Potential immune-related adverse events were grade 2 aggravated diarrhea and grade 2 radiation pneumonitis. No patient discontinued treatment and there were no treatment-related deaths.

With 41% (7/17) of patients showing an ORR, 2 patients had a complete response (CR) and 5 patients had a partial response (PR); 35% (6/17) of patients showed stable disease. No patient with an ORR received a stem cell transplant, although 2 patients with stable disease received an allogeneic stem cell transplant.


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The authors indicated that the ORR of 41% was higher than those reported in prior retrospective studies, where it ranged between 0% and 25%.

With median duration of response (DOR) not reached, DOR ranged from 2.3 or more to 22.5 or more months. DOR in 2 patients with CR was 2.3 or more and 20.5 or more months.

One patient with a CR and 1 patient with a PR remain in remission after the maximum treatment of 2 years.

“While these outcomes are encouraging overall, there exist few published studies specifically conducted in this rare patient population that can serve as accurate historical controls for efficacy comparisons with other treatment options for rrPMBCL,” the study authors wrote.

Dr Khan added that “an ORR of 30% is typical of single-agent novel therapies, across DLBCL subtypes. In the absence of a better alternative, one can consider pembrolizumab in rrPMBCL outside of chemotherapy.”

She explained that DLBCL is a heterogeneous disease and, based on molecular features, PMBCL is the non-germinal or activated B cell subtype. In the absence of predictive markers, PMBCL is treated like the germinal B cell subtype, which has better clinical outcomes.

A retrospective study of 180 patients with relapsed/refractory disease showed that salvage therapy resulted in significantly worse outcomes for patients with rrPMBCL — an ORR of 25% vs 48% for patients with relapsed/refractory DLBCL.2

Dr Khan indicated that data from this report provide a rationale for the use of pembrolizumab alone or with chemotherapy. “With these positive results, more innovative trials can be built with pembrolizumab in combination with other agents,” she said.

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A phase 2 study (KEYNOTE 170; ClinicalTrials.gov Identifier: NCT02576990) is evaluating single-agent pembrolizumab in rrPMBCL.

References

  1. Zinzani PL, Ribrag V, Moskowitz CH, et al. Safety & tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma. Blood. 2017 May 10. doi: 10.1182/blood-2016-12-758383 [Epub ahead of print]
  2. Kuruvilla J, Pintilie M, Tsang R, Nagy T, Keating A, Crump M. Salvage chemotherapy and autologous stem cell transplantation are inferior for relapsed or refractory primary mediastinal large B-cell lymphoma compared with diffuse large B-cell lymphoma. Leuk Lymphoma. 2008;49(7):1329-36.