Frontline therapies for untreated chronic lymphoid leukemia

Therapy for chronic myeloid leukemia (CLL) is going through a major paradigm shift. Combination chemoimmunotherapy regimens have been the frontline therapies for CLL, whereas chlorambucil remained the standard frontline therapy for older patients (65 years or older) with CLL until recently. Monoclonal antibodies including rituximab, ofatumumab and obinutuzumab have been used for CLL therapy. Novel immunotherapeutics with chimeric antigen receptor (CAR) engineered T cells is rapidly migrating to clinical applications. Targeted therapies with small molecule inhibitors against Bruton tyrosine kinase (BTK) such as ibrutinib and acalabrutinib are playing a major role for treatment of patients with either treatment-naïve or refractory/relapsed CLL. Several major clinical trials including RESONATE-2, iLLUMINATE, ALLIANCE, ECOG 1912, CLL10, CLL14 as well as ibrutinib plus venetoclax have been ongoing in patients with untreated CLL. Frontline therapy of patients with untreated CLL appears to be shifting from chemotherapy to chemotherapy-free regimens. This review summarized latest development for frontline therapies of untreated CLL.