Publication | Closed Access
FDA analysis of pembrolizumab trials in multiple myeloma: Immune related adverse events (irAEs) and response.
20
Citations
0
References
2018
Year
Checkpoint InhibitionImmunologyPharmacotherapyImmunotherapyHematological MalignancyHematologyClinical TrialsRadiation OncologyPembrolizumab TrialsCell TransplantationNovel TherapyHealth SciencesTransplantationMedicineKeynote 185Fda AnalysisStem Cell TherapiesKeynote 183Cancer TreatmentImmune Checkpoint InhibitorMultiple MyelomaOncology
8008 Background: Development of irAEs with checkpoint inhibition may be associated with response in some disease settings. Methods: We evaluated overall survival (OS), safety and objective response rates (ORR) among patients who developed irAEs and those who did not in two trials of pembro in MM. KEYNOTE 183 (KN183) evaluated pomalidomide and dexamethasone (PomDex) with or without pembro in patients with relapsed/refractory (RR) MM, and KEYNOTE 185 (KN185) evaluated lenalidomide and dexamethasone (LenDex) with or without pembro in patients with newly diagnosed (ND) MM ineligible for autologous stem cell transplant. FDA placed both trials on clinical hold in July 2017 due to worse OS in the pembro-containing arms. Results: Using a June 2, 2017 data cut-off: median follow-up on KN183 was 8.1 months, 249 patients were randomized. There were 29 deaths in the pembro arm and 21 in the control arm, for an OS hazard ratio (HR) of 1.61 (95% CI: 0.91, 2.85). ORR was 34% in the pembro arm and 40% in the control arm. Median follow-up on KN185 was 6.6 months, 301 patients were randomized. There were 19 deaths in the pembro arm and 9 in the control arm, for an OS HR of 2.06 (95% CI: 0.93, 4.55). ORR was 64% in the pembro arm and 62% in the control arm. Neither trial showed a difference in time-to-progression between arms. In KN183, 58% of patients on the pembro arm developed an irAE, with an ORR of 37%, not significantly different than the 31% in those without an irAE. A trend was noted for improved ORR (49%) in those on the control arm (PomDex) with an irAE, compared to 33% in those without an irAE. In contrast, ORR in patients with NDMM in KN185 who developed an irAE were higher than in those who did not. Conclusions: The utility of immunotherapy in patients unable to mount adequate immune responses merits further study, as does the worse OS observed in both trials. KN183 KN185 Pembro+PomDex PomDex Pembro+LenDex LenDex ITT pop, N 125 124 151 150 Deaths 23% 17% 13% 6% ORR 34% 40% 64% 62% Safety Pop, N 120 121 149 145 Pts with irAE 58% 45% 68% 44% G≥3 irAE 18% 13% 36% 8% ORR in pts with No irAE 31% 33% 45% 53% irAE 37% 49% 73% 73% G≥3 irAE 29% 50% 70% 67%