Anti-PD1 associated fulminant myocarditis after a single pembrolizumab dose: the role of occult pre-existing autoimmunity

Abstract

Multiple myeloma is a promising candidate for anti-PD1 checkpoint inhibitor therapy.1–3 Results of phase I trials of pembrolizumab, in combination with lenalidomide or pomalidomide in relapsed/refractory patients have shown encouraging results. These trials showed a 35% and 65% response rate in patients already refractory to IMIDs with a median PFS of 7.2 and 14 months for the lenalidomide and pomalidomide combinations, respectively.4,5 These positive results prompted the activation of phase III trials, which are currently underway in relapsed (clinicaltrials.gov identifier 02576977) and first-line setting (clinicaltrials.gov identifier 02579863). Immune-related adverse events (irAE) as a result of uncontrolled activation of autoreactive T-cells,6 are the most important emerging safety issues of checkpoint inhibitors. Myocarditis is rare among the irAE; however, several cases of lethal immune-related myocarditis have recently been published.7–9 The Nivolumab patient database has revealed an incidence of myocarditis of 0.09% in over 20,000 patients already treated;7 however, this figure may be an underestimation since only symptomatic cases were recorded. Myocarditis seems to be frequent with the nivolumab-ipilimumab combination (0.27%), with two reports of a lethal outcome.8 To the best of our knowledge, no fatal cases have been reported with pembrolizumab or nivolumab as single checkpoint inhibitor agents. Here, we report a newly diagnosed multiple myeloma patient who developed a lethal immune-related myocarditis after a single dose of pembrolizumab, which was combined with lenalidomide and dexamethasone, not with other checkpoint inhibitors.