Adding Obinutuzumab and Weighing Genomic Risk With Continuous BTK Inhibition

Sameh Gaballa, MD, of Moffitt Cancer Center, asks when the faculty add obinutuzumab to acalabrutinib. M. Yair Levy, MD, of Texas Oncology–Baylor Charles A. Sammons Cancer Center, notes that the acalabrutinib plus obinutuzumab arm of ELEVATE-TN shows the longest 6-year progression-free survival among guideline-recommended options, but a hypothesis-generating subgroup analysis found no benefit in patients with a TP53 mutation, and the antibody adds infection risk. Andrew H. Lipsky, MD, of Columbia University Irving Medical Center, has not used the combination in a long time; Dr Gaballa rarely adds it except to debulk a patient quickly. On genomic risk, Dr Lipsky says a TP53 aberration is the one physician-directed decision, pointing to a Bruton tyrosine kinase (BTK) inhibitor, while unmutated immunoglobulin heavy chain variable region status matters more for time-limited therapy than for continuous BTK inhibition. Dr Levy agrees that complex karyotype, unmutated status, and 17p deletion shorten remissions but do not rule out any option.