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Pembrolizumab (Keytruda)
The European Commission (EC) has approved the anti-PD-1 therapy pembrolizumab (Keytruda) for use in patients with classical Hodgkin lymphoma (cHL).
The drug is now approved to treat adults with relapsed or refractory cHL who have failed autologous stem cell transplant (auto-SCT) and brentuximab vedotin (BV) or who are transplant-ineligible and have failed treatment with BV.
The approval allows marketing of pembrolizumab for this indication in the European Economic Area (EEA).
This is the first approval for pembrolizumab in a hematologic malignancy in the EEA. The drug was previously approved there as a treatment for melanoma and non-small-cell lung cancer.
The new approval for pembrolizumab was based on data from the KEYNOTE-087 and KEYNOTE-013 trials.
Results from KEYNOTE-013 were presented at the 2016 ASH Annual Meeting (abstract 1108), and results from KEYNOTE-087 were recently published in the Journal of Clinical Oncology.
KEYNOTE-087
In this phase 2 trial, researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:
- Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
- Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
- Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.
Across all 210 enrolled patients, the overall response rate (ORR) was 69.0%, and the complete response (CR) rate was 22.4%.
In Cohort 1 (n=69), the ORR was 73.9%, and the CR rate was 21.7%.
In Cohort 2 (n=81), the ORR was 64.2%, and the CR rate was 24.7%.
In Cohort 3 (n=60), the ORR was 70.0%, and the CR rate was 20%.
For the entire study cohort, the median duration of response was not reached, and the median overall survival (OS) was not reached. At 9 months, the OS was 97.5%, and the progression-free survival (PFS) was 63.4%.
The most common treatment-related adverse events (AEs) were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).
The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).
There were 9 discontinuations because of treatment-related AEs and no treatment-related deaths.
KEYNOTE-013
KEYNOTE-013 is a phase 1b trial that has enrolled 31 patients with relapsed or refractory cHL who failed auto-HSCT and subsequent BV or who were transplant-ineligible.
Patients received pembrolizumab at 10 mg/kg every 2 weeks. The median duration of follow-up was 29 months.
The ORR was 58%, and the CR rate was 19%. The median duration of response had not been reached at last follow-up (range, 0.0+ to 26.1+ months), and 70% of responding patients had a response lasting 12 months or more.
The median PFS was 11.4 months (range, 4.9-27.8 months). The 6-month PFS rate was 66%, and the 12-month PFS rate was 48%.
The median OS was not reached. Six-month and 12-month OS rates were 100% and 87%, respectively.
The most common treatment-related AEs were diarrhea (19%), hypothyroidism (13%), pneumonitis (13%), nausea (13%), fatigue (10%), and dyspnea (10%).
The most common grade 3/4 treatment-related AEs were colitis (3%), axillary pain (3%), AST increase (3%), joint swelling (3%), nephrotic syndrome back pain (3%), and dyspnea (3%).
AEs leading to discontinuation were nephrotic syndrome (grade 3), interstitial lung disease (grade 2), and pneumonitis (grade 2). There were no treatment-related deaths.
