Anti-CD20 Antibodies Effective in Elderly CLL Patients

Alessandra Ferrajoli, MD

Elderly patients represent the largest group of patients with chronic lymphocytic leukemia (CLL) at approximately 86%, with a median age of CLL diagnosis of 72 years old, Alessandra Ferrajoli, MD, noted in an interview with OncLive.

This advanced age requires special considerations, according to Ferrajoli, who is an associate professor in the Department of Leukemia, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center. She said that the anti-CD20 monoclonal antibodies ofatumumab (Arzerra) and obinutuzumab (Gazyva) used in combination regimens with chlorambucil offer potential treatment options for elderly CLL patients.

The ofatumumab/chlorambucil combination was investigated in 447 patients with CLL in the COMPLEMENT 1 trial. All the patients in the trial were considered inappropriate for fludarabine-based therapy due to advanced age and/or comorbidities. The median age of patients was 69 years with 82% ≥65 years and/or having ≥2 comorbidities.

In the trial, ofatumumab and chlorambucil demonstrated a 9.3-month improvement in progression-free-survival (PFS) compared with chlorambucil alone. The overall response rate with the combination was 82% versus 69% with chlorambucil alone.

The CLL11 trial looked at the combination of obinutuzumab and chlorambucil compared with rituximab (Rituxan) and chlorambucil. In the stage II portion of the study, the overall response rate in the obinutuzumab arm was 79.6% compared with 66.3% with the rituximab arm. The complete response rate with obinutuzumab was 26.1% compared with 8.8% with rituximab. The median duration of response with obinutuzumab was 19.6 versus 9.7 months with rituximab.

OncLive: What special considerations need to be made when treating elderly patients with CLL?

In her Q/A with OncLive, Ferrajoli discusses the impact of these two trials, as well as other treatments that may be beneficial to the elderly CLL population.Ferrajoli: The clinical characteristics and presentation of the disease are quite similar between younger and older patients. What is different is the number of comorbidities. Older patients tend to have a higher number of comorbidities, and the comorbidities tend to be more severe. As a result, the tolerability to treatment is different.

The fitness and social circumstances of the patient should be considered. Importantly, the performance status and the comorbidities that could influence treatment effectiveness and tolerability should be considered. When we review the different options that are available for patients who are elderly and do not have a deletion of chromosome 17p, there are several possibilities. The combination of chemoimmunotherapy FCR (fludarabine, cyclophosphamide, rituximab) or BR (bendamustine and rituximab) is an option for patients who are more fit, are on the younger side, and have maintained renal function. This type of combination produces remissions in the majority of patients, with remission rates of 90% and very good remission duration.

Are there specific CD20 monoclonal antibodies that have shown positive results in the treatment of CLL?

For patients who are on the older side with comorbidities and are more frail, the combination of CD20-monoclonal antibodies with alkylating agents have been established as a good treatment option.The combination of a monoclonal antibody with chlorambucil was shown to be superior to chlorambucil alone. Among the different monoclonal antibodies, longer PFS rates are demonstrated with obinutuzumab, when added to chlorambucil. That combination tends to give a response rate around 60% to 70% and patients can achieve complete remission. There is even activity in minimal residual disease. It tends to be very well tolerated.

The combination of obinutuzumab plus chlorambucil was looked at in the CLL11 trial, in which it was compared with rituximab plus chlorambucil or chlorambucil alone. Obinutuzumab in combination with chlorambucil was shown to be superior.

What options are there for elderly patients with a deletion of chromosome 17p?

Where do you hope to see the treatment paradigm going for elderly patients with CLL?

The COMPLEMENT 1 trial examined chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with CLL. In this trial, the combination also performed better than chlorambucil alone.This is a unique group of patients. For these patients, the correct approach is the use of a B-cell receptor (BCR) inhibitor—either the BTK inhibitor ibrutinib or the P13K inhibitor idelalisib in combination with rituximab. Another agent that has potential is venetoclax.In the upcoming year, I think we will see a move toward more individualized treatment based on disease characteristics. We are already seeing separation based on patients with deletion of chromosome 17p, as well as with deletion 11q. I also expect to see a great increase in oral agents, which are particularly friendly to the elderly because they can be taken at home and require less of a disruption of routine.