RESONATE: trial | Bending the Curve: Trial by Trial

RESONATE

Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia

Population

Relapsed or refractory CLL or SLL with a short duration of response to therapy or adverse cytogenetic abnormalities (patients at risk for a poor outcome)

Design

Multicentre, open-label phase 3 study; 391 patients with relapsed or refractory CLL or SLL randomly assigned to daily ibrutinib or the anti-CD20 antibody ofatumumab. Secondary endpoints were overall survival and overall response rate.

Primary endpoint

PFS

Arms

Ibrutinib (experimental, n = 195): Ibrutinib orally once daily
Ofatumumab (control, n = 196): Ofatumumab (anti-CD20 antibody)

People

Byrd JC, RESONATE Investigators

PFSHR 0.22OSHR 0.43Δ 12-month OS+9 pointsΔ ORR+38.5 points

Show the numbers

Results reported for RESONATE
Endpoint	Analysis	Ibrutinib	Ofatumumab	Effect
PFSRandomly assigned patients (n=391); the abstract does not state the analysis population	primarymedian follow-up 9.4 monthsByrd 2014	88% at 6 mo	median 8.1 months	HR 0.22P<0.001Median PFS not reached in the ibrutinib group; 88% progression-free at 6 months. Hazard ratio is for progression or death in the ibrutinib group; no confidence interval in the abstract.
OSRandomly assigned patients (n=391); the abstract does not state the analysis population	primarymedian follow-up 9.4 monthsByrd 2014	90% at 12 mo	81% at 12 mo	HR 0.43P=0.005Hazard ratio for death in the ibrutinib group; no confidence interval in the abstract.
ORRRandomly assigned patients (n=391); the abstract does not state the analysis population	primaryByrd 2014	42.6%	4.1%	P<0.001An additional 20% of ibrutinib-treated patients had a partial response with lymphocytosis (abstract).

Results reported for RESONATE
Endpoint	Analysis	Ibrutinib	Ofatumumab	Effect
PFSRandomly assigned patients (n=391); the abstract does not state the analysis population	primarymedian follow-up 9.4 monthsByrd 2014	88% at 6 mo	median 8.1 months	HR 0.22P<0.001Median PFS not reached in the ibrutinib group; 88% progression-free at 6 months. Hazard ratio is for progression or death in the ibrutinib group; no confidence interval in the abstract.
OSRandomly assigned patients (n=391); the abstract does not state the analysis population	primarymedian follow-up 9.4 monthsByrd 2014	90% at 12 mo	81% at 12 mo	HR 0.43P=0.005Hazard ratio for death in the ibrutinib group; no confidence interval in the abstract.
ORRRandomly assigned patients (n=391); the abstract does not state the analysis population	primaryByrd 2014	42.6%	4.1%	P<0.001An additional 20% of ibrutinib-treated patients had a partial response with lymphocytosis (abstract).

Illustrative — modelled from reported values, not trial data. PFS, primary.

Show curves

Ofatumumab (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Ofatumumab
0	100.0%
5	65.2%
10	42.5%
15	27.7%
20	18.1%

Appears in

2013 Ibrutinib: BTK inhibition for relapsed CLL, approved in 2014

Sources

Byrd JC, Brown JR, O'Brien S, Barrientos JC, Kay NE, Reddy NM, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213-23.
PubMed DOI