A BTKi WITH MULTIPLE STUDIES IN 1L CLL INCLUDING HIGH-RISK PATIENTS
Please see data for high- and non-high-risk patients for RESONATE™-2, E1912, ALLIANCE, and iLLUMINATE™.
IMBRUVICA® studies included patients with unmutated IGHV, del17p, TP53 or del11q1,2
Patients with high-risk factors in the IMBRUVICA® monotherapy/combination arm across phase 3 studies3-6
| Unmutated IGHV | Del17p | TP53 | Del11q |
|---|---|---|---|
| E1912 (IR vs FCR) n=210 (75%) |
E1912 (IR vs FCR) n=27 (8%) |
E1912 (IR vs FCR) n=78 (22%) |
|
| iLLUMINATE™ (IG vs GClb) n=66 (62%) |
iLLUMINATE™ (IG vs GClb) n=14 (12%) |
iLLUMINATE™ (IG vs GClb) n=13 (12%) |
iLLUMINATE™ (IG vs GClb) n=13 (12%) |
| RESONATE™-2 (I vs Clb) n=58 (43%) |
RESONATE™-2 (I vs Clb) n=29 (21%) |
||
| ALLIANCE A041202 (I vs BR) n=77 (63%) |
ALLIANCE A041202 (I vs BR) n=9 (5%) |
ALLIANCE A041202 (I vs BR) n=15 (9%) |
ALLIANCE A041202 (I vs BR) n=35 (19%) |
E1912 was an 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. The primary endpoint was PFS as assessed by an IRC per iwCLL criteria.1
iLLUMINATE™ was a phase 3, multicenter, open-label trial of 1L CLL/SLL patients ≥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 (N=229). 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).1
RESONATE™-2 was a 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.1,5
ALLIANCE A041202 for Clinical Trials in Oncology group in collaboration with the National Clinical Trials Network (NCTN) was a 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 mg2 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.6
The data from the ALLIANCE A041202 study have not been reviewed by the FDA and are not included in the IMBRUVICA® Prescribing Information.
1L=frontline, ASH=American Society of Hematology, 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, I=IMBRUVICA®, IGHV=immunoglobulin heavy chain gene, IR=IMBRUVICA® + rituximab, iwCLL=International Workshop on Chronic Lymphocytic Leukemia, uIGHV=unmutated immunoglobulin heavy chain gene.
References:
- IMBRUVICA® (ibrutinib) Prescribing Information.
- Data on file.
- Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019;381(5):432-443.
- Moreno C, Griel R, Demirkan F, et al. Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia: primary results from the randomised phase 3 iLLUMINATE study. Lancet Oncol. 2019;20(1):43-56.
- 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.
- 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.