Targeted Therapy Triplet Shows Promise in R/R Richter’s Transformation and De Novo DLBCL

Anthony Mato, MD, MSCE, a hematologic oncologist and director of the CLL Program at Memorial Sloan Kettering Cancer Center, discusses the use of a triplet combination of the novel Bruton tyrosine kinase inhibitor (BTKi) DTRMWXHS-12, the mTOR inhibitor, everolimus (Afinitor) , and the IMiD pomalidomide (Pomalyst) for the treatment of relapsed/refractory Richter’s transformation (RT) and de novo diffuse large B-cell lymphoma (DLBCL).

According to Mato, the small-sponsor United States based company initially developed the inhibitor to be used as a backbone for other combination therapies. In vitro and in vivo screens were then developed to determine the right combination at the lowest possible dose in order to optimize efficacy while limiting toxicity.

The study followed a stepwise protocol. The inhibitor was first used as a monotherapy, then in combination with everolimus, then everolimus and pomalidomide were added. Both the Rt and DLBCL patient populations were heavily pretreated. According to Mato, the response rate for both groups was between 40% to 45%, and some durable remissions were achieved.

Mato says that this research supports hitting multiple pathways at once at lower doses. Currently, the supporting company is developing a single pill that contains all 3 therapies in order to improve patient adherence.