Adding Bevacizumab to Chemoimmunotherapy Improves PFS in CLL

Adding bevacizumab to front-line chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab (PCR) may be safe and effective for the treatment of patients with chronic lymphocytic leukemia (CLL); however, this combination is associated with higher cardiotoxicity.¹

Although first-line chemoimmunotherapy has significantly improved the complete remission rate for patients with CLL, relapse continues to frequently occur, thus warranting the need for more effective treatment strategies.

Vascular endothelial growth factor (VEGF) plays a key role in the signaling pathways between CLL B-cells and their microenvironment, and low baseline VEGF levels predict a better response to chemoimmunotherapy. Therefore, researchers sought to evaluate the combination of an anti-VEGF agent with chemoimmunotherapy.

For the open-label, phase 2 trial, researchers enrolled 62 patients with previously untreated CLL. Patients were randomly assigned to receive bevacizumab plus PCR (PCR-B) or PCR alone as frontline treatment.

Results showed that 50% of patients who received PCR-B achieved complete remission compared with 33% of those who received PCR alone (P = .21). Patients who were treated with bevacizumab also had a significantly longer median progression-free survival (P = .04) and treatment-free survival (P = .05) vs PCR alone.

In terms of safety, 34% of patients in the bevacizumab arm reported grade 3 or 4 cardiovascular toxicity, particularly hypertension, compared with 0% of patients in the PCR group (P < .001). There were 7 cases of hypertension, 2 cases of congestive heart failure, 1 case of myocarditis, and 1 case of torsades de pointes.

The study also demonstrated treatment with bevacizumab was associated with reduced plasma levels of chemokine ligand (CCL)-3 and CCL-4.

Reference

1. Strati P, Shanafelt TD, Laplant B, et al. The addition of bevacizumab to chemoimmunotherapy prolongs progression-free survival in patients with chronic lymphocytic leukemia (CLL) through modulation of the microenvironment. Poster presentation at: AACR Annual Meeting 2016; April 16-20, 2016; New Orleans, LA.