Continuous Versus Intermittent Dosing Regimens for Pomalidomide in Relapsed/Refractory Multiple Myeloma

Summary

Lenalidomide has clinical activity in myeloma. The closely related compound, Pomalidomide, may have clinical activity in patients who have previously been treated with lenalidomide and who no longer respond to it. The mechanism of anti-tumor effects of these drugs has been attributed to several effects including anti-angiogenesis, immune activation, and anti-proliferative effects. Recent studies have suggested that these agents can mediate surprisingly rapid biologic effects on human monocytes and T cells. Our hypothesis is that the proximate effects of these drugs will be sensitive and quantitative surrogates of subsequent effects including activation of tumor antigen specific T cells as well as innate immune cells. Understanding the correlation between the pharmacodynamics of these effects with downstream activation using quantitative assays will facilitate the rational development of pomalidomide as immune-modulatory drug in diverse settings as well as its optimal development in myeloma therapy.

Timeline

Start

2011-06

Primary completion

2014-11

Completion

2014-11

Publications

• Sehgal K, Das R, Zhang L, Verma R, Deng Y, Kocoglu M, Vasquez J, Koduru S, Ren Y, Wang M, Couto S, Breider M, Hansel D, Seropian S, Cooper D, Thakurta A, Yao X, Dhodapkar KM, Dhodapkar MV. Clinical and pharmacodynamic analysis of pomalidomide dosing strategies in myeloma: impact of immune activation and cereblon targets. Blood. 2015 Jun 25;125(26):4042-51. doi: 10.1182/blood-2014-11-611426. Epub 2015 Apr 13.

Drugs

Indications