Advertisement

Immunotherapy in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma


Advertisement
Get Permission

Findings from the phase Ib KEYNOTE-013 and phase II KEYNOTE-170 trials reported in the Journal of Clinical Oncology by Armand et al indicated that pembrolizumab is highly active in relapsed or refractory primary mediastinal large B-cell lymphoma (PMBCL). The KEYNOTE-170 trial supported the 2018 accelerated approval of pembrolizumab for treatment of adult and pediatric patients with refractory PMBCL or who have relapsed after two or more prior lines of therapy.

Philippe Armand, MD, PhD

Philippe Armand, MD, PhD

As noted by the investigators, PMBCL is associated with frequent amplification and translocation events at 9p24.1 that result in tumor expression of programmed cell death ligands 1 and 2 (PD-L1 and PD-L2). Thus, investigators hypothesized that the disease may be susceptible to treatment with a programmed cell death protein 1 inhibitor like pembrolizumab.

Study Details

The analysis included 21 patients in KEYNOTE-013 and 53 patients in KEYNOTE-170 who received pembrolizumab at 200 mg every 3 weeks (10 mg/kg every 2 weeks in the first 10 patients in KEYNOTE-013) for a maximum of 35 cycles; up to 2 years; or until disease progression, unacceptable toxicity, or patient withdrawal. Patients in both studies had received a median of three prior lines of therapy, with all patients having received rituximab.

Responses

Objective response rates were 48% (complete responses in 7 patients, or 33%) among 21 patients in KEYNOTE-013 and 45% (complete responses in 7 patients, or 13%) among 53 patients in KEYNOTE-170. After a median follow-up of 29.1 months in KEYNOTE-013 and 12.5 months in KEYNOTE-170, the median duration of response was not reached in either study; durations of response were 1.9+ to 39.8+ months among responders in KEYNOTE-013 (78% of responders with response ≥ 12 months) and 1.1+ to 22.0+ months in responders in KEYNOTE-170 (76% of responders with response ≥ 12 months). At the time of analysis, no patient with a complete response experienced disease progression, with two patients exhibiting complete response for at least 1 year off therapy.

Median progression-free survival was 10.4 months in KEYNOTE-013 and 5.5 months in KEYNOTE-170, with 12-month rates of 47% and 38%, respecitvely. Median overall survival was 31.4 months in KEYNOTE-013 and not reached in KEYNOTE-170, with 12-month rates of 65% and 58%.

KEY POINTS

  • Objective responses were observed in 48% of patients in KEYNOTE-013 and 45% in KEYNOTE-170.
  • Median durations of response were not reached in either study.

Among 40 patients evaluable for 9p24.1 gene abnormality status, a significant increase in PD-L1 expression was observed with increasing levels of PDL1/PDL2 DNA copy number gain. Among 42 evaluable patients, PD-L1 expression was significantly associated with progression-free survival.

Adverse Events

Treatment-related events of any grade occurred in 71% of patients in KEYNOTE-013 and 57% of patients in KEYNOTE-170; grade 3 or 4 events occurred in 24% and 23%, with the most common being neutropenia in both trials (14% and 13%). One patient discontinued treatment due to treatment-related febrile neutropenia in KEYNOTE-013, and one discontinued treatment due to increased aspartate transaminase in KEYNOTE-170.

Adverse events led to death in three patients in KEYNOTE-170 (one patient each from Aspergillus infection, cardiac tamponade, and myocardial infarction), with none of the deaths being considered related to study treatment. Adverse events of interest occurred in 19% of patients in KEYNOTE-013 (including grade 3 myositis in one patient) and 11% in KEYNOTE-170 (including grade 4 pneumonitis in one patient). No patient in either study discontinued treatment or died as a result of an adverse event of interest.

The investigators concluded, “Pembrolizumab is associated with high response rate, durable activity, and a manageable safety profile in patients with [relapsed or refractory] PMBCL.”

Philippe Armand, MD, PhD, of Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The studies were supported by Merck Sharp & Dohme, a subsidiary of Merck & Co, and others. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
Advertisement

Advertisement



Advertisement