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Kyprolis-Revlimid-Dexamethasone Combo Shows Encouraging Results In Older Newly Diagnosed Myeloma Patients (IMW 2013)

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Published: Apr 17, 2013 2:55 pm

A subgroup analysis of recent Phase 1/2 clinical trial results shows that Kyprolis in combination with Revlimid and low-dose dexamethasone is effective and well tolerated in newly diagnosed multiple myeloma patients over the age of 65.

All of the evaluated patients responded to treatment, with 83 percent of patients reaching at least a near complete response.

According to Dr. Andrzei Jakubowiak of the University of Chicago Medical Center, who presented the findings earlier this month at the International Myeloma Workshop (IMW) in Kyoto, Japan, the response rates compare favorably to the best response rates of other induction therapies in this patient population.

He concluded that these findings warrant a Phase 3 study of the combination regimen in myeloma patients of all age groups.

Background

Kyprolis (carfilzomib) was approved by the U.S. Food and Drug Administration last year for the treatment of multiple myeloma patients who have received at least two prior therapies, including Velcade (bortezomib) and an immunomodulatory agent – such as Revlimid (lenalidomide), thalidomide (Thalomid), or Poma­lyst (pomalidomide) – and who progressed within 60 days of completing their most recent regimen (see related Beacon news).

Kyprolis is a proteasome inhibitor in the same class of drugs as Velcade.

While many clinical trials target younger patients, the majority of multiple myeloma patients are over 65 years of age, and a third are over 75 years.

The National Comprehensive Cancer Network (NCCN) currently recommends older myeloma patients be treated with Revlimid or Velcade plus dexamethasone (Decadron), or melphalan (Alkeran) and prednisone plus Velcade, Revlimid, or thalidomide.  Most of these regimens have overall response rates of 60 percent to 80 percent in older myeloma patients.

Recent studies have demonstrated that Kyprolis combination therapies, such as Kyprolis, cyclo­phos­phamide (Cytoxan), and dexamethasone, or Kyprolis, melphalan, and prednisone, are highly active in older myeloma patients, leading to response rates of approximately 90 percent.

Results from all patients who participated in the Phase 1/2 study of Kyprolis plus Revlimid and low-dose dexamethasone in newly diagnosed patients showed that the combination is highly active in myeloma patients of all ages. Overall, 98 percent of patients responded to the treatment, and at two years, 92 percent of patients had not progressed (see related Beacon news).

Based largely on the results of this trial, the NCCN recently added the Kyprolis-Revlimid-dexamethasone regimen to its guidelines as an alternative treatment option for newly diagnosed myeloma patients who are eligible for stem cell transplantation (see related Beacon news).

Study Design

Given the promising results for the Kyprolis-Revlimid-dexamethasone combination across all ages, the trial investigators decided to further analyze the results to determine the safety and efficacy of the combination in older myeloma patients.

For this subgroup analysis, the researchers assessed treatment outcomes for the subset of 23 patients who were at least 65 years of age. The median patient age for this subgroup was 72 years.

Over the course of a 28-day treatment cycle, patients received 20 mg/m2, 27 mg/m2, or 36 mg/m2 of Kyprolis on days 1, 2, 8, 9, 15, and 16; 25 mg of Revlimid on days 1 to 21; 40 mg of dexamethasone weekly during cycles 1 to 4; and 20 mg of dexamethasone weekly during cycles 5 to 8.

For cycles 8 to 24, patients continued on the regimen, but received Kyprolis only on days 1, 2, 15, and 16. After cycle 24, patients could continue to receive 25 mg of Revlimid on days 1 to 21.

After the fourth cycle, transplant-eligible patients had the option of receiving a stem cell transplant.

Study Results

After a median of 12 treatment cycles, all of the older patients evaluated reached at least a partial response. Specifically, 61 percent reached a stringent complete response, 22 percent reached a near complete response, 4 percent reached a very good partial response, and 13 percent achieved a partial response. The share of patients who achieved a stringent complete response was higher among the older patients, compared to patients of all ages (61 percent versus 42 percent, respectively).

Response rates improved with longer duration of treatment. Of the 17 older patients who completed at least 8 cycles of treatment, all of them reached a near complete response and 76 percent reached a stringent complete response.

After a median follow-up of 13 months, all older patients were progression-free and alive. In comparison, 7 percent of younger patients progressed during that time.  The one-year and two-year progression-free survival rates were 97 percent and 92 percent, respectively, for patients of all ages.

According to Dr. Jakubowiak, side effects tended to be more common in older patients.  In addition, dose modifications and discontinuations due to side effects were more common in older patients.

Common severe to life-threatening side effects in the older group included high blood sugar levels, low platelet counts, low red blood cell counts, low white blood cell counts, and low phosphate levels during the first eight treatment cycles. Peripheral neuropathy was experienced by 13 percent of the older patients, but all cases were mild to moderate in nature

For more information, please see Dr. Jakubowiak’s presentation slides, which he has made available for download and viewing as a courtesy to The Beacon’s readers.

Photo by pedrosimoes7 on Flickr -- some rights reserved.
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One Comment »

  • LeeSa said:

    My mom has been taking Kyprolis since January. Now for the past few weeks this being her 4th cycle, her legs are extremely swollen. The doctors are aware, but I am very concerned because she tries her best to move around the house.. Her treatments are on Thursdays and Fridays and it’s very hard for her to go up and down the stairs. What can be done or what can I ask the doctors to do. I am just afraid about the whole situation and I don’t want them to stop her Treatments.