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Exploring the Combination of PD-1 and CDK9 Inhibitors in Hematologic Cancers

By: Gavin Calabretta, BS
Posted: Tuesday, February 15, 2022

A phase Ib study published in Blood Advances analyzed the safety and efficacy of a combination treatment consisting of the PD-1 inhibitor pembrolizumab and the CDK9 inhibitor dinaciclib. According to Gareth Peter Gregory, MBBS, PhD, of Monash University, Australia, and colleagues, the regimen demonstrated modest efficacy in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL).

“Relapse during or after initial therapy is common, warranting alternative treatment options, among them targeted immunotherapy,” the authors commented. “[The KEYNOTE-155 study] evaluated the safety and efficacy of pembrolizumab plus dinaciclib in patients with [relapsed or refractory CLL, DLBCL, and multiple myeloma].”

The 72-patient study included both a dose-evaluation and signal-detection phase, the latter separating patients into cohorts based on disease type. All patients had relapsed or refractory disease, and continued treatment until disease progression or unacceptable toxicity was recorded. Those who discontinued or switched treatment before disease progression occurred were monitored until disease progression was documented.

Overall response rates of 29.4% (95% confidence interval [CI] = 10.3%–56.0%) and 21.1% (95% CI = 9.6%–37.3%) were observed in patients with CLL (five partial responses) and DLBCL (four complete responses, four partial responses), respectively. However, no response was seen in patients with multiple myeloma, and consequently, all were discontinued from treatment. In addition, the CLL cohort was also discontinued due to poor accrual. Median progression-free survival was measured at 5.2 months (95% CI = 1.4–12.4 months) in the CLL cohort, 2.1 months (95% CI = 1.8–2.6 months) in the DLBCL cohort, and 1.6 months (95% CI = 0.7–2.8 months) in the multiple myeloma cohort.

Throughout the study, the combination remained tolerable and produced no unexpected toxicities. The authors noted that although early discontinuation of treatment was a limitation of efficacy results, study data still encourage further exploration of PD-1 and CDK9 inhibitor combinations.

Disclosure: For full disclosures of the study authors, visit ashpublications.org.


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