August 28, 2018
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Comorbidities predict poor prognosis with ibrutinib for chronic lymphocytic leukemia

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Max J. Gordon

Comorbidities measured through the Cumulative Illness Rating Scale predicted poor prognosis among patients treated with ibrutinib for chronic lymphocytic leukemia, according to results of a retrospective analysis.

“It is important for patients to understand their other medical conditions may impact tolerance to leukemia-directed therapies and work with their physicians to choose the best therapy that they predict might lessen risk for adverse events and discontinuation,” Max J. Gordon, MD, from Knight Cancer Institute at Oregon Health and Science University, told HemOnc Today. “In other words, ibrutinib may not be for everyone, and certain patients may consider other therapies.”

Clinical trials have traditionally excluded patients with CLL and significant organ dysfunction, which limited information on how to manage this patient population.

Newer research has suggested that comorbidities correlate with treatment outcomes and can impact therapeutic approaches for CLL; however, an assessment of comorbidities in CLL has not been standardized, so the impact of comorbidities on treatment outcome has remained unknown.

Gordon and colleagues evaluated comorbidities via CIRS among 145 patients with CLL (median age, 70 years) who received ibrutinib (Imbruvica, Pharmacyclics).

Among the patients, 92% had an ECOG performance status of 0 or 1, and 50% had Rai stage 3 or 4 disease at ibrutinib initiation.

The median follow-up was 19 months (range, 2-54).

At the time of treatment initiation, the median total CIRS score was eight among all patients, seven among previously untreated patients and eight among patients with relapsed/refractory disease.

A total 60% of patients had a high burden of comorbidities and 54% had severe disease involvement of a single organ system.

Researchers observed an association between high burden of comorbidities — defined as a CIRS scoregreater than seven — and inferior median EFS (24 months vs. 37 months; P=.003) and 2year OS rate (79% vs. 100%; P=.005).

After adjusting for age, ECOG performance status, Rai stage, del(17p) status and number of prior therapies, a Cox proportional hazards model indicated EFS (HR = 1.07; P = .005) and OS (HR = 1.09; P = .03) worsened with every one-point increase in CIRS score.

Researchers observed similar results for patients with relapsed/refractory disease, and for patients older vs. younger than age 65 years.

Among all patients, 30 required a minimum of one dose reduction; 10 of these patients discontinued treatment due to adverse events. Thirty patients (21%) overall discontinued therapy with ibrutinib because of adverse events.

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Comorbidities appeared associated with an increased likelihood of reduced ibrutinib dose (OR = 3.64; 95% CI, 1.47-9.03) and of treatment discontinuation (OR = 3.3; 95% CI, 1.26-8.69).

After incorporating dose reductions and therapy discontinuation into the adjusted Cox model, CIRS score remained significant risk factor for mortality with every one-point increase.

Gordon noted the retrospective design as the study’s biggest limitation.

“Due to the retrospective nature of our study, we are not able to determine how exactly comorbidities exert this negative impact,” he said. “Also, our study was not designed to determine the optimal treatment approach for these patients.”

He added: “Prospective studies are needed to determine the optimal treatment approach for patients with CLL who have significant comorbidities. Both pharmaceutical and nonpharmaceutical (eg, geriatric consultation) could provide significant benefit.” – by Melinda Stevens

For more information:

Max J. Gordon, MD, can be reached at Knight Cancer Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97319; gordoma@ohsu.edu.

Disclosures: Gordon reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.