Targeted Therapies Offer Attractive Treatment Approach for Elderly/Unfit Patients With CLL

The researchers outlined potential treatment options for this patient population since the emergence and uptake of targeted treatments.

With special considerations needed for the treatment of elderly or unfit patients with chronic lymphocytic leukemia (CLL), researchers have compiled the available evidence for using certain treatment approaches in this population, with an aim to improve survival and quality of life.

The researchers outlined potential treatment options for this patient population since the emergence and uptake of targeted treatments, offering preferred options that are a better fit for such patients, compared with more traditional chemotherapy approaches.

“In the era of targeted therapies, treatment of elderly/unfit patients with CLL must be a balance between efficacy and safety,” commented the researchers. “Although it is not possible to make direct comparisons between results of different studies, some considerations may guide the choice toward the best treatment option in elderly patients, considering both quality of life and life expectancy.”

Treatment approaches outlined by the group include chemoimmunotherapy, B-cell receptor (BCR) inhibitors, and venetoclax.

Chemoimmunotherapy approaches are decreasing in use among the elderly population as more chemotherapy-free options become available. For older patients (aged 65 years and older) that are considered fit, bendamustine with anti-CD20 antibodies, rituximab in particular, is still considered as an option. The bendamustine-rituximab combination has established a better risk-benefit profile than fludarabine–cyclophosphamide and rituximab, despite its inferior progression-free survival (PFS), because of its lower toxicity. Bendamustine has also been studied with obinutuzumab; together, the combination showed a complete response (CR) rate of 32% in patients that were a median age of 68 years. However, the combination also led to tumor lysis syndrome (TLS).

BCR inhibitors used in this patient population include ibrutinib, acalabrutinib, and a combination of idelalisib and rituximab. Approved for CLL in the relapsed/refractory setting, and for patients with del (17)/TP53 in the first-line setting, ibrutinib has shown superiority over chlorambucil frontline and ofatumumab, although there have been identified side effects of concern in elderly/unfit patients, including atrial fibrillation, hypertension, and bleeding.

In a trial of elderly/unfit patients aged a median of 74 years, acalabrutinib, with or without obinutuzumab, demonstrated improved overall survival rate (ORR) over chlorambucil–obinutuzumab, and in another trial showed superior PFS compared with bendamustine–rituximab and idelalisib-rituximab. In the latter trial, acalabrutinib alone was associated with serious adverse events in 29% of patients compared with 56% of patients treated with ibrutinib-rituximab and 26% of patients receiving bendamustine–rituximab.

The safety and efficacy of venetoclax in older patients was studied in a large, real-life trial of over 300 patients with relapsed/refractory CLL. Compared results in patients aged over 75 years and patients aged under 75 years, the study demonstrated no differences in ORR (81% vs 82%), 1-year PFS (79% vs 73%), or 1-year overall survival (77% vs 83%). Similar safety results were also found, with TLS being reported in 3% of patients in both age groups.


Fresa A, Autore F, Galli, et al. Treatment options for elderly/unfit patients with chronic lymphocytic leukemia in the era of targeted drugs: A comprehensive review. J Clin Med. 2021;10(21):5104. doi: 10.3390/jcm10215104