Σάββατο, 13 Μαΐου 2017

PEMBROLIZUMAB APPROVED BY EMA FOR HODGKIN LYMPHOMA

Immunotherapy with pembrolizumab (Keytruda, Merck & Co) has been approved for use in certain patients with Hodgkin's lymphoma, making it the second programed cell death (PD) inhibitor for use in this hematologic malignancy.
Specifically, pembrolizumab is approved for use in adult patients with relapsed or refractory classic Hodgkin's lymphoma in whom autologous stem cell transplant (ASCT) and treatment with brentuximab vedotin (Adcetris, Seattle Genetics) have failed or who are transplant-ineligible and in whom brentuximab therapy has failed.
The approval allows marketing of  the drug in all 28 European Union member states plus Iceland, Lichtenstein, and Norway, at the approved dose of 200 mg every 3 weeks until disease progression or unacceptable toxicity.
Pembrolizumab is already approved for Hodgkin's lymphoma in the United States.
Another PD inhibitor, nivolumab (Opdivo, Bristol-Myers Squibb), is also approved for use in Hodgkin's lymphoma in both Europe and  the United States. These approvals cover use of nivolumab in patients with Hodgkin's lymphoma who have relapsed or progressed after undergoing ASCT and are receiving post-transplantation treatment with brentuximab vedotin. 

Clinical Data 

The new approval was based on data in 241 patients from two company-sponsored open-label studies, KEYNOTE-087 and KEYNOTE-013. Details of the data from the trials were summarized in a company press release.  
KEYNOTE-087 was conducted in 210 patients, of whom 81% were refractory to at least one prior therapy, including 35% who were refractory to first-line therapy. Additionally, 61% of patients had undergone prior ASCT, 38% were transplant ineligible, 17% had not previously received brentuximab vedotin, and 36% had prior radiation therapy.
Patients received pembrolizumab, 200 mg every 3 weeks, until unacceptable toxicity or documented disease progression.
Efficacy analysis showed an overall response rate (ORR) of 69% with a complete remission rate (CRR) of 22% and a partial remission rate (PRR) of 47%. The median follow-up time was 10.1 months.
Among the 145 responding patients, the median duration of response was 11.1 months, with 76% of responding patients having responses of 6 months or longer.
The KEYNOTE-013 trial involved 31 patients who received pembrolizumab, 10 mg/kg every 2 weeks, until unacceptable toxicity or documented disease progression. Again, most patients (87%) were refractory to at least one prior therapy, including 39% who were refractory to first-line therapy. In addition, 74% patients had undergone prior ASCT, 26% were transplant ineligible, and 42% had prior radiation therapy.
The efficacy analysis showed an ORR of 58%, with a CRR of 19% and a PRR of 39%. The median follow-up time was 28.7 months. Among the 18 responding patients, the median duration of response was not reached (range, 0.0+ to 26.1+ months); 80% of patients had a response of 6 months or longer and 70% had a response of 12 months or longer.
The safety analysis supporting the European approval was based on 3194 patients with advanced melanoma, non-small cell lung cancer, or classic Hodgkin's lymphoma across four doses (2 mg/kg every 3 weeks, 200 mg every 3 weeks, or 10 mg/kg every 2 or 3 weeks) in clinical studies, the company notes. The most common adverse reactions (>10%) with pembrolizumab were fatigue (22%), pruritus (15%), rash (13%), diarrhea (12%), and nausea (10%). Most adverse reactions reported were of grade 1 or 2 severity. The most serious adverse reactions were immune-related adverse reactions and severe infusion-related reactions.

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