Nivolumab gets US accelerated approval for Hodgkins lymphoma18 May 2016
The U. S. FDA granted accelerated approval to nivolumab for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin. The approval was based on two single-arm, multicenter trials of nivolumab in adults with relapsed or refractory cHL.
Nivolumab was granted Breakthrough Therapy Designation for the treatment of relapsed or refractory cHL after failure of autologous HSCT and brentuximab vedotin. Nivolumab also has Orphan Drug status for the treatment of Hodgkin lymphoma.
Clinical details and results
These most recent trials enrolled patients regardless of PD-L1 expression status on Reed-Sternberg cells. The primary efficacy endpoint was objective response rate (ORR) as determined by an independent radiographic review committee. Additional outcome measures included duration of response (DOR).
Efficacy was evaluated in 95 patients previously treated with autologous HSCT and post-transplantation brentuximab vedotin. Patients had a median of 5 prior systemic regimens and received a median of 17 doses of nivolumab.
- Single-agent nivolumab produced a 65% objective response rate with 58% partial remission and 7% complete remission.
- The median time-to-response was 2.1 months.
- The estimated median duration of response was 8.7 months.
What about the adverse reactions?
Safety was evaluated in 263 patients with relapsed or refractory cHL, of whom ninety-eight per cent of patients had received autologous HSCT. Patients received a median of 10 doses of nivolumab (range: 1, 48) at the approved dose-schedule. The most common (reported in at least 20%) adverse reactions of any grade were fatigue, upper respiratory tract infection, cough, pyrexia, and diarrhea.
Additional common adverse reactions (reported in at least 10%) included rash, pruritus, musculoskeletal pain, nausea, vomiting, abdominal pain, headache, peripheral neuropathy, arthralgia, dyspnea, infusion-related reactions, and hypothyroidism or thyroiditis.
Other immune-mediated adverse reactions, occurring in 1% to 5% of patients, included rash, pneumonitis, hepatitis, hyperthyroidism, and colitis. Serious adverse reactions were reported in 21% of patients, the most common of which, reported in 1% to 3% of patients, were pneumonia, pleural effusion, pneumonitis, pyrexia, infusion-related reaction, and rash.
The FDA has required further safety study
A new “Warning and Precaution” was issued for complications of allogeneic HSCT after nivolumab.
Transplant-related deaths have occurred, and health care professionals should follow patients closely for early evidence of transplant-related complications, such as hyper acute graft-versus-host disease (GVHD), severe acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease, and other immune-mediated adverse reactions.
The FDA has required the manufacturer to further study the safety of allogeneic HSCT after nivolumab. The recommended dose-schedule of nivolumab is 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity. Continued approval for the cHL indication may be contingent upon verification of clinical benefit through a randomized phase 3 trial.Source: eCancer News