FDA Expands Keytruda Label to Include Refractory or Relapsed Lymphoma

The FDA has granted accelerated approval to pembrolizumab (Keytruda, Merck), an anti-programmed death receptor-1 (anti–PD-1) therapy, for the treatment of adult and pediatric patients with refractory classical Hodgkin’s lymphoma (cHL) or those who have relapsed after three or more prior lines of therapy. Under the agency’s accelerated approval regulations, continued approval for this indication may be contingent on the verification and description of clinical benefit in confirmatory trials.

Pembrolizumab was approved for use in adults with refractory or relapsed cHL at a fixed dose of 200 mg and in pediatric patients at a dose of 2 mg/kg (up to a maximum of 200 mg). Pembrolizumab is administered intravenously every three weeks until disease progression or unacceptable toxicity occurs, or for up to 24 months in patients without disease progression.

The FDA’s accelerated approval was based on data from 210 patients with relapsed or refractory cHL enrolled in the open-label, nonrandomized KEYNOTE-087 study. The primary efficacy measures included the objective response rate (ORR), the complete remission rate (CRR), the partial remission rate (PRR), and the duration of response. Fifty-eight percent of the patients were refractory to their last prior therapies, including 35% with primary refractory disease and 14% whose disease was chemorefractory to all prior regimens. In addition, 61% of the patients had undergone prior allogeneic hematopoietic stem-cell transplantation (HSCT); 36% had undergone prior radiation therapy; and 17% had not received brentuximab.

The efficacy analysis showed an ORR of 69%, with a CRR of 22% and a PRR of 47%. The median follow-up period was 9.4 months. Among the 145 responding patients, the median duration of response was 11.1 months.

Pembrolizumab was discontinued because of adverse events (AEs) in 5% of 210 patients with cHL, and treatment was interrupted because of AEs in 26% of the patients. Fifteen percent of the patients experienced an AE requiring systemic corticosteroid therapy. Serious AEs occurred in 16% of the patients. The most common serious AEs included pneumonia, pneumonitis, pyrexia, dyspnea, graft-versus-host disease (GVHD), and herpes zoster. Two patients died from causes other than disease progression; one from GVHD after subsequent allogeneic HSCT and one from septic shock. The most common AEs included fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

Pembrolizumab is now approved for the following indications:

• Patients with unresectable or metastatic melanoma
• Patients with metastatic non–small-cell lung cancer (NSCLC) whose tumors have high programmed death ligand-1 (PD-L1) expression, as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and no prior systemic chemotherapy for metastatic NSCLC
• Patients with metastatic NSCLC whose tumors express PD-L1, as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy
• Patients with recurrent or metastatic head-and-neck squamous-cell carcinoma with disease progression during or after platinum-containing chemotherapy.
• Adult and pediatric patients with refractory cHL or those who have relapsed after three or more prior lines of therapy

Sources: Merck; March 14, 2017; and Keytruda Prescribing Information; March 2017.