I have an 80-year-old male who saw me coming off a zanubrutinib trial for CLL, initially treated for anemia. He decided to decline the study after about 6 months and now his WBC is uptrending 36-->48, Hb hovering around 9, platelets are normal. He has a p53 mutation and IGVH is mutated. He is asymptomatic without palpable lymphadenopathy. I have not tested for BTK mutations. I am wondering what your thoughts are on when and what to start next line?
His platelets and Hgb are quite low given a modest elevation in WBC so I would think about Evan’s syndrome and be sure there is no evidence of concomitant MDS. If there is no evidence of either (he may need a marrow to sort things out) and he responded to zanubrutinib but came off by choice then I would restart zanubrutinib. If he came off due to side effects then I would suggest acalabrutinib. If he didn’t respond to or progressed on zanubrutinib then I would suggest venetoclax and obinutuzumab and it would be reasonable to start now but I would suggest a bone marrow biopsy and evaluation for hemolysis first since steroids may be adequate if his cytopenias are autoimmune in nature and obinutuzumab alone would be safer if there is a component of MDS.