2018 ASCO Annual Meeting!
Session: Hematologic Malignancies—Plasma Cell Dyscrasia
Type: Oral Abstract Session
Time: Friday June 1, 2:45 PM to 5:45 PM
FDA analysis of pembrolizumab trials in multiple myeloma: Immune related adverse events (irAEs) and response.
Hematologic Malignancies—Plasma Cell Dyscrasia
2018 ASCO Annual Meeting
J Clin Oncol 36, 2018 (suppl; abstr 8008)
Author(s): Aviva C Krauss, Flora Mulkey, Yuan-Li Shen, Amy Rosenberg, Barry Miller, Theresa Carioti, Kimberly Scott, Nicole Gormley, Marc Robert Theoret, Rajeshwari Sridhara, Ann T. Farrell, Richard Pazdur; US Food and Drug Administration, Silver Spring, MD; U.S. Food and Drug Administration, Silver Spring, MD; National Cancer Institute at the National Institutes of Health, Bethesda, MD; US Food and Drug Admin, Bethesda, MD
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.
|ITT pop, N||125||124||151||150|
|Safety Pop, N||120||121||149||145|
|Pts with irAE||58%||45%||68%||44%|
|ORR in pts with|
2. Pomalidomide (POM), bortezomib, and low‐dose dexamethasone (PVd) vs bortezomib and low-dose dexamethasone (Vd) in lenalidomide (LEN)-exposed patients (pts) with relapsed or refractory multiple myeloma (RRMM): Phase 3 OPTIMISMM trial.