trialsTrialPositive

RESONATE-2

RESONATE-2 showed that the oral BTK inhibitor ibrutinib kept untreated chronic lymphocytic leukaemia in check far longer than the old chemotherapy tablet chlorambucil in older patients, and helped them live longer, which brought targeted pills into first-line treatment of this leukaemia.

RESONATE-2 was an open-label phase 3 trial in patients aged 65 or older with previously untreated chronic lymphocytic leukaemia or small lymphocytic lymphoma, excluding those with 17p deletion. Patients were randomised to continuous ibrutinib or to chlorambucil, the chemotherapy standard for older patients at the time.

Ibrutinib significantly prolonged progression-free survival, the primary endpoint assessed by an independent review committee, and improved overall survival and response rates. The result led to approval of ibrutinib for first-line CLL in the United States in March 2016 and made continuous BTK inhibition a standard first treatment; long-term follow-up has confirmed durable disease control. Later trials (ELEVATE-TN, SEQUOIA) extended the approach to second-generation inhibitors.

Setting

Previously untreated chronic lymphocytic leukaemia or small lymphocytic lymphoma in patients aged 65 or older without 17p deletion: ibrutinib until progression against chlorambucil for up to twelve cycles

Phase

Phase 3

Sponsor

Pharmacyclics

Registry

NCT01722487

Headline result

Ibrutinib improved progression-free and overall survival over chlorambucil in older patients with untreated CLL; approved for first-line CLL in March 2016.

Started

2013-03

Reported

2015

Enrolled

269 enrolled

Outcomes

3top

In plain words

What these results mean for people, not percentages

269 enrolled

Progression-free survival (independent review committee)primarysurrogate endpoint

Median 18.9 months with Chlorambucil.
Ibrutinib: Not reached; median follow-up 18.4 months; 269 randomised.
"Not reached" means that, when the data were analysed, more than half of that group had not yet had the event, which is good news for that group.
A median is a midpoint: half the people did better than this and half did worse.
Put another way, the treated group had about 84 percent lower chance of the event at any given time (hazard ratio 0.16).

The p-value (<0.001) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.

Overall survival at 24 monthssurvival endpoint

98 vs 85 out of 100 alive at 24 months with Ibrutinib compared with Chlorambucil; 13 more per 100.
Roughly one extra person helped for every 8 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
Put another way, the treated group had about 84 percent lower chance of the event at any given time (hazard ratio 0.16).

The p-value (0.001) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.

Overall response rateresponse endpoint

86 vs 35 out of 100 had their tumour shrink with Ibrutinib compared with Chlorambucil; 51 more per 100.
Roughly one extra person helped for every 2 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.

The p-value (<0.001) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.

Caveats

These results apply to the people the trial enrolled: Previously untreated chronic lymphocytic leukaemia or small lymphocytic lymphoma in patients aged 65 or older without 17p deletion: ibrutinib until progression against chlorambucil for up to twelve cycles. People in a different situation may not see the same effect.
The trial selected people by a biomarker (17p); the result should not be assumed for people whose cancer does not have it.

Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.

269 enrolled.

Progression-free survival (independent review committee)primary

HR 0.16 · p <0.001

Download

Not reached; median follow-up 18.4 months; 269 randomised

Source

Overall survival at 24 months

HR 0.16 · p = 0.001

Ibrutinib98 of 100

Chlorambucil85 of 100

Download

Source

Overall response rate

· p <0.001

Ibrutinib86 of 100

Chlorambucil35 of 100

Download

Source

Endpoint	Arm	n	Value	HR (95% CI)	p	Source
Progression-free survival (independent review committee)primary	Ibrutinib	-	Not reached; median follow-up 18.4 months; 269 randomised	0.16	<0.001	link
	Chlorambucil	-	18.9 months	0.16	<0.001	link
Overall survival at 24 months	Ibrutinib	-	98%	0.16	0.001	link
Overall survival at 24 months	Chlorambucil	-	85%	0.16	0.001	link
Overall response rate	Ibrutinib	-	86%	-	<0.001	link
Overall response rate	Chlorambucil	-	35%	-	<0.001	link

Connected

8top

Trial
MURANO
Shares AbbVie (incl. ImmunoGen, Capstan), Chronic lymphocytic leukaemia, Small-molecule kinase inhibitors and the tag subtype-trials.
Trial
ASPEN (Waldenström macroglobulinaemia)
Shares Ibrutinib, Small-molecule kinase inhibitors and the tag subtype-trials.
Trial
VERONA
Shares AbbVie (incl. ImmunoGen, Capstan), Small-molecule kinase inhibitors and the tag subtype-trials.
Trial
SORAYA
Shares AbbVie (incl. ImmunoGen, Capstan) and the tag subtype-trials.
Trial
INTELLANCE-1
Shares AbbVie (incl. ImmunoGen, Capstan) and the tag subtype-trials.
Trial
AQUILA
Shares Johnson & Johnson and the tag subtype-trials.
Trial
MAIA
Shares Johnson & Johnson and the tag subtype-trials.
Trial
CARTITUDE-6
Shares Johnson & Johnson and the tag subtype-trials.

cancers

Chronic lymphocytic leukaemia Chronic lymphocytic leukaemia, first treatment

technologies

Small-molecule kinase inhibitors

drugs

ApprovedAlkylating agent (nitrogen mustard)

Chlorambucil · Leukeran

ApprovedSmall-molecule covalent BTK inhibitor (first generation)

Ibrutinib · Imbruvica

companies

AbbVie (incl. ImmunoGen, Capstan)Johnson & Johnson

people

Jan A. Burger

Evidence strength76/100 · Strong

How much and what kind of evidence, not how big the benefit. Click for the breakdown.

