Age-Related Recommendations in CLL Therapy

Kanti R. Rai, MD

Kanti R. Rai, MD

When treatment decisions are being made regarding chronic lymphocytic leukemia (CLL), patient age should be an important factor. CLL is a disease of the elderly, with more than 40% of all patients >75 years.¹Patients in this age group may have in excess of 4 comorbidities.²Although younger individuals can tolerate drugs with known toxicities to the kidneys, heart, liver, lungs, those drugs may not be appropriate for use even if they are needed in elderly patients with CLL. Many of today’s newer and more effective drugs are to be given for a long period of time.

However, nearly half (46%) of all patients with CLL are between the ages of 55 and 74 and have 3 comorbidities;^1,2therefore, most of these individuals have to be candidates for the modern therapies. On the other end of the spectrum, <10% of patients with CLL are younger in age (&le;54 years) and, if appropriate, can be given chemoimmunotherapeutic regimens, which may adversely affect the bone-marrow.

Choices for Therapeutic Agents

The therapeutic agents most often considered for patients with CLL are: (1) Bruton&rsquo;s tyrosine kinase (BTK) inhibitors such as ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib; (2) phosphoinositide 3-kinase (PI3K) inhibitors such as idelalisib (Zydelig) and duvelisib (Copiktra); (3) B-cell lymphoma-2 (BCL-2) antagonists such as venetoclax (Venclexta); and (4) anti-CD20 monoclonal antibodies such as obinutuzumab (Gazyva), rituximab (Rituxan), and ofatumumab. In addition, chemotherapy or chemo-immunotherapy regimens which include fludarabine, cyclophosphamide, and rituximab (FCR) as well as bendamustine plus rituximab (BR); and chlorambucil may be considered.

Other Relevant Factors

Although patient age and comorbidities are important to consider when deciding which therapeutic agents will be most appropriate, other factors such as the extent of symptoms, the level of tumor burden, presence of deletion 17p (del[17p]) or a TP53 abnormality must also be taken into consideration. If the patient has had prior treatments, we should consider whether he or she has been heavily pretreated because in those cases, not only bone marrow reserves but also reserves of other vital organs, may be severely compromised and thereby reduce the chances of achieving a good-quality remission with any proposed new therapy.

Symptomatic Elderly Patients

Preetesh Jain, MD, PhD

Preetesh Jain, MD, PhD

For patients with more advanced age, relatively compromised performance status, and symptomatic CLL, single-agent ibrutinib³or the combinations of obinutuzumab plus venetoclax⁴and obinutuzumab plus chlorambucil5 regimens are appropriate choices.

Is FCR OK?

For patients of relatively young age, those with no comorbidities, mutated IGVH, and without evidence of del(17p), chemo-immunotherapy such as FCR is appropriate.⁶

Symptomatic CLL With del(17p) or Abnormal TP53

For symptomatic CLL in patients with good performance status and del(17p) or abnormal TP53, ibrutinib or venetoclax with or without obinutuzumab should be recommended.^7,8

Conclusion

The pace of progress for improving CLL therapy has become very rapid during the past decade. Virtually all patients with poor prognosis now have some available therapies, which are effective. However, we have not found a definite and proven cure. The positive achievement, however, is that the patients with advanced age who represent classical CLL presentation and had been excluded from all experimental protocols for new therapies until a decade ago, are now the front and center of today&rsquo;s clinical trials. With this achievement, it is not unrealistic to expect that we are nearing a cure for this disease.

• Howlader N, et al. SEER Cancer Statistics Review, 1975—2008. Available at: seer.cancer. gov/csr/1975_2008/. Accessed May 2011.
• Yancik R. Cancer in the aged: an epidemiologic and demographic overview.Cancer. 1997;80(7):1273-1283. doi: 10.1002/(SICI)1097-0142(19971001)80:7<1273::AID-CNCR13> 3.3.CO;2-5.

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