Treatment Advances Change the Landscape in Chronic Lymphocytic Leukemia

New chemoimmunotherapy drugs found to improve survival in patients with CLL.

Advances in chemoimmunotherapy for chronic lymphocytic leukemia (CLL) been changing the treatment landscape for patients afflicted with this disease, according to a study published in Oncology Research and Treatment.

Patients considered physically fit with or without mild comorbidities should be administered the standard treatment of fludarabine, cyclophosphamide, and rituximab (FCR). The results of a phase 2 clinical trial for FCR found a 6-year overall survival rate of 77% and failure-free survival rate of 51%.

Additionally, physically fit patients over 65-years-old, as well as patients with a higher risk of infections, should be given bendamustine and rituximab.

During a randomized CLL8 trial, a median observation time of 4.9 years had a 69% survival rate among patients administered FCR compared with 62% in patients treated with FC (hazard ratio (HR) 0.68, 95% confidence interval (Cl) 0.535-0.858; p = 0.001).

Patients with relevant and coexisting conditions should be administered chlorambucil with a CD20 antibody — preferably obinutuzumab, the study found. During the phase 3 CLL11 trial, 781 patients were enrolled with coexisting medical conditions (CIRS score of > 6 and/or creatinine clearance of < 70 ml/min).

The overall response rate (ORR) and complete response rate (CRR) was found to be the least successful in patients administered chlorambucil alone (ORR: 77% vs. 66% vs. 31%, CRR: 22% vs. 7% vs. 0%). The response was best when the drug was combined with the anti-CD20 antibody obinutuzumab to chlorambucil (G-Clb), followed by the combination of rituximab and chlorambucil (R-Clb).

Patients with del(17p) or TP53 mutations were found to respond poorly to conventional chemoimmunotherapy, because of the aggressive nature of the cancer is similar to acute leukemia.

Currently, the Bruton tyrosine kinase (BTK) and phosphatidylinositol-3-kinase (PI3K) inhibitors ibrutinib and idelalisib have the best efficacy in patients with high risk genomic alterations or refractory CLL.

When it comes to deciding between ibrutinib and idelalisib, decisions should be based off of the individual needs of patients suffering from 2 chronic simultaneous drugs and their associated medications, the study found. This is due to both agents having a toxicity profile that is typically tolerable amongst majority of patients.

Combining ibrutinib and idelalisib with rituximab or ofatumumab induced high response rates and improved PFS and OS in all of the patient groups. Patients with the best reported outcomes were those with del(17p)/TP53 mutations. However, these mutations retain their adverse prognostic impact as treatment outcomes were inferior in quality and duration compared with patients without these mutations.

Furthermore, treatment options for patients with late relapse should be based on their own individual needs. However, a chemoimmunotherapy approach is still considered the best treatment over kinase inhibitors, the study found.

Targeted drugs and their combinations are currently being explored in clinical trials with the potential to eradicate CLL cells, which could in turn lead to a CLL cure.