CC-486을 이용한 유지요법은 급성골수성 백혈병 환자의 생존을 연장한다.

2020년 1월 16일 : 국립암연구소 제공

※유지 요법: 최대의 치료 효과를 얻을 수 있는 양의 약물을 투여한 후, 같은 효과를 유지시키기 위해 소량씩의 투여를 계속하는 요법. 금단 증상을 완화시키거나 해독 효과를 높일 수 있다. 마약 중독자의 치료 등에 쓰인다.

한 대형 임상 실험 결과에 따르면, 시험용 약물은 급성 골수성 백혈병(AML) 성인의 생존을 연장시켰다. 정제로 만들어진 CC-486은 또 다른 치료제인 아자시티딘(상표명 : 비다자)과 관계가 있다.

CC-486은 집에서 복용할 수 있는 알약인 반면, 아자시티딘은 피하 주사나 정맥을 통한 주입으로 투여해야 하므로 병원이나 진료실에서 투여된다. 아자시티딘은 혈액암 환자를 단독으로 치료하거나 다른 약물과 결합하여 치료하는 데 사용된다.

새로운 연구에서 CC-486은 공격적인 화학요법을 받은 후 회복 중인 급성 골수성 백혈병 성인 환자를 위한 유지요법으로 테스트되었다.

급성 골수성 백혈병의 성인 환자의 많은 수는 초기 치료 후에 관해가 된다. 그러나 대부분의 경우 암은 초기 치료 후 추가 또는 통합 화학 치료를 받더라도 일반적으로 재발한다. 초기 치료 후에 재발되는 급성 골수성 백혈병(AML)은 치료하기가 더 어렵고 대부분의 환자들은 몇 달 안에 죽는다.

호주 멜버른에 있는 알프레드 병원의 앤드류 웨이 박사 실험의 주임 원구원에 따르면, CC-486은 초기 치료 후 환자가 관해 상태를 유지하는 기간과 전체 생존을 연장하는 최초의 유지요법이다. 그는 12월 10일 플로리다 주 올랜도에서 개최된 미국 혈액학 협회 연례 회의에서 이 실험의 결과를 발표했다.

"이 획기적인 임상 실험의 긍정적인 결과에 기초하여, CC-486을 사용한 유지요법이 잠재적인 새로운 치료 기준을 보여주기를 희망한다,"고 웨이 박사는 연구 결과에 대한 언론 브리핑에서 말했다.

연구에 참여하지 않은 펜실베이니아 대학 병원의 혈액 암 전문의 셀리나 루거 박사는 "전체 생존의 증가는 중요하고 흥미롭다"고 말했다. 이어 "상대적으로 견디기 쉬운 약물로 급성 골수성 백혈병의 유지요법의 역할을 보여주고 있다"고 덧붙였다.

그러나 루거 박사는 이 약을 가장 잘 사용하는 방법과 부작용 관리 방법, 그리고 치료 중인 환자에게 얼마나 오랫동안 투여해야 하는지에 대한 더 많은 정보가 필요하다고 경고했다. 그리고 "우리는 어떤 환자들이 가장 많은 혜택을 받을 수 있는가를 배울 필요가 있다고 생각한다.“고 루거 박사가 말했다.

Maintenance Therapy with CC-486 Extends Survival of Adults with AML

January 16, 2020, by NCI Staff

An investigational drug extended survival of adults with the blood cancer acute myeloid leukemia (AML), according to results from a large clinical trial. The drug, CC-486, is related to another therapy called azacitidine (Vidaza).

CC-486 is a pill that can be taken at home, whereas azacitidine is given as an injection under the skin or as an infusion through a vein and is administered at a hospital or doctor’s office. Azacitidine is used to treat patients with some types of blood cancer, either alone or in combination with other drugs.

In the new study, CC-486 was tested as a maintenance therapy for adults with AML that was in remission (meaning there were no signs of cancer) after receiving aggressive chemotherapy.

Many adults with AML go into remission after initial therapy. But for most, the cancer typically returns—even if they get additional, or consolidation, chemotherapy after initial therapy. AML that comes back after initial therapy is more difficult to treat and most patients die within a few months.

CC-486 is the first maintenance therapy to extend how long patients remain in remission following initial treatmentExit Disclaimer and how long they live, according to the trial’s lead investigator, Andrew Wei, Ph.D., of the Alfred Hospital, in Melbourne, Australia. He presented the trial’s findings at the American Society of Hematology annual meeting in Orlando, Florida, on December 10.

“Based on the positive results of this landmark clinical trial, we hope that maintenance therapy with CC-486 might represent a potential new therapeutic standard,” Dr. Wei said during a press briefing on the study’s findings.

