Additive and synergistic inhibition of mantle cell lymphoma cell growth by combining olaparib with ibrutinib

Mantle cell lymphoma (MCL) presents a therapeutic challenge. The B cell targeting agent, ibrutinib, is currently one of the most effective second-line therapies for MCL, but frequently leads to development of drug resistance, and short overall survival time upon relapse. Olaparib targets tumor cells with deficiencies in single-strand DNA break repair and thus may slow the development of genetic drug resistance. We found that the olaparib-ibrutinib combination significantly inhibits cell culture growth compared to either drug alone in two genetically distinct MCL cell lines. Moreover, these inhibitory effects are either additive or synergistic, depending on genetic background. Culture growth is inhibited due to increases in apoptosis, cell death, and cell cycle arrest, and the magnitude of each is cell line dependent. The additive and synergistic inhibition of this combination additionally supports a therapeutic strategy involving lower dosing of each drug to reduce potential side effects.