The
addition of ibrutinib to standard R-CHOP chemotherapy improved EFS, PFS
and OS among patients aged younger than 60 years with untreated
nongerminal center B-cell diffuse large B-cell lymphoma, according to results of a randomized, phase 3 study.
The
combination, however, appeared associated with increased toxicity and
resulted in worse outcomes among patients aged older than 60 years.
“The
interaction between age and toxicity was surprising [because] it was
not observed within the context of the phase 1 trial that we have
published,” Anas Younes, MD, chief of the lymphoma service and Steven
Greenberg chair at Memorial Sloan Kettering Cancer Center. “At the
present time, there is no obvious biological explanation, but this will
be addressed through planned extensive correlative studies. R-CHOP plus
ibrutinib is not commonly given to patients with other types of
lymphoma.”
DLBCL
accounts for as many as 40% of all lymphoma cases, making it the most
common form of lymphoma in the world. A previous phase 1 study appeared
to demonstrate the safety of ibrutinib (Imbruvica; Pharmacyclics,
Janssen) in combination with R-CHOP chemotherapy — which consists of
rituximab (Rituxan; Genentech, Biogen) plus cyclophosphamide, doxorubicin, vincristine and prednisone — among patients with untreated B-cell lymphoma, including DLBCL.
Younes
and colleagues specifically investigated whether ibrutinib improves the
efficacy of R-CHOP in patients with untreated nongerminal center B-cell
or activated B-cell diffuse large B-cell lymphoma.
Researchers
randomly assigned 838 patients (median age, 62 years; range, 19-88;
53.3% men) to R-CHOP with ibrutinib at 560 mg daily (n = 419) or with
placebo (n = 419) in a 21-day cycle for six or eight cycles, depending
upon institutional guidelines.
Three-quarters of the patients (75.9%) had the activated B-cell DLBCL subtype.
EFS
among the intent-to-treat population and patients with the activated
B-cell subtype served as the study’s primary endpoint. Secondary
endpoints included PFS, OS and safety.
Median follow-up was 34.8 months.
Results
showed that the addition of ibrutinib to R-CHOP did not improve EFS
compared with placebo and R-CHOP in the intent-to-treat population (HR =
0.93; 95% CI, 0.72-1.2) or the activated B-cell population (HR = 0.94;
95% CI, 0.7-1.27).
Ibrutinib
also did not increase PFS (HR = 0.91; 95% CI, 0.71-1.18), OS (HR =
0.99; 95% CI, 0.71-1.38) or rates of overall response (89.3% vs. 93.1%)
and complete response (67.3% vs. 68%) among the intent-to-treat
population.
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