SAN FRANCISCO-Although it remains an incurable disease, patients diagnosed with chronic lymphocytic leukemia (CLL) who are treated with new targeted agents may have a normal life span, researchers suggested here at the first Cancer Survivorship Symposium (Abstract 7).
"The results from our study suggest improved overall survival for patients treated with ibrutinib (Imbruvica) compared with standard combination chemotherapy used in CLL," said John Allan, MD, Assistant Attending Physician and Assistant Professor of Medicine at Weill Cornell Medical College.
"Overall survival results suggest that ibrutinib may fundamentally change the natural history of CLL, such that treated patients may approach the life expectancy of the general population," he told OT at his poster presentation.
Results Analysis
In his presentation, Allan illustrated that treatment with ibrutinib in patients with newly diagnosed CLL showed better survival rates than treatment with former standard of care, chlorambucil-based chemotherapy. He and his colleagues performed a Bayesian Network Meta-Analysis conducted in line with the National Institute for Health and Care Excellence. They found that a 72-year-old person from the general population had a three-year overall survival of about 92 percent; patients treated with ibrutinib for initial therapy for CLL achieved a three-year survival of 96.6 percent at two years in one study and 98 percent survival at two years in a second study.
With treatment with ibrutinib, Allan noted, doctors were able to demonstrate humoral immune reconstitution in patients with CLL, recovery of normal B-cells, and partial reconstitution of humoral immune function.
"The decreased infection rate over time observed with ibrutinib treatment contrasts with the increased rate of severe and persistent infections associated with traditional combination chemoimmunotherapy, which suggests that ibrutinib may provide a valuable option to control CLL," Allan said. "Overall, single agent ibrutinib treatment appears to demonstrate a favorable safety profile while improving hematologic and immune function."
In reviewing the medical iterative, the researchers reported that long-term follow-up of ibrutinib indicated that treatment led to diminished toxicities over time, including Grade 2/Grade 3 cytopenias and infections. Dose reductions of ibrutinib occurred mainly in the first year of treatment, and toxicity leading to ibrutinib discontinuation diminished with continued treatment.
"In contrast [with other treatments], single agent ibrutinib led to manageable toxicities that were mainly mild to moderate in severity with low rates of dose reduction and low rates of discontinuations due to adverse events," Allan said.
'Excellent Activity'
In commenting on the study, Jacqueline Barrientos, MD, an investigator with the Feinstein Institute for Medical Research, Manhasset, New York, and Assistant Professor of Medicine at Hofstra North Shore-LIJ School of Medicine, said that newer treatments such as ibrutinib are transforming the way patients with CLL are being treated.
"Ibrutinib is the first in class Bruton's tyrosine kinase inhibitor that reported excellent responses in CLL patients," she told OT. "It is a targeted agent that affects the malignant clones' ability to survive and proliferate.
"The drug has excellent activity in terms of response rates (including in patients with refractory disease) and remission duration. Since it is a very well-tolerated drug, most patients like the option of taking a pill daily rather than coming for scheduled infusions of intravenous therapy, as there is no time lost from work or other activities," Barrientos said. "It currently is approved for relapsed or refractory disease and in patients with a known 17p deletion, and the Food and Drug Administration is evaluating its potential approval for patients older than 65 years old as front-line therapy based on the recent data showing superiority over chlorambucil monotherapy in this patient population."
She noted that in addition to ibrutinib, other agents are coming online in the treatment of CLL.
"Ibrutinib was the first orally available targeted agent approved in CLL patients, and since then we had a second drug approval with the PI3K delta inhibitor idelalisib," she stated. "Currently, the FDA is evaluating the approval of a third oral agent called venetoclax, which is a BCL2 inhibitor.
"All these approvals are changing the way we treat the disease, and people-that in the past didn't respond-are already living longer, thanks to these drugs," she said. "Moreover, patients that previously were too frail to tolerate any agents now have the opportunity to be treated with agents that are safer and better tolerated without affecting efficacy."
Barrientos continued: "For example, the third generation anti-CD20 monoclonal antibody obinutuzumab, in combination with chlorambucil, was evaluated in patients with multiple severe comorbidities (including patients with renal insufficiency that are traditionally excluded from clinical trials) and the study showed improved overall survival compared to chlorambucil monotherapy, so we may be at a time where we are changing the natural history of the disease with all these new agents."
Treatment Concerns
Allan said that changing CLL treatment to a chronic disease, requiring daily oral medication, may create other treatment concerns.
"Prolonged treatment and management of patients with CLL using novel oral agents such as ibrutinib require a new focus on adherence and patient management to support successful long-term outcomes," he said. "The advent of new targeted oral agents in CLL may suggest that we are on the cusp of moving away from a palliative chemotherapy-based care model where efficacy is frequently forfeited for acceptable tolerability."