Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma

Abstract

• Treatment options for relapsed/refractory PMBCL are limited, and prognosis is generally poor.• Pembrolizumab had a manageable safety profile and promising antitumor activity in heavily pretreated rrPMBCL patients.Treatment options for relapsed/refractory primary mediastinal large B-cell lymphoma (rrPMBCL) are limited, and prognosis is generally poor (overall response rate [ORR] 0% to 25%; 2-year overall survival 15%). PMBCL frequently involves PD-1 ligand overexpression, potentially making PMBCL particularly susceptible to PD-1 blockade. We evaluated safety and antitumor activity of pembrolizumab, an anti-PD-1 antibody, in rrPMBCL as part of the KEYNOTE-013 multicohort phase 1b trial. At time of data cutoff, 18 patients (median age 30 years; median 3 prior lines of therapy) had been enrolled and treated, of whom 17 were included in the efficacy analyses. Eleven patients (61%) experienced drug-related adverse events (mostly grade 1-2); none discontinued treatment due to adverse events. ORR was 41% (7/17); 6 additional patients (35%) had stable disease. Of patients evaluable by imaging, 13 out of 16 (81%) had decreases in target lesions. With a median follow-up of 11.3 months, median duration of response was not reached. Two patients reached the maximum 2-year treatment duration and remain in remission. Median overall survival was not reached for treated patients overall; all responders were still alive at data cutoff. These results in heavily pretreated rrPMBCL patients demonstrate that PD-1 blockade with pembrolizumab has a manageable safety profile and promising antitumor activity. This trial was registered at www.clinicaltrials.gov as #NCT01953692. (Blood. 2017;130(3):267-270)

Pembrolizumab (Keytruda)

“…In a phase 1B study, 61 10 patients with relapsed or refractory primary mediastinal B-cell lymphoma, who had relapsed from or were ineligible for ASCT, were treated with pembrolizumab at 10 mg/kg every 2 weeks. Response was first assessed after 12 weeks, and then 8 weeks thereafter.…”

Cancer Immunology and Immunotherapy

“…The preliminary results reported 10 patients with relapsed refractory PMBCL who were treated with pembrolizumab; nine patients were evaluable for response. The ORR was 44% (4/9), with one patient achieving a CR and three achieving a PR (80).…”

Checkpoint-Inhibition bei Non-Hodgkin-Lymphom

“…Das PMBCL ähnelt in seinen Merkmalen nicht nur morphologisch dem HL, sondern auch dadurch, dass dabei ebenfalls eine Amplifikation von Locus 9p24.1 auftritt und es durch Genfusionen dazu kommen kann, dass die für PD-L1 und PD-L2 kodierenden Gene unter die Kontrolle des MHC-Klasse-IITransaktivators geraten [43]. Diese Region enthält die für PD-L1 und PD-L2 kodierenden Gene, wodurch es zu einer Überexpressi-on und in der Folge zu einer Immunevasion kommt [44]. Dieser Prozess kann durch den JAK2-Signalweg, der ebenfalls von der 9p24.1-Amplifikation betroffen ist, weiter verstärkt werden [45].…”