Patient Clinical Features Should Be Sequentially Considered to Determine Optimal Treatment in CLL

When deciding optimal frontline therapy for patients with chronic lymphocytic leukemia (CLL), providers must go beyond traditional factors such as clinical staging, according to an oral presentation given at the 35th Annual Chemotherapy Foundation Symposium in New York.¹

In order to optimize therapeutic sequencing among patients with CLL for whom treatment must be initiated, Kanti R. Rai, MD, stated that 5 patient aspects must be considered, which include previous treatment status, age, performance status (whether the patient is fit, less fit, or unfit as scored by ECOG or Karnofsky scores), 17p deletion or TP53 abnormalities, and IgVH mutation status.

According to Dr Rai, the 17p mutation status must be determined first for treatment-naive patients; patients with the 17p deletion del(17p) or TP53 mutation typically do not respond to chemoimmunotherapy, and even among patients who achieve a response, the duration is brief. Patients with mutated IgVH also have a significantly worse prognosis.

If it is determined that the patient does not have the 17p mutation, providers should take into consideration patient age (relatively younger patients less than 65 years vs. elderly patients older than 65 years) and whether the patient is fit, less fit, or unfit as determined by ECOG and Karnofsky scores. CLL typically occurs at a higher rate among elderly patients who tend to have a greater number of comorbidities, and their ability to handle the toxicity profiles of treatment must be taken into consideration.

Younger patients who are deemed to be fit and without del(17p) and with mutated IgVH, should receive chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) as frontline therapy.  Elderly patients who have similar features should initiate bendamustine plus rituximab (BR), or obinutuzumab plus chlorambucil as these regimens have more tolerable safety profiles.

Patients who are less fit without del(17p) should initiate BR or ibrutinib as first-choice treatment, and obtunutuzumab plus chlorambucil as second-line therapy.

Unfit patients with comorbidities with or without del(17p) should be treated with ibrutinib or obinutuzumab plus chlorambucil. Patients with del(17p) or with TP53 abnormalities should be started on ibrutinib.

Today patients with CLL have more treatment options than ever before. Dr Rai added, however, “[i]f the patient does not choose to [receive the appropriate] treatment recommendation, then an ongoing clinical investigational trial ought to be recommended.”

Read more of Cancer Therapy Advisor‘s coverage of the Chemotherapy Foundation Symposium (CFS) by visiting the conference page.

Reference

1. Rai KR. Optimizing therapeutic sequencing in CLL. Oral presentation at: 35th Annual Chemotherapy Foundation Symposium; New York; November 8-10, 2017.