Table 2.
Selected agents that has anti-inflammatory properties used in CLL
| Agents | Primary mechanism of action | Potential benefits in CLL | Clinical efficacy – selected studies |
|---|---|---|---|
| Old agents | |||
| Glucocorticoids | Transactivation of anti-inflammatory genes and transrepression of pro-inflammatory genes | Lympholytic | Partial response in one third of patients. Mobilization from lymph nodes and spleen [55] High dose GC induced responses in 50% if patients with 17p deletion [58] |
| NSAID | Inhibition of (Cox-1) and Cox-2 | Inhibition of Cox-2 induces apoptosis of CLL cells | Concurrent use of aspirin and statins improved OS and PFS in patients with relapsed/refractory disease treated with chemo- immunotherapy [65] |
| Statins | HMG-CoA reductase inhibitors | Decrease synthesis of inflammatory cytokines, induces apoptosis of CLL cells | |
| Novel agents | |||
| Tyrosine Kinase Inhibitors | |||
| Dasatinib (Sprycel) | c-SRC and c-ABL kinase inhibitor | Targets also Lyn and BTK, impairs chemotaxis and adehesion of neutrophils | ORR of 20% in refractory/relapsed CLL [80] |
| Fostamatinib (R788) | Syk kinase inhibitor | Targets also ZAP70 | Limited data in patients with refractory/relapsed CLL [83] |
| GS1101 (CAL-101) | PI3Kδ inhibitor | Reduces secretion of inflammatory cytokines and chemokines | 37 patients with relapsed/refractory CLL enrolled in a Phase 1 study. > 50% reduction in lymphadenopathy in 60% of patients [106] |
| Ibrutinib (PCI-32765) | Irreversible BTK inhibitor | Inhibits BCR, TLR, BAFF, CD40 signaling pathways, reduces levels of CCL3 and CCL4 | ORR of 71% independent of genomic risk factors in 85 patients enrolled in a Phase 1b/2 study [86] |
| Immunomodulatory agents | |||
| Lenalidomide | Suppression of TNF-α levels | Immunomodulatory effects on proliferation of T cells, activation of NK cells and improvement in immunological synapse formation | ORR ranging from 32% to 65%. Elderly patients and patients with 17p benefit [97, 99-101] |
NSAID non-steroidal anti-inflammatory drugs; COX cyclooxygenase; BCR B-cell receptor; TLR toll-like receptor; B-cell activating factor; GC glucocorticoids; OS overall survival; PFS progression free survival; ORR Overall response rate.