Bristol-Myers Squibb (BMS) recently announced that the U.S. Food and Drug Administration (FDA) has approved Pomalyst (pomalidomide), which is an immunomodulator with anti-tumor activity for the treatment of Kaposi sarcoma (Kaposi sarcoma) , KS) patients, specifically: (1) AIDS-related Kaposi sarcoma patients whose disease has developed resistance to highly effective antiretroviral drugs (HAART); (2) HIV-negative Kaposi sarcoma patients
It is worth mentioning that Pomalyst is the only oral and first new therapeutic drug approved for the treatment of Kaposi's sarcoma (KS) for more than 20 years. It should be pointed out that patients with AIDS-related Kaposi's sarcoma should continue to use HAART to treat HIV according to the doctor's recommendations.
Pomalyst received the FDA's accelerated approval, breakthrough drug qualification (BTD), orphan drug qualification (ODD) for the treatment of the above Kaposi's sarcoma indication. This accelerated approval is based on the total response rate (ORR) data from the Phase I / II open-label, single-arm clinical trial (12-C-0047). Continued approval for these indications will depend on the verification and description of clinical benefits in confirmatory trials.
Kaposi's sarcoma is a rare cancer, usually manifested as skin lesions, but can also develop into several other parts of the body, including the lungs, lymph nodes, and digestive system. In the United States, the annual incidence of this disease is 6 parts per million, and it mainly affects people with low immune function. Pomalyst is an oral drug and is the first new treatment approved for the treatment of patients with Kaposi's sarcoma in more than 20 years.
Diane McDowell, vice president of global medical affairs at Bristol-Myers Squibb, said: "Patients with Kaposi's sarcoma have little control over their disease in the past 20 years. We are pleased that further research on Pomalyst in this rare disease area has enabled us Ability to provide patients with much-needed oral treatment options. "
Robert Yarchan, MD, director of the Division of HIV and AIDS Malignancies at the Cancer Research Center (CCR) of the National Cancer Institute (NCI), said: "Pomalyst showed positive results in patients with Kaposi's sarcoma, regardless of their HIV status. In addition, the drug also provides an oral therapy with a mechanism of action different from the cytotoxic chemotherapy drugs commonly used to treat Kaposi's sarcoma. "
As stated in the black box warning of the prescription information, Pomalyst may cause harm to the fetus and is prohibited for pregnant women. Pomalyst is only available through Pomalyst REMS®, a restricted distribution plan. In patients receiving Pomalyst, deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke may occur, and thromboprophylaxis should be given.
This approval is based on data from an open-label, single-arm phase I / II study 12-C-0047. The study assessed the safety, pharmacokinetics, and efficacy of Pomalyst in HIV-positive and HIV-negative symptomatic Kaposi's sarcoma patients, most of whom have advanced disease.
The trial was conducted by a team led by Robert Yarchoan under the Collaborative Research and Development Agreement (CRADA). A total of 28 patients (18 HIV-positive and 10 negative) received Pomalyst at a dose of 5 mg and took it orally once a day for 21 cycles (a cycle of 28 days) until disease progression or unacceptable toxicity. The trial excluded patients with symptomatic lung or visceral Kaposi's sarcoma, a history of venous or arterial thromboembolism, and procoagulant diseases. During the entire course of treatment, the patient received aspirin 81mg thromboprophylaxis once a day. The median time from initiation of treatment to the occurrence of the first remission was 1.8 months (0.9-7.6).
The primary endpoint of the study was the overall response rate (ORR, including complete response [CR], clinical complete response [cCR], partial response [PR]), which was investigated by the investigator according to the Cancer Committee of the AIDS Clinical Trials Group (ACTG) against Kaposi The sarcoma response criteria were evaluated.
The data showed that among all patients, ORR was 71% (20/28; 95% CI: 51,87), of which 24% (4/28) patients achieved CR and 57% (16/28) patients achieved PR . The median duration of remission (DOR) for all patients was 12.1 months (95% CI: 7.6, 16.8). In addition, among patients with remission, 50% of patients maintained remission during 12 months of Pomalyst treatment.
The most common adverse reactions (≥30%) including laboratory abnormalities are decreased absolute neutrophil or white blood cell count, increased creatinine or glucose, rash, constipation, fatigue, hemoglobin, platelets, phosphate, albumin or calcium Reduced, increased ALT, nausea and diarrhea. 11% (3/28) of patients were permanently discontinued due to adverse reactions. No new safety signals were found. In Kaposi's sarcoma, the safety of Pomalyst is consistent with the safety of known Pomalyst in approved indications.
Kaposi sarcoma (Kaposi sarcoma, KS) is a rare cancer, usually manifested as skin lesions, but can also develop to several other parts of the body, including the lungs, lymph nodes, and digestive system. Kaposi's sarcoma is caused by Kaposi's sarcoma-associated herpes virus (KSHV, also known as human herpes virus type 8 [HHV-8]), and is most commonly seen in HIV-infected people with compromised immune function.
Although the combined use of antiretroviral therapy (cART or HAART) has reduced the incidence of Kaposi's sarcoma in the United States, the disease still occurs at a rate of about 6 cases per million people. Kaposi's sarcoma is more common in areas with less AIDS treatment in the world. In sub-Saharan Africa and other regions, more people are infected with Kaposi's sarcoma-associated herpes virus (KSHV), which is the most common among men in some countries Tumor.
Pomalyst is an immunomodulator with anti-tumor activity. The drug is a thalidomide analog that has been approved for the treatment of adult patients: (1) combined with dexamethasone for the treatment of multiple myeloma (MM), Specifically, patients who have previously received at least 2 therapies (including lenalidomide and proteasome inhibitors), showed disease progression during the last therapy, or within 60 days after completion of treatment; (2) Kaposi's sarcoma ( KS) patients, specifically AIDS-related KS patients and HIV-negative KS patients who failed HAART treatment.