(Reuters Health) The addition of the Novartis drug eltrombopag to standard immunosuppressive therapy using antithymocyte globulin from horses (ATG) more than doubles the three-month complete response rate for patients who are receiving treatment for the first time for severe anemia, according to a brand-new open-label phase 3 study.
The rate was 22% for eltrombopag and 10% with (P=0.01).
The six-month mark was characterized by a 68% rate in the 96-member group, as compared to 41% in the 101 patients with the rare, but possibly fatal disease. This is where the bone marrow fails to produce enough blood cells.
However the survival rates over the two years in both groups were very comparable.
“What is most important is that patients given the experimental treatment will respond quicker and better, and will not need to be transfused once again. The patient is not coming to the hospital anymore. “That’s the primary goal,” Dr. Regis Peffault de Latour, chief author at Saint Louis Hospital and University of Paris said to Reuters Health via telephone interview. “There could be a higher overall survival, but it will be later.”
And the improvement came “without additional toxic effects,” he and his team conclude in the Thursday issue of New England Journal of Medicine.
RACE was a study which took place in 24 centers across six European countries. All the volunteers received cyclosporine as well as horse ATG as a standard treatment. None of the volunteers were suitable for hematopoietic stem cell transplantation.
Novartis, which sells eltrombopag under the brand names Promacta and Revolade, and Pfizer paid for the study.
For a complete response, patients must have an hemoglobin level of more than 10 grams per deciliter, an absolute neutrophil count higher than 1,000 per cubic millimeter and a platelet count of more than 100,000 per cubic millimeter.
At the 3 month mark, 22% of the eltrombopag and 10% of the control groups met this threshold.
The response rates for all respondents were 59 percent and 31% respectively.
52% of the eltrombopag patients had seen an effective response after 12 months, compared with 33% who received the standard treatment.
Patients who received eltrombopag therapy experienced a response in 3 months, in comparison to 8.8 months with traditional treatment.
Patients who responded to the treatment were able to stop platelet transfusion after 40 days. It took 68 days for the control group. Red-cell transfusion independance revealed a similar pattern.
“In our trial we found that less severe aplastic aplastic aemia (severe vs. extremely severe) and younger age (<40 years) were associated with better response," the researchers wrote. "Thus both factors are the two major clinical predictors, even in triple therapy for aplastic aplastic aemia."
Ten patients required their eltrombopag removed prior to 6 months. In four cases it was due to elevated levels of liver enzymes. In two, it was due to a slight increase in the deposition of reticulin.
The two-year survival rate was 90% for eltrombopag and 85% without, which gave the same confidence intervals.
“Considering the additional effect of the rescue treatment,” the team stated that they had anticipated this.
Eight people died in the experimental group, as compared to 14 in the control group.
Similar numbers 11, and 12 underwent hematopoietic stem cell transplantation. Relapse rates at 18 months were not significantly different between the two groups.
Dr. de Latour stated that Eltrombopag therapy can be an option to save money since patients require less transfusions and spend less time in hospitals.
A follow-up study is in process that will monitor patients for 10 to 15 year.
Dr. de Latour stated that doctors already embrace the treatment.
He stated that “for more than 30 years, we have not able improve the standard treatment for patients with Aplasticanemia.” “This is now the first line treatment for those patients. The standard arm has a median response time of 3 months, while the standard arm takes 9 months. You can see it’s more effective and you’re spending less time in the hospital. Of course, patients are also very happy with the results.”
It is ironic that the treatment, which was beneficial to patients across 30 countries, including the United States, in the aftermath of a phase 2 study which showed a significant improvement however, was not approved by the European Medicines Agency, Dr. de Latour stated.
The Europeans were waiting for confirmation, he said. “Now we have this trial that has really demonstrated that eltrombopag is effective and is becoming the standard of care worldwide however it’s not yet approved in Europe. I hope that the EMA will reconsider its position.
SOURCE: https://bit.ly/3qy1XpI The New England Journal of Medicine, online January 5, 2022.
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