Moving towards biologically informed treatment strategies for T-cell lymphomas

The rarity and biological heterogeneity of the peripheral T-cell lymphomas has made subtype- and biomarker-driven approaches challenging to realize and even more challenging to evaluate in clinical practice. Out of necessity, treatment of T-cell lymphomas has historically been derivative of other aggressive lymphomas, utilizing intensive combination chemotherapy programs in the upfront setting and non-overlapping cytotoxic regimens upon relapse. However, due to tremendous work in understanding the oncogenic basis of these varied diseases, an increasing exploration of rational, targeted therapies is underway. Still, clinical successes have at times lagged behind pathobiological realizations, and there is an evolving need for biologically based, subtype-specific strategies in the clinic. Herein we propose a framework for future success that relies upon optimizing standard therapy in populations known to benefit from combination chemotherapy, building upon CHOP (or CHOP-like) induction with the CHOP + X model, exploring the use of targeted platforms in the relapsed and refractory setting, and designing biomarker-informed clinical trials that target-specific subhistologies and unique molecular subsets.