While chemoimmunotherapy has been the cornerstone of frontline treatment for advanced disease in cases of relapse, several other therapeutic strategies are under development.

Promising therapeutic agents include:

• small molecules targeting signal transduction (PI3K inhibitors, BTK inhibitors)
• monoclonal antibodies targeting other cell surface proteins (CD19, CD47)
• epigenetic modifiers (EZH2 and HDAC inhibitors)
• immune checkpoint inhibitors (PD1, PD-L1, TIGIT)
• engineered CARs (CAR T- and CAR NK-cells)
• bispecific T-cell engagers
• antibody drug conjugates
• radioimmunoconjugates
• cancer vaccines
• immunomodulatory

Many of these agents are in advanced stages of development and have proven efficacy and manageable toxicity. Clinical trial participation is a good therapeutic consideration, particularly for patients who have progressed after two lines of therapy. ASCT and sometimes allogeneic stem cell transplantation is still a good option for certain patients with relapsed disease.