The increase in overall survival “is important and exciting,” said Selina Luger, M.D., a blood cancer specialist at the Hospital of the University of Pennsylvania, who was not involved in the study. “It shows a role for maintenance therapy for AML with a drug that was relatively easy to tolerate,” she added.

However, Dr. Luger cautioned that more information is needed about how best to use the drug, how to manage its side effects, and how long it should be given to patients in remission. And, she continued, “I think we need to learn which patients are most likely to benefit.”

Searching for an Effective Maintenance Therapy

Even though many people with AML go into remission after initial treatment, some cancer cells are thought to remain—cells that can eventually multiply and cause a relapse. The goal of maintenance therapy is to eliminate those remaining cells.

Because maintenance therapy is effective for other kinds of blood cancer, such as acute lymphoblastic leukemia (ALL), scientists have long been searching for an effective maintenance therapy for AML.

Although several studies have identified maintenance therapies that delay AML from returning, none has shown an improvement in overall survival—until now.

Nearly 500 people with AML who were aged 55 or older enrolled in the international trial known as QUAZAR AML-001. The trial was funded by Celgene, the manufacturer of CC-486.

All participants were enrolled within 4 months of going into remission after initial chemotherapy treatment. The majority (80%) of participants also received some form of consolidation chemotherapy. All patients were considered to be at intermediate or high risk for relapse based on certain genetic characteristics of their leukemia cells.

At the time of enrollment, all participants were unable to have a stem cell transplant. This is the standard treatment recommended for patients at high risk of relapse, but some patients may not be well enough to undergo the difficult procedure or may be unable find a donor, Dr. Luger explained.

Participants were randomly assigned to receive either CC-486 or a placebo. Treatment was given until a patient relapsed or experienced unacceptable side effects. Patients could also stop treatment if they became eligible for a stem cell transplant. Since the study was only open to patients not planning to get a transplant, that would likely only happen if a patient suddenly matched with a transplant donor, Dr. Luger said.

An Improvement in Overall Survival

Median overall survival, the study’s primary endpoint, was 10 months longer for those in the CC-486 group than in the placebo group (25 months versus 15 months).

CC-486 also extended how long patients lived without their cancer coming back (relapse-free survival) by about 5 months (10 months versus 5 months). More than 40 patients currently remain on the investigational treatment.

A “striking finding,” said Dr. Wei, was that these benefits were observed regardless of patients’ risk of relapse, the number of cycles of consolidation chemotherapy they received, or whether they were in complete remission or a form of remission called complete remission with incomplete count recovery (CRi). People with CRi have lower-than-normal levels of some blood cells and typically have poorer outcomes than those in complete remission.

But, said Dr. Luger, physicians want to know if there is a specific group of patients with AML who are more likely to benefit from this treatment. That information will likely become available as more study data are generated, she explained.

The most common side effects of CC-486 were nausea, vomiting, and diarrhea. For some patients, those effects could be limited with other medicines, Dr. Wei noted.

More patients in the CC-486 group experienced serious side effects, including a lower-than-normal number of white blood cells (neutropenia) and infections. Very few patients discontinued treatment due to side effects, the investigators noted, but most of those who did had experienced gastrointestinal effects. There were no treatment-related deaths.

In addition, changes in self-reported quality of life were similar between patients in the two groups.

Testing CC-486 In Place of Azacitidine

Although CC-486 and azacitidine are derived from the same chemical, they are not equivalent treatments, Dr. Luger stressed. Each drug may affect leukemia cells differently, she said.

There are differences in how each drug is processed by the body (what’s known as pharmacokinetics), such as how it is absorbed, distributed, and eliminated.

That may explain, in part, why a small study of azacitidine as maintenance therapy for adults with AML did not show an improvement in overall survival, Dr. Wei said. Another possible explanation, he added, is that the duration of treatment was shorter for azacitidine than for CC-486. That could be because azacitidine infusions are less convenient for patients, he explained.

Dr. Luger noted that azacitidine is used to treat adults with AML who are unable to receive the standard initial chemotherapy, and these patients often receive the treatment for an extended period of time, until they relapse.

“I think another question we can ask is, for those who achieve remission with intravenous azacitidine, will they be able to transition to the oral drug instead of staying on the intravenous drug indefinitely?” she said.

In addition, several ongoing studies are testing azacitidine in combination with targeted therapies, Dr. Wei said, and CC-486 could also be tested in combination with targeted drugs.

Given the results of this current trial, he continued, CC-486 might represent a “fundamental building block for new combinations that will hopefully have transformative potential for patients with this disease.”