Treatment of Chronic Lymphocytic Leukemia (CLL)

First-Line Treatment

The European Society for Medical Oncology recommends using venetoclax plus obinutuzumab for 12 months in patients with mutated IGHV and no del(17p)/TP53 mutations, or a second-generation BTK inhibitor continuously in patients with unmutated IGHV or del(17p)/TP53 mutations 1.
For patients without del(17p)/TP53 mutation, if IGHV is mutated, the first choice is venetoclax plus obinutuzumab for 12 months, with an alternative being a BTK inhibitor if venetoclax is contraindicated 1.
For patients without del(17p)/TP53 mutation, if IGHV is unmutated, the first choice is a continuous BTK inhibitor, with an alternative being venetoclax plus obinutuzumab for 12 months 1.

Treatment should not be started based solely on lymphocyte count or stage, but rather when patients meet criteria for "active disease" 1.
The International Workshop on Chronic Lymphocytic Leukemia recommends initiating therapy when patients have progressive marrow failure, massive splenomegaly, massive lymphadenopathy, progressive lymphocytosis, constitutional B symptoms, or autoimmune cytopenias poorly responsive to corticosteroids 1.

The European Society for Medical Oncology recommends obtaining FISH for del(17p) and TP53 mutation testing, IGHV mutational status, and a fitness assessment before initiating any therapy 1.

For patients with relapse >12-24 months after initial therapy, the same regimen can be repeated if it was well-tolerated and achieved a durable response 7.
For patients with relapse <12 months or refractory disease, an alternative drug class should be used, such as switching from chemoimmunotherapy to a BTK inhibitor or venetoclax-based regimen 7.

The European Society for Medical Oncology considers allogeneic stem cell transplantation the only potentially curative therapy for CLL, and recommends it for patients with del(17p)/TP53 mutation refractory to BTK inhibitors, patients refractory to both BTK inhibitors and venetoclax, and young, fit patients with del(11q) and early relapse 5, 6, 7.

The European Society for Medical Oncology recommends monitoring patients with CBC with differential every 2-4 weeks during chemoimmunotherapy, and every 2-4 months during BTK inhibitor therapy 2.
Physical examination for lymph node/spleen size should be performed at each visit, and bone marrow biopsy should only be performed to confirm complete remission 7.