Anti-PD1 associated fulminant myocarditis after a single pembrolizumab dose: the role of occult pre-existing autoimmunity
Martinez-Calle N (1), Rodriguez-Otero P (2), Villar S (2), Mejías L (2), Melero I (3), Prosper F (2), Marinello P (4), Paiva B (5), Idoate M (2), San-Miguel J (2)
Multiple myeloma is a promising candidate for anti-PD1 checkpoint inhibitor therapy . 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. These positive results prompted the activation of phase III trials, which are currently underway in relapsed (KEYNOTE- 183/NCT02576977) and first line setting (KEYNOTE-185/NCT02579863). Immune- related adverse events (irAE) as a result of uncontrolled activation of autoreactive T- cells, 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 been published recently. Nivolumab patient database has revealed an incidence of myocarditis of 0.09% in over 20.000 patients already treated, although this may be an underestimation, only reflect symptomatic cases.
Myocarditis seems more frequent with the nivolumab-ipilimumab combination (0.27%), with two reports with a lethal outcome. 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 not with other checkpoint inhibitors, but with lenalidomide and dexamethasone.
CITATION Haematologica. 2018 Apr 12. pii: haematol.2017.185777. doi: 10.3324/haematol.2017.185777