The results of a study comparing the outcomes of multiple myeloma patients receiving Velcade as part of their initial therapy suggest that certain chromosomal abnormalities influence patient responses to Velcade.  The results also indicate that Velcade may be particularly effective in delaying progression of myeloma in patients with chromosomal abnormalities.

The findings were presented at the European Hematology Association (EHA) meeting in Barcelona, Spain.

The study aimed to shed light on the controversial issue regarding appropriate initial therapy regimens, also known as induction therapy, for multiple myeloma patients with high-risk chromosomal abnormalities.

“It is of paramount importance [to identify a patient’s chromosomal abnormalities prior to starting induction therapy]. The goal is to tailor therapy according to the [genetic] profile of the single patient,” wrote Dr. Michele Cavo, the study’s lead investigator, in an email to The Myeloma Beacon.

Multiple myeloma patients with high-risk chromosomal abnormalities have a poorer prognosis.  They often do not respond as well to treatment, and survival is poorer as compared to patients without these abnormalities.  However, previous studies have shown that patients with and without chromosomal abnormalities generally respond similarly to Velcade ^[1] (bortezomib) treatment.

To further investigate this issue, researchers analyzed the complete response and progression-free survival rates of 587 newly diagnosed patients who received Velcade as part of their upfront therapy. Progression-free survival refers to the percentage of patients who are alive and have not experienced disease progression a given length of time after the start of treatment.

Patients received one of three regimens: Velcade-thalidomide ^[2] (Thalomid)-dexamethasone ^[3] (Decadron), Velcade-melphalan ^[4] (Alkeran)-prednisone ^[5], or Velcade-melphalan-prednisone-thalidomide.  Patients were also evaluated for chromosomal abnormalities and considered to be high-risk if certain abnormalities were identified.

Researchers found that there was no statistically significant difference in the complete response rates between patients with or without high-risk chromosomal abnormalities (38 percent and 33 percent, respectively).  Furthermore, the predicted progression-free survival rates at 30 months post-treatment were nearly identical for both groups, 62 percent for high-risk patients compared to 66 percent for patients without chromosomal abnormalities.

High-Risk Subgroups

Differences in Velcade activity were observed, however, when researchers further divided the high-risk patients into two distinct subgroups: those with del(13q) and those with t(4; 14), and/or del(17p).

del(13q)

Thirty percent of the study participants carried a deletion occurring in chromosome 13. This portion of the chromosome is known to produce proteins that suppress myeloma cell production, and its deletion causes the continuous growth of cancerous cells.  Patients with this abnormality have poorer prognoses and sometimes become resistant to treatment.

This study revealed that after induction therapy containing Velcade, patients with del(13q) alone had a significantly higher complete response rate (47 percent) than patients with no chromosomal abnormalities (33 percent).  The predicted progression-free survival rate at 30 months post-treatment, however, was similar in both groups, 64 percent for patients in the del(13q) subgroup compared to 66 percent for patients without chromosomal abnormalities.

t(4;14) and del(17p)

Twenty-four percent of the participants were identified with translocations between chromosomes 4 and 14 and/or a deletion within chromosome 17.  Both of these defects lead to enhanced cell proliferation and survival, which contribute to cancerous cell growth.

In this subgroup, researchers directly compared the response in patients with only the t(4;14) mutation to patients with only the del(17p) mutation.  Patients with the del(17p) mutation had a lower chance of achieving a complete response (28 percent) than their t(4;14) carrying counterparts (48 percent).  In contrast, the predicted progression-free survival rate at 30 months post-treatment was similar for both groups, 66 percent for del(17p) and 69 percent for t(4;14).

The results show that in terms of complete response rates, patients with del(17p) may not respond to Velcade as well as other patients.  However, progression-free survival among all groups was similar.

Although the researchers acknowledged that the results of their study are consistent with previous reports that high-risk patients respond similarly to Velcade as patients without chromosomal abnormalities, at least in terms of progression-free survival, they urged that their results be cautiously interpreted.

They recommended that further studies comparing patients receiving the same Velcade-based treatment regimen be conducted in order to “draw firm conclusions about the ability of Velcade-based regimens to overcome the adverse prognosis related to the presence of t(4;14) and/or del(17p).”

In fact, Dr. Cavo stated that with additional studies, “I would be able to collect data from several European Cooperative groups in order to verify the impact of the same treatment regimen on the outcome of patients stratified according to different [chromosomal] abnormalities.”

For more information, see abstract ^[6] 1906 on the EHA meeting ^[7] website.