A group of international researchers analyzed the outcomes of multiple myeloma patients after they failed to respond to therapy with novel agents, such as Velcade, Revlimid, and thalidomide.

The study authors stated that the results will help physicians and patients better understand patients’ prognoses and select appropriate clinical trials.

“The study provides an estimate of the expected outcome among patients with myeloma that has stopped responding to the newly available drugs,” said Dr. Shaji Kumar from the Mayo Clinic in Minnesota and lead author of the study. “This will allow patients to compare available options and specifically evaluate clinical trial options.”

Since multiple myeloma remains incurable, the researchers involved with this study explained that it is important to be able to determine which treatments in early phases of clinical development are the most promising.

Most treatments under clinical development are first tested in relapsed and refractory (resistant) myeloma patients.  To better understand which of these treatments are the most promising, the researchers argued that it would be useful to better understand what treatments patients receive after they fail on current novel agents and how they respond to those treatments. They explained that these results could then be used as a benchmark against which the results for treatments under development could be compared to identify the most promising ones. For example, treatments under development with results inferior to the benchmark would no longer be considered promising.

The researchers, who were part of the International Myeloma Working Group, an international group of top myeloma experts, therefore, retrospectively studied medical records of 286 patients from the United States, Europe, and Asia, who did not respond to Velcade ^[1] (bortezomib) and also relapsed on, did not respond to, or were unable to take Revlimid ^[2] (lenalidomide) or thalidomide ^[3] (Thalomid).  The researchers analyzed the records to identify the therapies that were used after the patients failed novel agent therapy as well as response and survival rates for these patients.

The researchers found that 74 percent of patients included in the study continued to receive treatment after becoming non-responsive to novel agents. For the first treatment regimen used after novel agent failure, 26 percent of regimens included Velcade, 19 percent included Revlimid, and 14 percent included thalidomide.

Dr. Kumar explained that a fraction of patients continued to receive novel agent therapy after having failed on these therapies because patients sometimes respond to combinations of these drugs, for example Velcade plus Revlimid, even after failing to respond to individual novel agents.

Response rates to this first regimen included 2 percent complete response, 5 percent very good partial response, and 17 percent partial response. Additionally, overall response rates were the same for patients who received a novel agent-based regimen and those who did not receive a novel agent.

Of the patients who received two or more different treatment regimens after initially failing on novel agents, 35 percent received Velcade, 30 percent received Revlimid, and 24 percent received thalidomide. Additionally, 15 percent of patients received a stem cell transplant after failing novel agent therapy.

Overall response rates were 19 percent after two regimens, 24 percent after three regimens, 22 percent after four regimens, and 6 percent after five regimens following failure to respond to novel agents.

Dr. Kumar said that after patients fail on novel agent therapy, they are most likely to respond to older drugs, such as melphalan ^[4] (Alkeran), cyclophosphamide ^[5] (Cytoxan), and doxorubicin ^[6] (Adriamycin), especially when used in combination with some of the newer drugs.

The median event-free survival was five months and the median overall survival was nine months once patients failed to respond to novel agents. Patients who received treatment after becoming non-responsive had a median overall survival of 12 months, while patients who did not receive further treatment had a median overall survival of three months.

Median overall survival was 11 months from the time patients failed Velcade therapy. Median overall survival was 22 months from the time patients relapsed on, failed, or were unable to tolerate Revlimid and 16 months for thalidomide.

The researchers also determined that high beta-2 microglobulin and low albumin levels in the blood after failing novel agent therapy were strong predictors of poor overall survival.

For more information, please see the article in Leukemia ^[7] (abstract).