Phase 3+30
269 enrolled+12
Primary endpoint: time to progression or recurrence+14
Result: positive+15
No independent replication recorded0
A linked product is approved+5

Formula disclosed on the evidence page.

ProvenanceLast edited 2026-09-22 · Jude Gomila · Wave 2 corpus-only joins applied · diff · file

Sources & links

ClinicalTrials.gov NCT01722487

RESONATE-2

Setting

Phase

Phase 3

Sponsor

Pharmacyclics

Registry

NCT01722487

Headline result

Ibrutinib improved progression-free and overall survival over chlorambucil in older patients with untreated CLL; approved for first-line CLL in March 2016.

Started

2013-03

Reported

2015

Enrolled

269 enrolled

Outcomes

3top

In plain words

What these results mean for people, not percentages

269 enrolled

Progression-free survival (independent review committee)primarysurrogate endpoint

Median 18.9 months with Chlorambucil.
Ibrutinib: Not reached; median follow-up 18.4 months; 269 randomised.
"Not reached" means that, when the data were analysed, more than half of that group had not yet had the event, which is good news for that group.
A median is a midpoint: half the people did better than this and half did worse.
Put another way, the treated group had about 84 percent lower chance of the event at any given time (hazard ratio 0.16).

The p-value (<0.001) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.

Overall survival at 24 monthssurvival endpoint

98 vs 85 out of 100 alive at 24 months with Ibrutinib compared with Chlorambucil; 13 more per 100.
Roughly one extra person helped for every 8 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
Put another way, the treated group had about 84 percent lower chance of the event at any given time (hazard ratio 0.16).

The p-value (0.001) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.

Overall response rateresponse endpoint

86 vs 35 out of 100 had their tumour shrink with Ibrutinib compared with Chlorambucil; 51 more per 100.
Roughly one extra person helped for every 2 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.

The p-value (<0.001) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.

Caveats

These results apply to the people the trial enrolled: Previously untreated chronic lymphocytic leukaemia or small lymphocytic lymphoma in patients aged 65 or older without 17p deletion: ibrutinib until progression against chlorambucil for up to twelve cycles. People in a different situation may not see the same effect.
The trial selected people by a biomarker (17p); the result should not be assumed for people whose cancer does not have it.

Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.

269 enrolled.

Progression-free survival (independent review committee)primary

HR 0.16 · p <0.001

Download

Not reached; median follow-up 18.4 months; 269 randomised

Source

Overall survival at 24 months

HR 0.16 · p = 0.001

Ibrutinib98 of 100

Chlorambucil85 of 100

Download

Source

Overall response rate

· p <0.001

Ibrutinib86 of 100

Chlorambucil35 of 100

Download

Source

Endpoint	Arm	n	Value	HR (95% CI)	p	Source
Progression-free survival (independent review committee)primary	Ibrutinib	-	Not reached; median follow-up 18.4 months; 269 randomised	0.16	<0.001	link
	Chlorambucil	-	18.9 months	0.16	<0.001	link
Overall survival at 24 months	Ibrutinib	-	98%	0.16	0.001	link
Overall survival at 24 months	Chlorambucil	-	85%	0.16	0.001	link
Overall response rate	Ibrutinib	-	86%	-	<0.001	link
Overall response rate	Chlorambucil	-	35%	-	<0.001	link

Connected

8top

Trial
MURANO
Shares AbbVie (incl. ImmunoGen, Capstan), Chronic lymphocytic leukaemia, Small-molecule kinase inhibitors and the tag subtype-trials.
Trial
ASPEN (Waldenström macroglobulinaemia)
Shares Ibrutinib, Small-molecule kinase inhibitors and the tag subtype-trials.
Trial
VERONA
Shares AbbVie (incl. ImmunoGen, Capstan), Small-molecule kinase inhibitors and the tag subtype-trials.
Trial
SORAYA
Shares AbbVie (incl. ImmunoGen, Capstan) and the tag subtype-trials.
Trial
INTELLANCE-1
Shares AbbVie (incl. ImmunoGen, Capstan) and the tag subtype-trials.
Trial
AQUILA
Shares Johnson & Johnson and the tag subtype-trials.
Trial
MAIA
Shares Johnson & Johnson and the tag subtype-trials.
Trial
CARTITUDE-6
Shares Johnson & Johnson and the tag subtype-trials.

cancers

Chronic lymphocytic leukaemia Chronic lymphocytic leukaemia, first treatment

technologies

Small-molecule kinase inhibitors

drugs

ApprovedAlkylating agent (nitrogen mustard)

Chlorambucil · Leukeran

ApprovedSmall-molecule covalent BTK inhibitor (first generation)

Ibrutinib · Imbruvica

companies

AbbVie (incl. ImmunoGen, Capstan)Johnson & Johnson

people

Jan A. Burger

Evidence strength76/100 · Strong

How much and what kind of evidence, not how big the benefit. Click for the breakdown.

Phase 3+30
269 enrolled+12
Primary endpoint: time to progression or recurrence+14
Result: positive+15
No independent replication recorded0
A linked product is approved+5

Formula disclosed on the evidence page.

ProvenanceLast edited 2026-09-22 · Jude Gomila · Wave 2 corpus-only joins applied · diff · file

Sources & links

ClinicalTrials.gov NCT01722487

RESONATE-2

Outcomes

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