RESONATE™-2 (I vs Clb):
Study Design
OS, PFS, & Long-Term Data
HR Prognostic Factors
Studies With HR Patients
ORR

The only BTKi with 4 completed phase 3 studies in 1L CLL with high-risk patients1-6

Please see data for patients with and without high-risk factors for RESONATE™-2, E1912, ALLIANCE, and iLLUMINATE™.

IMBRUVICA® is the most studied BTKi in phase 3 trials with long-term data in high-risk CLL patients1-6

Patients with high-risk factors in the IMBRUVICA® monotherapy/combination arm across phase 3 studies

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TP53 mutationDel17pDel11qUnmutated IGHV
E1912
(IR vs FCR)
n=27 (9%)		E1912
(IR vs FCR)
n=78 (22%)		E1912
(IR vs FCR)
n=210 (75%)
iLLUMINATE™
(IG vs GCIb)
n=13 (12%)		iLLUMINATE™
(IG vs GCIb)
n=14 (12%)		iLLUMINATE™
(IG vs GCIb)
n=13 (12%)		iLLUMINATE™
(IG vs GCIb)
n=66 (62%)
RESONATE™-2
(I vs CIb)
n=11 (9%)		RESONATE™-2
(I vs CIb)
n=29 (21%)		RESONATE™-2
(I vs CIb)
n=58 (43%)
ALLIANCE
A041202
(I vs BR)
n=15 (9%)		ALLIANCE
A041202
(I vs BR)
n=9 (5%)		ALLIANCE
A041202
(I vs BR)
n=35 (19%)		ALLIANCE
A041202
(I vs BR)
n=77 (63%)

E1912: open-label, phase 3 trial in treatment-naïve patients (N=529) with CLL/SLL ≤70 years of age, randomized 2:1 to receive IMBRUVICA®* + rituximab† (n=354) or FCR‡§ (n=175). Patients with del 17p were excluded.5

iLLUMINATE™: phase 3, multicenter, open-label trial of 1L CLL/SLL patients (N=229) ≥65 years or 1L CLL/SLL patients <65 years of age with at least one of the following conditions: coexisting medical conditions, reduced renal function as measured by creatinine clearance <70 mL/min, or del 17p/TP53 mutation. Patients were randomized 1:1 to IMBRUVICA® 420 mg once daily until disease progression or unacceptable toxicity in combination with obinutuzumab (n=113) or chlorambucil in combination with obinutuzumab (n=116).2,5

RESONATE™-2: phase 3, multicenter, open-label trial of 1L CLL/SLL patients (N=269) ≥65 years of age who were randomized 1:1 to IMBRUVICA® 420 mg once daily until disease progression or unacceptable toxicity (n=136) or chlorambucil (n=133) for up to 12 cycles. Patients with del 17p were excluded.3,5

ALLIANCE A041202: phase 3, multicenter, open-label trial of 1L CLL patients (N=547) ≥65 years of age who were randomized 1:1:1 to IMBRUVICA® 420 mg once daily until disease progression or unacceptable toxicity (n=182), bendamustine at 90 mg/m2 on days 1 and 2 of each 28-day cycle for 6 cycles + rituximab (n=183), or IMBRUVICA® 420 mg once daily until disease progression or unacceptable toxicity + rituximab (n=182). It was coordinated by the Alliance for Clinical Trials in Oncology.4

The data from the ALLIANCE A041202 study have not been reviewed by the FDA and are not included in the IMBRUVICA® Prescribing Information.

420 mg once daily until disease progression or unacceptable toxicity.

†Rituximab initiated in cycle 2 for the IMBRUVICA® + rituximab arm and in cycle 1 for the FCR arm, and administered at 50 mg/m2 on day 1 of the first cycle, 325 mg/m2 on day 2 of the first cycle, and 500 mg/m2 on day 1 of 5 subsequent cycles, for a total of 6 cycles.

‡Fludarabine 25 mg/m2 on days 1, 2, and 3 of cycles 1-6.

§Cyclophosphamide 250 mg/m2 on days 1, 2, and 3 of cycles 1-6.

Abbreviations

1L=frontline, BR=bendamustine + rituximab, BTKi=Bruton's tyrosine kinase inhibitor, Clb=chlorambucil, CLL=chronic lymphocytic leukemia, del=deletion, FCR=fludarabine, cyclophosphamide, and rituximab, FDA=Food and Drug Administration, GClb=obinutuzumab + chlorambucil, HR=high-risk, I=IMBRUVICA®,  IG=IMBRUVICA® + obinutuzumab, IGHV=immunoglobulin heavy-chain variable region gene, IR=IMBRUVICA® + rituximab, SLL=small lymphocytic lymphoma, TP53=tumor protein 53.

References

1. Shanafelt TD, Wang XV, Hanson CA, et al. Long-term outcomes for ibrutinib–rituximab and chemoimmunotherapy in CLL: updated results of the E1912 trial [supplemental material]. Blood. 2022;140(2). 2. Moreno C, Griel R, Demirkan F, et al. Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(1):43-56. 3. Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373(25):2425-2437. 4. Woyach JA, Ruppert AS, Heerema NA, et al. Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL. N Engl J Med. 2018;379(26):2517-2528. 5. IMBRUVICA® (ibrutinib) Prescribing Information. 6. Barr PM, Owen C, Robak T, et al. Up to 8-year follow-up from RESONATE-2: first-line ibrutinib treatment for patients with chronic lymphocytic leukemia [supplemental material]. Blood Adv. 2022;6(11):3440-3450.