Details

Autor(en) / Beteiligte

• Badros, Ashraf
• Hyjek, Elizabeth
• Ma, Ning
• Lesokhin, Alexander
• Dogan, Ahmet
• Rapoport, Aaron P.
• Kocoglu, Mehmet
• Lederer, Emily
• Philip, Sunita
• Milliron, Todd
• Dell, Cameron
• Goloubeva, Olga
• Singh, Zeba

Titel

Pembrolizumab, pomalidomide, and low-dose dexamethasone for relapsed/refractory multiple myeloma

Ist Teil von

• Blood, 2017-09, Vol.130 (10), p.1189-1197

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• Programmed death 1 (PD-1) receptor and its ligand (PD-L1) facilitate immune evasion in multiple myeloma (MM). We hypothesized that pembrolizumab, PD-1-antibody, can enhance antimyeloma cellular immunity generated by pomalidomide, leading to improved clinical responses. In this single-center, phase 2 study, 48 patients with relapsed/refractory MM (RRMM) received 28-day cycles of pembrolizumab, 200 mg IV every 2 weeks, pomalidomide 4 mg daily for 21 days, and dexamethasone 40 mg weekly. Patients had a median of 3 (range: 2-5) lines of therapy, median age 64 (range: 35-83) years, and had received both an immune modulatory drug (IMiD) and proteasome inhibitor: (35 [73%] of 48) were refractory to both; (31 [70%]) had received an autologous transplant, and (30 [62%]) had high-risk cytogenetics. Adverse events grade 3 to 4 occurred in (19 [40%] of 48 patients), including hematologic toxicities (19 [40%]), hyperglycemia (12 [25%]), and pneumonia (7 [15%]). Autoimmune events included pneumonitis (6 [13%]) and hypothyroidism (5 [10%]), mostly ≤ grade 2. Objective responses occurred in (29 [60%] of 48) patients, including stringent complete response/complete response (4 [8%]), very good partial response (9 [19%]), and partial response (16 [33%]); median duration of response was 14.7 months. At median follow-up of 15.6 months, progression-free survival (PFS) was 17.4 months and overall survival was not reached. Analyses of pretreatment marrow samples revealed a trend for increased expression of PD-L1 in responding patients and longer PFS with increased T-lymphocyte infiltrates, irrespective of PD-1 expression. Pembrolizumab, pomalidomide, and low-dose dexamethasone have acceptable safety and durable responses in RRMM patients. This trial was registered at www.clincialtrials.gov as #NCT02289222. •This is the first trial to investigate PD-1 inhibitor, pembrolizumab, and an IMiD (pomalidomide) in MM with promising clinical efficacy.•PD-L1 expression on myeloma cells and PD-1 on marrow infiltrating T lymphocytes are potential biomarkers for efficacy of PD-1 blockade.