Patients with chronic lymphocytic leukemia (CLL) will likely see a new standard of care based on outcomes in a phase 3 trial for patients treated with a combination of ibrutinib and rituximab.
A combination of ibrutinib and rituximab keeps patients with a common form of leukemia alive and disease-free longer than the current treatment regimen, according to a phase 3 trial results published today.
Patients with chronic lymphocytic leukemia (CLL) will likely see a new standard of care, researchers from Stanford Medicine said in a study published in New England Journal of Medicine. In the trial, 89.4% of those treated with the ibrutinib—rituximab combination had not seen their disease progress after 3 years, compared with 72.9% of those who had the traditional combination, with pairs of rituximab with fludarabine and cyclophosphamide.
As the study authors discussed, the current CLL treatment standard works for many patients but is terribly toxic, bringing severe myelosuppression and risk of infections due to immunosuppression of T cells. Patients taking the 2-drug combination studied in the trial reported less fatigue and fewer serious infections, in addition to the improved rates of progression-free survival (PFS) and overall survival (OS).
“These results will fully usher the treatment of chronic lymphocytic leukemia into a new era,” lead author Tait Shanafelt, MD, professor of medicine at Stanford, said in a statement. “We’ve found that this combination of targeted treatments is both more effective and less toxic than the previous standard of care for these patients. It seems likely that, in the future, these patients will be able to forego chemotherapy altogether.”
The study randomized a total of 529 patients, giving 354 patients the ibrutinib-rituximab combination and 175 the chemoimmunotherapy regimen. After 33.6 months, the hazard ratio (HR) for the study drug combination for PFS or death was 0.35 (95% CI, 0.22-0.56; P <.001). For OS, the study drug combo had an HR of 0.17 (95% CI, 0.05-0.54; P <.001). All patients were age 70 or younger.
The ibrutinib—rituximab combination was especially beneficial for patients without immunoglobulin heavy-chain variable region mutation, a group that historically did not respond as well to the standard treatment regimen.
Both groups had a similar rate of serious adverse events (grade 3 or higher), but infections were less common in the patients taking the study combination (37 patients compared with 32 patients).
The authors said the safety results were consistent with previous results of ibrutinib, said in pointing out the possible downsides of long-term use, pointed out that “indefinite use of ibrutinib therapy has bene associated with substantial expense.”
Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib—rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019;381:432-43. DOI: 10.1056/NEJMoa1817073.