Photo from Business Wire
The European Commission (EC) has approved nivolumab (Opdivo) for the treatment of adults with relapsed or refractory classical Hodgkin lymphoma (cHL) who have already received an autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV).
Nivolumab is the first PD-1 inhibitor approved in the European Economic Area as a treatment for a hematologic malignancy.
The EC previously approved nivolumab to treat advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. In Europe, nivolumab is marketed by Bristol-Myers Squibb.
Trials in cHL
The EC’s approval of nivolumab in cHL is based on an integrated analysis of data from 2 trials—the phase 1 CheckMate -039 trial and the phase 2 CheckMate -205 trial.
In CheckMate -039, researchers evaluated nivolumab in patients with cHL, non-Hodgkin lymphoma, and multiple myeloma. Results from this trial were presented at the 13th International Congress on Malignant Lymphoma in June 2015.
In CheckMate -205, researchers are evaluating nivolumab in 4 cohorts of cHL patients. Cohort A includes patients who previously received auto-HSCT and were BV-naïve at enrollment (n=63). Cohort B includes patients who previously received auto-HSCT followed by BV (n=80).
Cohort C includes patients who previously received BV before and/or after auto-HSCT (n=100). And cohort D, which is currently enrolling, is an evaluation of nivolumab in combination with chemotherapy in newly diagnosed, advanced-stage cHL patients who are treatment-naïve (n=50).
Results from cohort B were presented at the 21st Congress of the European Hematology Association in June 2016. Results from cohort C were presented at the 10th International Symposium on Hodgkin Lymphoma last month.
Integrated analysis
The analysis included cHL patients from CheckMate -205 and -039 who had received auto-HSCT and BV.
In the efficacy population (n=95), the objective response rate was 66%. The percentage of patients with a complete response was 6%. Twenty-three percent of patients had stable disease.
The median time to response was 2.0 months (range, 0.7-11.1), and the median duration of response was 13.1 months (range, 0.0+, 23.1+). At 12 months, the progression-free survival rate was 57%.
The safety of nivolumab in cHL was evaluated in 263 patients from CheckMate -205 (n=240) and CheckMate -039 (n=23). Serious adverse events (AEs) occurred in 21% of these patients.
The most common serious AEs (reported in at least 1% of patients) were infusion-related reactions, pneumonia, pleural effusion, pyrexia, rash, and pneumonitis.
The most common AEs (reported in at least 20% of patients) were fatigue (32%), upper respiratory tract infection (28%), pyrexia (24%), diarrhea (23%), and cough (22%).
Twenty-three percent of patients had a dose delay resulting from an AE, and 4.2% of patients discontinued treatment due to AEs.
Forty patients went on to allogeneic HSCT after nivolumab, and 6 of these patients died from complications of the transplant. The 40 patients had a median follow-up from allogeneic HSCT of 2.9 months (range, 0-22).
Because of these deaths, the US Food and Drug Administration asked Bristol-Myers Squibb to study the safety of allogeneic HSCT after nivolumab.
