February 2016, Vol. 5, No. 1

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Pembrolizumab Shows Promise in Multiple Myeloma

Jesus San Miguel, MD

ASH 2015, ASH Highlights

Jesus_SanMiguel98pxMonoclonal antibodies targeting programmed death-1 (PD-1) may be effective in multiple myeloma, according to early data on pembrolizumab presented at ASH.

In heavily pretreated relapsed/refractory patients, pembrolizumab was combined with lenalidomide/dexamethasone (Rd) in a phase 1 study with 50 patients, where a response rate of 76% was observed (Abstract 505). Pembrolizumab was also combined with pomalidomide/dexamethasone in a phase 2 study of 33 patients, where 60% of patients responded (Abstract 506).

The phase 1 KEYNOTE-023 study of pembrolizumab plus Rd was presented by Jesus San Miguel, MD, University of Navarra, Pamplona, Spain, who noted, “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.”

According to San Miguel, antitumor synergy is observed when anti–PD-1 antibodies and immunomodulatory drugs are used in combination.

The KEYNOTE-023 trial enrolled 50 patients with relapsed/refractory myeloma who progressed on 2 or more prior therapies (median of 4). 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 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 San Miguel. Among the 9 lenalidomide-refractory patients, 5 achieved a partial response or better. The disease control rate, indicating response or stable disease for at least 12 weeks, was 88%; only 6% of patients overall and 11% of lenalidomide-refractory patients had progressive disease.

The combination was well tolerated, with an adverse event profile that was consistent with reports of pembrolizumab in solid tumors. Adverse events of any grade were reported by 72% of patients. Side effects were consistent with the individual drug safety profiles for the approved indications.

“We did not see any toxicities that were not expected,” said San Miguel. “We observed that the safety profile is relatively good, but we are probably underestimating side effects because the exposure to the drug has been limited.”

Pembrolizumab plus Pomalidomide/Dexamethasone

Ashraf Z. Badros, MD, University of Maryland, Baltimore, presented the phase 2 study of pembrolizumab 200 mg plus pomalidomide 4 mg and dexamethasone 40 mg in 33 relapsed/refractory patients who had received at least 2 prior lines of treatment. All 33 patients were assessed for safety, and 27 were evaluable for response.

“The regimen shows promising antimyeloma activity and has a predictable and manageable side effect profile,” Badros reported.

The objective response rate for this regimen was 60% overall, 55% among double-refractory patients, 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, progression-free survival exceeds 75%, and overall survival exceeds 90%.

The Last Word - February 12, 2016

Personalized Medicine at FDA: 2015 Progress Report

One year after the initial observation by the Personalized Medicine Coalition (PMC) of an increased rate of personalized medicine approvals at the FDA Center for Drug Evaluation and Research (CDER), the most recent data show that the trend has continued, with oncology leading the way for the field.A new analysis [ Read More ]

San Antonio Breast Cancer Symposium - February 12, 2016

ESR1 Mutations Portend Worse Survival in ER+ Advanced Breast Cancer

A “liquid biopsy” was able to detect 2 mutations in the estrogen receptor 1 (ESR1) gene that predicted worse overall survival (OS) in women with estrogen receptor–positive (ER+), metastatic breast cancer who were originally enrolled in the BOLERO-2 clinical trial.The presence of a D358G and/or Y537S mutation in the ESR1 [ Read More ]