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%.

ASH 2015, ASH Highlights - February 12, 2016

Another Study Shows Benefit with a Pediatric Regimen in Young Adults with ALL

A pediatric regimen achieves superior outcomes compared with adult regimens in adolescents and young adults with acute lymphoblastic leukemia (ALL). Several studies have already shown this outcome, and a multicenter phase 2 study presented at the meeting adds further confirmatory evidence in support of this approach. The multicenter phase 2 [ Read More ]

Editorial - February 12, 2016

The Coming Government Takeover of Drug Pricing ObamaCare provides the tools for a unilateral move against the industry the left loves to demonize

Hillary Clinton has plenty of allies as she demonizes drug-company profits and pushes for federal control over how drugs are priced. There’s a drug-pricing task force led by the White House and a similar Democrat-led effort in Congress. Many of the pharma industry’s proponents in Washington and on Wall Street [ Read More ]