Carfilzomib-Revlimid-Dexamethasone Combination Is Well Tolerated As Longer-Term Multiple Myeloma Treatment (ASCO 2010)

Preliminary results from an ongoing Phase 1b clinical trial suggest that carfilzomib (Kyprolis) in combination with Revlimid (lenalidomide) and low-dose dexamethasone (Decadron) is well-tolerated over extended periods of therapy in patients who have relapsed or are resistant (refractory) to previous myeloma treatment.
The findings were presented Friday at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
Carfilzomib is a new therapy being developed by Onyx Pharmaceuticals and studied for the treatment of patients with relapsed or refractory myeloma. It works similarly to Velcade (bortezomib) by preventing the breakdown of protein in cancer cells, triggering their death. In clinical trials currently underway with the drug, treatment with carfilzomib results in less damage to the peripheral nervous system and fewer cases of low white blood cells than other currently approved multiple myeloma therapies.
The goal of this Phase 1b study was to determine the safety and maximum recommended dose of carfilzomib administered with Revlimid and low-dose dexamethasone, a regimen abbreviated CRd, in patients with relapsed or refractory myeloma. The researchers also studied the efficacy of CRd in these patients.
Results published in the ASCO abstract report on safety and efficacy results for 40 patients. The results presented today at the meeting include an additional 44 patients enrolled in the expansion phase of the trial, further testing full-dose CRd.
All patients enrolled in this clinical trial were previously treated, most with Velcade, Revlimid, or thalidomide (Thalomid). Among the initial 40 participants, 47 percent were refractory to their last therapy, and 84 percent had a history of nerve damage to the limbs related to previous treatments. Patients were given different doses of the CRd combination therapy in a 28-day cycle.
Researchers found that at the full dose of CRd, 6 percent of patients showed a complete response, 27 percent showed a very good partial response, and 42 percent showed a partial response for an overall response rate of 75 percent. They also found that this response improved with long-term therapy (up to 18 cycles of treatment).
More than a third of the patients have received CRd for more than a year and are still participating in the study. All of these patients, however, received reduced doses of carfilzomib and Revlimid.
Researchers did not observe any dose-limiting side effects over an extended period of treatment (14 to 23 months). None of the patients showed signs of severe nerve damage, blood clotting, or fatigue. Although some patients experienced seriously low levels of white blood cells (23 percent of patients), platelets (18 percent), and red blood cells (12 percent), researchers found that levels returned to normal after treatment.
Based on the results of this Phase 1b study, researchers concluded that full-dose CRd was well-tolerated in relapsed/refractory myeloma patients, including patients heavily pretreated with Velcade, Revlimid, or thalidomide as well as patients with a history of treatment-related nerve damage. Additionally, CRd was well-tolerated throughout long-term treatment.
The researchers added that CRd is effective in patients previously treated with Velcade, Revlimid, or thalidomide.
A phase 3 trial comparing full-dose CRd with Rd will begin recruiting patients later this year.
For more information, please see abstract 829 on the ASCO meeting website.
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- Once-Weekly High-Dose Kyprolis Yields Deeper Responses And Longer Remissions Than Twice-Weekly Kyprolis (ASCO & EHA 2018)
- Eyelid-Related Complications Of Velcade Therapy: New Insights And Recommendations