Pitfalls of Combining Novel Agents in Lymphoma.

OPINION STATEMENT: As our knowledge of lymphoma and its intricate signaling pathways has grown, so has the development of novel agents. While their mechanisms of action vary considerably, these therapies supplement and in some cases offer alternatives to standard chemotherapy. Initial studies have highlighted tolerable side effects though in the majority of instances limited efficacy when used as monotherapy. Research has focused on combining these novel agents to improve outcomes and perhaps offer refined treatment options. Novel combinations represent new territory, inherently dissimilar to combination chemotherapy with new pitfalls and challenges given their unique mechanisms of action. Though promising, it is crucial to consider the complex interplay that can occur. While there is potential for improved outcomes, there is also the possibility of unexpected toxicities. For this reason, it is critical that novel combinations be carefully considered and tested in clinical trials before widespread use. Thus far, research has shown that combination therapies are successful when not only avoiding overlapping toxicity but also capitalizing on synergy. We believe that more specific targets and an improved understanding of their off-/on-target effects will further successful novel combinations.