieved a longer time before their disease progressed, and the median Progression-Free Survival was extended, establishing Velcade-based combinations as a standard of care for this patient group.
Efficacy in Relapsed or Refractory Multiple Myeloma
Velcade is also used for patients whose multiple myeloma has returned, known as “relapsed” disease, or for “refractory” myeloma, which is cancer that has stopped responding to treatment. This setting presents a greater challenge, as the cancer cells may have become more resistant to previous therapies.
In this context, Velcade can be used by itself (as a monotherapy) or in different combination regimens, such as with dexamethasone. The FDA has also approved retreatment with Velcade for patients who had previously responded to it and relapsed at least six months after finishing the prior treatment.
The APEX trial demonstrated Velcade’s effectiveness in patients with relapsed or refractory multiple myeloma. In this trial, Velcade as a single agent was compared to high-dose dexamethasone. Patients treated with Velcade had a significantly higher overall response rate.
The time to disease progression was longer for the Velcade group, and they also had a superior overall survival rate. This demonstrated that Velcade could extend the lives of patients in this difficult-to-treat population, establishing it as a standard of care.
Factors Influencing Individual Outcomes
While clinical trial data provides statistics on how groups respond to treatment, individual outcomes can vary. Several factors can influence how effective Velcade may be for a specific person.
A patient’s overall health, or performance status, is a factor, as individuals who are more fit may tolerate treatment better. Kidney function is another consideration, as multiple myeloma can affect the kidneys. Studies have shown that Velcade can be used safely and effectively even in patients with renal impairment.
The specific genetic features of the myeloma cells, known as cytogenetics, also play a large part in treatment response. Some genetic abnormalities, like deletion 17p (del(17p)), are considered “high-risk” and can make the cancer more aggressive. Velcade-based treatments can help improve outcomes even in patients with certain high-risk chromosomal abnormalities.