William G. Wierda, Jennifer Brown, Jeremy Abramson, Farrukh T. Awan, Greg Bociek, Daniel F. Boyer, Matthew J Cortese, Larry D. Cripe, Christopher R. D’Angelo, Elijah P. Darnell, Randall S. Davis, Herbert Eradat, Naseem Esteghamat, Lindsey Fitzgerald, Christopher D. Fletcher, Sameh Gaballa, Scott F. Huntington, Brad S. Kahl, Manali Kamdar, Thomas J. Kipps, Shuo Ma, Claudio A. Mosse, Shazia Nakhoda, Sameer A. Parikh, Peter A. Riedell, Andrew Schorr, Stephen Schuster, Madhav Seshadri, T. Shanafelt, Tanya Siddiqi, Andrea Sitlinger, Meghan C. Thompson, Chaitra Ujjani, Nina Wagner-Johnston, Jennifer A. Woyach, Mary Dwyer, Hema Sundar
Bruton tyrosine kinase inhibitors (BTKis) and BCL2 inhibitor (BCL2i)-containing regimens significantly improve survival outcomes in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Results from randomized clinical trials have demonstrated that time-limited treatment with BCL2i-containing regimens resulted in higher rates of undetectable measurable residual disease (uMRD) than BTKi monotherapy or chemoimmunotherapy (CIT). Pirtobrutinib (a noncovalent BTKi) and lisocabtagene maraleucel (CD19-directed CAR T-cell therapy) are newer options for relapsed or refractory disease after prior therapy with BTKi and BCL2i-contining regimens. Histologic transformation of CLL/SLL to diffuse large B-cell lymphoma (Richter transformation) is associated with a poor prognosis. Molecular analysis to determine whether there is clonal relationship between CLL/SLL and transformed diffuse large B-cell lymphoma is useful to select an appropriate treatment option. These NCCN Guideline Insights highlight significant updates to the NCCN Guidelines for the treatment of CLL/SLL and Richter transformation.