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Addition of ibrutinib to chemoimmunotherapy shows promise for CLL
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The addition of ibrutinib to chemoimmunotherapy enhanced clinical activity in previously treated patients with chronic lymphocytic leukemia patients, according to study results.
The regimen also was well tolerated, results showed.
“Both ibrutinib and chemoimmunotherapy are very effective treatments for CLL, and their side effect profiles are different,” Jennifer R. Brown, MD, PhD, director of the CLL Center at Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School, told HemOnc Today. “It made sense to try them together to see if their efficacy would be enhanced.”
Jennifer R. Brown
Brown and colleagues randomly assigned patients to receive 420 mg daily ibrutinib (Imbruvica, Pharmacyclics) with bendamustine (Treanda, Cephalon) and rituximab (Rituxan, Genentech/Biogen Idec; n = 30) or with fludarabine, cyclophosphamide and rituximab (n = 3) for up to six 28-day cycles. However, the second arm closed early due to lack of enrollment.
The median age of the bendamustine and rituximab cohort was 62 years (range, 41-82) and 83.3% were male. Patients had received a median of two prior regimens (range, 1-3).
Median follow-up was 15.8 months.
The overall response rate was 93.3% (n = 28). Five patients (16.7%) achieved a complete response, and 20 (66.7%) achieved a partial response.
Twenty-one patients (70%) who responded well to therapy continued to receive ibrutinib monotherapy. Median follow-up for this cohort was 37.3 months, at which point 16 patients were still receiving treatment with ibrutinib.
When researchers included data from the extended follow-up the number of complete responders increased to 12 (40%), and the median time to complete response was 18.2 months (5.7-36.8). Fourteen patients (46.7%) achieved a partial response and two patients (6.7%) achieved a nodular partial response.
A majority of patients achieved PFS at 12 months (86.3%) and 36 months (70.3%).
Researchers noted the majority of adverse events were grade 1 or grade 2 and were similar to toxicities previously reported with the study treatment. The most frequent grade 3 or worse adverse effects were neutropenia (40%), maculopapular rash (10%), fatigue (10%), thrombocytopenia (6.7%), febrile neutropenia (6.7%) and cellulitis (6.7%).
Although the fludarabine, cyclophosphamide and rituximab arm closed early, researchers noted all three patients enrolled on this arm achieved a complete response.
“Ibrutinib can be safely given in combination with chemoimmunotherapy and the combination shows very promising activity,” Brown said. “Longer follow-up of this study to determine the true durability of response, as well as larger comparative trials to determine definitively whether the combination therapy is better than the therapy alone, are still needed.” – by Cameron Kelsall
For more information:
Jennifer R. Brown, MD, PhD, can be reached at Dana-Farber Cancer Institute, 450 Brookline Ave., M221, Boston, MA 02215; email: jennifer_brown@dfci.harvard.edu.
Disclosures: Brown reports a consulting role with Celgene, Genentech, Pharmacyclics and Roche. Other researchers report consultant roles and employment with, research funding from and equity ownership in Janssen and Pharmacyclics.
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