The present invention provides a method and apparatus of handling in-device co-existence interference in a wireless communication environment. In one embodiment, a method includes detecting in-device co-existence interference between a LTE module and an ISM module in user equipment. The method further includes identifying subframes and corresponding HARQ processes in a set of subframes allocated to the LTE module which are affected by the ISM module operation. Additionally, the method includes reserving the remaining subframes and corresponding HARQ processes in the set of subframes for the LTE module operation. Furthermore, the method includes indicating to a base station that the remaining subframes and the corresponding HARQ processes are reserved for the LTE module operation to resolve the in-device co-existence interference. Moreover, the method includes receiving scheduling pattern indicating subframes and corresponding HARQ processes reserved for the LTE operation or derived DRX parameters from the base station based on the indication.