Dr. Strati on the Investigation of Immunotherapy Combinations in Lymphoma

Paolo Strati, MD, assistant professor, Department of Lymphoma and Myeloma, Division of Cancer Medicine, Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, discusses several ongoing investigations aiming to improve upon current immunotherapy combinations, highlighting the introduction of novel regimens into the treatment landscape offollicular lymphoma (FL).

Clinical trials within the treatment of FL are primarily focused on exploring novel combinations to enhance the therapeutic activity of their respective treatment approaches in a biologically rational manner, Strati begins. One such treatment approach is evaluating the combination of lenalidomide (Revlimid) and rituximab (Rituxan).

Several trials in this field are exploring the utilization of lenalidomide/rituximab in combination with agents that can increase T cell engagement, such as mosunetuzumab-axgb (Lunsumio) and epcoritamab (Epkinly), Strati states. A randomized phase 3 trial (NCT02399085) is actively comparing the efficacy of mosunetuzumab combined with lenalidomide/rituximab, Strati notes. Furthermore, the phase 1/2 EPCORE NHL-2 trial (NCT04663347) is investigating the use of epcoritamab in combination with lenalidomide/rituximab for patients with relapsed, previously untreated indolent B-cell lymphoma, he adds.

Another avenue of interest within lymphoma is amplifying the activity of immunotherapy by promoting the repolarization of tumor-associated macrophages into an anti-tumoral phenotype, Strati continues. This can be achieved through the use of BTK inhibitors. Several trials are exploring the combination of lenalidomide/rituximab with BTK inhibitors such as acalabrutinib (Calquence), he expands.

Lastly, a growing focus of research in lymphoma is the potential shift away from utilizing chemotherapy and lenalidomide/rituximab as the standard of care, Strati says. This could be achieved by investigating the use of BTK inhibitors in combination with anti-CD20 monoclonal antibodies, he adds. The phase 2 ROSEWOOD trial (NCT03332017) evaluated zanubrutinib (Brukinsa) and obinutuzumab (Gazyva) vs obinutuzumab alone in patients with relapsed/refractory FL, Strati details. The study demonstrated a significant improvement in progression-free survival with the combination regimen, which was an unexpected result, Strati reports. These promising developments may provide effective, novel alternatives to standard chemotherapy and immunotherapies for patients in this space, he concludes.