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Carfilzomib Continues To Show Promising Results For Multiple Myeloma (ASH 2010)

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Published: Dec 5, 2010 6:00 pm

Carfilzomib continues to show promising results in multiple myeloma according to four studies presented in a poster session yesterday at the 2010 American Society of Hematology annual meeting in Orlando.

Carfilzomib (Kyprolis), developed by Onyx Pharmaceuticals, is a new drug that is currently being investigated as a potential treatment for multiple myeloma. It belongs to the same class of drugs as Velcade (bortezomib). However it works slightly differently by binding to different proteins than Velcade.

Recent research has indicated that carfilzomib is effective for patients with relapsed or refractory (resistant) myeloma who have received multiple prior treatments or have an advanced stage of disease (see related Beacon news).

“The carfilzomib posters confirm without a doubt that we have an active new drug for the treatment of myeloma,” said Dr. S. Vincent Rajkumar of the Mayo Clinic, who is not involved in the development of carfilzomib. “We are hopeful that the drug will be granted accelerated approval. Carfilzomib also has the possible added benefit of a lower neuropathy rate.”

The four studies presented yesterday showed results for specific patient groups treated with carfilzomib.

Single-Agent Carfilzomib In Patients Without Prior Velcade Treatment

In the Phase 2 trial PX-171-004, researchers evaluated the activity of carfilzomib in relapsed/refractory myeloma patients who received one to three prior treatments.

In a sub-analysis, the researchers investigated carfilzomib’s effects in 110 patients participating in the study who had not previously been treated with Velcade.

The researchers found that single-agent carfilzomib induced high response rates in these patients.

Many of the 110 patients had multiple existing illnesses: 53 percent had mild neuropathy (pain and tingling in the legs, feet, hands, and arms), 30 percent had kidney dysfunction, and 17 percent had diabetes. Many of these patients were also considered to have high-risk myeloma due to certain chromosomal abnormalities.

The patients were treated with 20 mg/m2 of carfilzomib on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for a maximum of 12 cycles. In some patients, the dosage of carfilzomib was increased to 27 mg/m2 after the first cycle. All patients also received 4 mg of dexamethasone (Decadron) in the first cycle only.

Researchers found that of 110 patients who had not received prior Velcade treatment, 48 percent responded to carfilzomib treatment. For patients who received the increased dosage of carfilzomib following cycle 1, the overall response rate was 54 percent.

The most common mild to moderate treatment-related side effects were fatigue (61 percent), nausea (43 percent), low red blood cell count (39 percent), shortness of breath (36 percent), cough (34 percent), headache (31 percent), low platelet count (30 percent), and upper respiratory infections (30 percent). None of the 110 patients discontinued treatment due to peripheral neuropathy.

Single-Agent Carfilzomib In Patients With Chromosomal Abnormalities

In a sub-analysis of a different Phase 2 trial (PX-171-0030A1), researchers evaluated the effect of chromosomal abnormalities on the response rates of relapsed/refractory myeloma patients who received single-agent carfilzomib .

The researchers found that the presence of unfavorable chromosomal abnormalities did not significantly impact that activity of single-agent carfilzomib in relapsed/refractory myeloma patients.

Previous research has indicated that certain chromosomal abnormalities are associated with a poorer prognosis for myeloma.

The 266 patients participating in the study had received a median of five prior treatments with a median of 13 different anti-myeloma drugs. Nearly all of the patients had been previously treated with Velcade. One third of the patients (31 percent) had at least one unfavorable chromosomal abnormality

The patients were treated with 20 mg/m2 of carfilzomib on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for a maximum of 12 cycles. After the first cycle, the dosage of carfilzomib was increased to 27 mg/m2.

Of the patients with at unfavorable chromosomal abnormalities, 28 percent responded to treatment compared to 24 percent of patients with favorable or no abnormalities.

Response lasted a similar length of time for both groups: 6 months in patients with unfavorable chromosomal abnormalities and 8 months for the remaining patients.

Long-Term Treatment With Single-Agent Carfilzomib

In the trial PX-171-010, researchers evaluated the effect of treating relapsed/refractory patients with single-agent carfilzomib for extended periods of time. The trial was an extension study of four Phase 1 and 2 clinical trials that examined the activity of single agent carfilzomib.

In order to be eligible for the extension study, patients must have completed the maximum 12 cycles of treatment in the first clinical trial.

The 59 participating patients continued to receive the same dose as in the previous trials (20 mg/m2 of carfilzomib on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle; in some trials, the carfilzomib dose was escalated to 27 mg/m2). Additionally, one patient continued to receive 4 mg of dexamethasone daily.

Researchers found that 24 patients (60 percent) are still being treated with carfilzomib with no apparent cumulative side effects. So far, 12 patients have completed over 18 months of carfilzomib treatment. The longest treatment period was 27 months. Sixteen patients discontinued treatment because of disease progression.

Based on these results, researchers concluded that patients could be treated with carfilzomib for extended periods of time without treatment-related side effects.

Safety Analysis of Single-Agent Carfilzomib

In a fourth analysis, researchers evaluated the safety of single-agent carfilzomib in relapsed/refractory myeloma from the results of three Phase 2 clinical trials.

Researchers found that carfilzomib was well tolerated in all four analyzed trials. They pointed out in particular that the low levels of neuropathy associated with carfilzomib make it a promising treatment for patients with pre-existing neuropathy.

The patients were treated with 20 mg/m2 of carfilzomib on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle for a maximum of 12 cycles. In three studies, the dosage of carfilzomib was increased to 27 mg/m2 after the first cycle in well-tolerated cases. In one study, patients also received low-dose dexamethasone.

The most common treatment-related side effects were fatigue, low red blood cell counts, nausea, shortness of breath, and low platelet counts. Only 4 percent of patients experienced peripheral neuropathy.

Researchers observed several serious side effects that are most likely treatment-related: pneumonia (3.5 percent), congestive heart failure (2.5 percent), acute kidney failure (1.7 percent), fever (1.2 percent), and shortness of breath (1 percent).

For more information about the four above studies, please refer to abstract 1938 (PX-171-004), abstract 1942 (PX-171-003-A1), abstract 1953 (PX-171-010), and abstract 1954 (Safety Analysis) on the ASH annual meeting website.

Photo by IndyDina with Mr. Wonderful on Flickr - some rights reserved.
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