Pembrolizumab Shows Promise in Multiple Myeloma
Monoclonal antibodies targeting PD-1 may be effective in multiple myeloma, according to early data from 2 clinical trials on pembrolizumab (Keytruda) presented at ASH 2015.
Pembrolizumab plus Lenalidomide/Dexamethasone
Among heavily pretreated patients with relapsed or refractory multiple myeloma, pembrolizumab was combined with lenalidomide (Revlimid) and dexamethasone (Decadron) in the phase 1 KEYNOTE-023 trial. The study was presented by Jesús San Miguel, MD, PhD, Medical Director, University of Navarra, Pamplona, Spain.
“Initial efficacy results show promising activity in heavily pretreated patients with relapsed/refractory multiple myeloma and support the continued development of pembrolizumab in these patients,” said Dr San Miguel.
Antitumor synergy is observed when anti–PD-1 antibodies and immunomodulatory drugs are used in combination, according to Dr San Miguel.
The trial enrolled 50 patients with relapsed or refractory multiple myeloma that progressed with ?2 previous therapies. All 50 patients were evaluable for safety and 17 were evaluable for efficacy. The dose-finding study determined the maximum tolerated dose to be pembrolizumab 200 mg given intravenously every 2 weeks in combination with lenalidomide 25 mg and low-dose dexamethasone 40 mg.
“We saw a response rate of 76% in the 17 patients who were evaluable, including 23% very good partial responses,” said Dr San Miguel. Among the 9 patients with lenalidomide-refractory disease, 5 achieved a partial response or better. The disease control rate, which indicated response or stable disease for at least 12 weeks, was 88%; only 6% of patients overall and 11% of patients with lenalidomide-refractory disease had progressive multiple myeloma.
The combination was well-tolerated, with an adverse event profile consistent with reports of pembrolizumab in solid tumors. Adverse events of any grade were reported by 72% of patients.
“We did not see any toxicities that were not expected,” said Dr San Miguel. “We observed that the safety profile is relatively good, but we are probably underestimating the side effects because the exposure to the drug has been limited.”
Pembrolizumab plus Pomalidomide/Dexamethasone
The drug was combined with pomalidomide and dexamethasone in a phase 2 study of 33 patients, in which 60% of patients responded.
Ashraf Z. Badros, MD, ChB, Professor of Medicine, University of Maryland, Baltimore, presented a phase 2 study of pembrolizumab 200 mg plus pomalidomide (Pomalyst) 4 mg and dexamethasone 40 mg in 33 patients with relapsed or refractory multiple myeloma who had at least 2 previous lines of treatment. All 33 patients were assessed for safety, and 27 patients were evaluable for response.
“The regimen shows promising antimyeloma activity, and has a predictable and manageable side-effect profile,” Dr Badros reported.
The objective response rates were 60% overall, 55% among patients with double-refractory disease, and 50% among patients with high-risk cytogenetics.
“It’s too early to look at progression-free and overall survival, but the signal we are seeing is quite impressive,” he said. At 6 months, the progression-free survival rate exceeds 75%, and the overall survival rate exceeds 90%.