2018 ASCO Annual Meeting!
Session: Hematologic Malignancies—Plasma Cell Dyscrasia
Type: Poster Session
Time: Monday June 4, 8:00 AM to 11:30 AM
Location: Hall A
A phase 3 randomized study of pembrolizumab (Pembro) plus pomalidomide (Pom) and dexamethasone (Dex) for relapsed/refractory multiple myeloma (RRMM): KEYNOTE-183.
Hematologic Malignancies—Plasma Cell Dyscrasia
2018 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #30)
J Clin Oncol 36, 2018 (suppl; abstr 8021)
Author(s): Maria-Victoria Mateos, Hilary Blacklock, Fredrik Schjesvold, Albert Oriol Rocafiguera, David Simpson, Anupkumar George, Hartmut Goldschmidt, Alessandra Larocca, Daniel Wayne Sherbenou, Irit Avivi, Shinsuke Iida, Morio Matsumoto, Saad Zafar Usmani, Sundar Jagannath, Paula Rodriguez-Otero, Uma Kher, Mohammed Z.H. Farooqui, Jason Liao, Patricia Marinello, Sagar Lonial; University of Salamanca Hospital, Salamanca, Spain; Middlemore Hospital, Auckland, New Zealand; Oslo Universitetssykehus Rikshospitalet Postboks, Oslo, Norway; Hospital Universitario Germans Trias i Pujol, Barcelona, Spain; North Shore Hosp, Auckland, New Zealand; Wellington Blood and Cancer Center, Wellington, New Zealand; University of Heidelberg, Heidelberg, Germany; Myeloma Unit, Division of Hematology, University of Torino, Torino, Italy; University of Colorado Cancer Center, Denver, CO; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; National Hospital Organization, Shibukawa Medical Center, Shibukawa, Gunma, Japan; Levine Cancer Institute/Carolinas Healthcare System, Charlotte, NC; Mount Sinai Medical Center, New York, NY; Clínica Universidad de Navarra, Pamplona, Spain; Merck & Co., Inc., Kenilworth, NJ; Winship Cancer Institute of Emory University, Atlanta, GA
Background: KEYNOTE-183 (NCT02576977) evaluated pom + low-dose dex (SOC) ± pembro in patients (pts) with RRMM. Methods: Pts were randomized 1:1 to pembro (200 mg Q3W) + SOC (4 mg pom [d 1-21] + 40 mg dex [d 1, 8, 15, 22]) every 28 d vs SOC until progression (PD), unacceptable toxicity, withdrawal. Coprimary endpoints: PFS (2011 IMWG criteria), OS; secondary endpoints: safety, ORR. On July 3, 2017 based on interim data presented to the DMC, the FDA halted KEYNOTE-183. Results: 249/300 pts enrolled (125, pembro + SOC; 124, SOC) with median (range) age: 65 y (45-94) vs 67 y (22-90); 28 (22%) vs 17 (14%) pts had high-risk cytogenetics. Median (range) drug exposure was 123.5 d (2-477) vs 127 d (2-463); median 4.4 cycles. AEs with ≥5% difference between arms: neutropenia (38% vs 27%), nausea (17% vs 12%), pneumonia (23% vs 15%), ALT increase (10% vs 3%), headache (13% vs 4%). No SAEs had ≥5% difference between arms. In pembro + SOC arm, 21 (18%) pts had immune-mediated AEs: skin reaction (5%), pneumonitis (4%), hyperthyroidism (3%), infusion reaction (2%), myopathy (2%), myocarditis, iridocyclitis, hepatitis, Steven-Johnson syndrome (SJS; 1% each). 29 (23%) pts vs 21 (17%) died (16 from PD, 13 from AEs vs 18 from PD, 3 from AEs). 4 (3%) treatment related deaths occurred; 2 (1.5% [1 myocarditis, 1 SJS]) related to pembro. Median follow-up was 7.8 mo vs 8.6 mo. Median PFS: 5.6 mo vs 8.4 mo; HR, 1.53 (95% CI, 1.05-2.22); P= 0.98. Median TTP: 8.1 vs 8.7 mo. Median OS: not reached vs 15.2 mo; HR, 1.61 (95% CI, 0.91-2.85); P= 0.95. In a retrospective random forest analysis age, ECOG PS, disease stage, presence of plasmacytoma, double refractory status were more relevant contributors to death than treatment. A subsequent multivariable COX regression analysis showed age, ECOG, presence of plasmacytoma significantly contributed to risk of death. Age and presence of plasmacytoma were prognostic, while ECOG was prognostic and predictive of outcome with OS HR = 0.85 (ECOG 0) and OS HR = 2.3 (ECOG 1). Conclusions: The benefit-risk profile for combination of pembro, pom and dex is unfavorable for RRMM. Evaluation of T-cell subsets and cytokines along with long-term safety and survival follow-up is ongoing. Clinical trial information: NCT02576977
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.