Complete Response Rate Doubles When Aplastic Anemia Patients Receive Eltrombopag

By Gene Emery

January 06, 2022

(Reuters Health) - Adding the Novartis drug eltrombopag to standard immunosuppressive therapy with horse antithymocyte globulin (ATG) more than doubles the three-month complete response rate for people receiving first-time treatment for severe aplastic anemia, according to a new open-label phase 3 study.

The rate was 22% with eltrombopag and 10% without (P=0.01).

The difference persisted to the six-month mark, with rates of 68% in the 96-member experimental group versus 41% among the 101 control patients suffering from the rare but potentially-deadly disease where the bone marrow does not produce enough new blood cells.

However, the two-year survival rates in the two groups were similar.

"What's really important is that patients who receive the experimental treatment will respond quicker and better, and won't be transfused anymore. The patient is not coming to the hospital anymore. That's the main goal," chief author Dr. Regis Peffault de Latour of Saint Louis Hospital and the University of Paris told Reuters Health in a telephone interview. "There may be better overall survival, but that will come far later."

And the improvement came "without additional toxic effects," he and his team conclude in Thursday's New England Journal of Medicine.

The study, known as RACE, was done at 24 centers in six European countries. All the volunteers received cyclosporine in addition to horse ATG as standard treatment. None were eligible 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, a patient needed to achieve a hemoglobin level greater than 10 grams per deciliter, an absolute neutrophil count greater than 1,000 per cubic millimeter, and a platelet count greater than 100,000 per cubic millimeter.

By the 3-month mark, 22% in the eltrombopag group and 10% in the control group met that standard.

The overall response rates were 59% and 31% respectively.

At 12 months, 52% of the eltrombopag group had experienced a complete response versus 33% with standard treatment.

It typically only took 3 months for eltrombopag patients to see a response compared with 8.8 months with conventional therapy.

Patients who responded to the treatment became platelet-transfusion independent after 40 days. It was 68 days in the control group. Red-cell transfusion independence showed a similar pattern.

"In our trial, less severe aplastic anemia (severe vs. very severe) and younger age (<40 years) were associated with a better response," the researchers wrote. "Thus, both factors remain the two main clinical predictors, even in triple therapy for aplastic anemia."

Ten patients needed to have their eltrombopag discontinued before 6 months. In four patients, it was due to elevated liver enzyme levels. In two, it was due to a slight increase in reticulin deposition.

The two-year survival rate was 90% with eltrombopag and 85% without, which gave overlapping confidence intervals.

The team said that was expected "considering the additional effect of rescue treatment."

Eight people in the experimental group died during the trial compared with 14 in the control group.

A comparable number -- 11 and 12 respectively, underwent hematopoietic stem-cell transplantation and the rates of relapse at 18 months were not significantly different in the two groups.

Eltrombopag therapy is expected to save money because patients need fewer transfusions and spend fewer days in the hospital, Dr. de Latour said.

A follow-up study that tracks the patients for 10 to 15 years is underway.

Dr. de Latour said doctors are already embracing the treatment.

"For more than 30 years we were not able to improve the standard treatment of patients with aplastic anemia," he said. "This is becoming the first line for those patients. The median time for response is about 3 months and in the standard arm it's about 9 months. You can see it's a better response and you're spending less time in the hospital. So of course patients are also very happy with it."

Ironically, while the treatment has been benefiting patients in over 30 countries -- including the United States -- in the wake of a 2017 phase 2 trial that showed a significant benefit, it was never approved by the European Medicines Agency, Dr. de Latour said.

The Europeans were waiting for confirmation, he explained. "Now we have this trial that has really proven eltrombopag works and it's becoming the standard of care worldwide, but it's not approved in Europe. I hope the EMA will change its mind."

SOURCE: The New England Journal of Medicine, online January 5, 2022.