ZYDELIG® + rituximab (R) is proven to delay progression in relapsed CLL, including patients with high-risk features

ZYDELIG is indicated for relapsed chronic lymphocytic leukemia (CLL) in combination with rituximab in patients for whom rituximab alone would be considered appropriate therapy due to other comorbidities

Idelalisib (ZYDELIG) + rituximab is a PREFERRED treatment option in the NCCN Guidelines® for appropriate patients with relapsed/refractory CLL2*

Randomized, double-blind, placebo-controlled phase 3 trial (N=220)3

Key eligibility criteria

  • Relapsed within 24 months of their last treatment
  • Prior CD20 antibody-containing therapy, or ≥2 prior cytotoxic therapies
  • Not eligible for standard cytotoxic chemotherapy because of:
    • Comorbidities (CIRS score >6), or
    • Reduced renal function (CrCl <60 mL/min), or
    • Grade ≥3 neutropenia or thrombocytopenia from prior therapy

Therapy maintained until disease progression or unacceptable toxicity

Primary endpoint:
PFS

Secondary endpoints included:
ORR,§ DoR||

  • Trial stopped early for efficacy following first prespecified interim analysis

Studied in a clinically challenging patient population3-6

>40%
Had Del(17p) OR TP53 mutation
83%
Had Unmutated IGHV
88%
With total CIRS score >6
63%
Received AC, AP, and/or thrombolytics

Patient baseline characteristics3-5

 
ZYDELIG + R
(n=110)
Rituximab
(n=108)
Median age (range), years
71 (48-90)
71 (47-92)
Prior therapies,# median (range)
3 (1-12)
3 (1-10)
High-risk cytogenetics
%
%
Unmutated IGHV
83
85
Del(17p)
24
28
TP53 mutation
38
35
Del(11q)
34
30
Comorbidities
 
 
CIRS score, median (range)
9 (3-18)
8 (1-18)
Total CIRS score >6, %
88
82
CrCl, median (range)
61 (32-161)
67 (21-199)
CrCl <60 mL/min, %
45
37
Baseline cytopenias,** any grade
%
%
Anemia
75
72
Neutropenia
34
35
Thrombocytopenia
62
61
High disease burden
 
 
Rai stage 0/I-II/III-IV, %
0/31/64
1/26/65
Median Karnofsky performance status
80
80

Safety profile in relapsed CLL

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Adverse event monitoring
& management

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Healthcare professional
resources

Learn more

*Please see the complete version of the NCCN Guidelines® for CLL/SLL (V.3.2018) available on NCCN.org for specific recommendations.

†Patients received 8 doses of rituximab: First dose at 375 mg/m2, subsequent doses at 500 mg/m2 for weeks 2, 4, 6, 8, 12, 16, and 20.

‡PFS was defined as the interval from randomization to the first documentation of definitive disease progression confirmed by an IRC or death from any cause; definitive disease progression of CLL was based on standard iwCLL criteria, other than lymphocytosis alone.3,8

§ORR was defined as the proportion of subjects who achieved a CR or PR. Responses were assessed by an IRC.3

||DoR was measured from the onset of first documented response (CR or PR) to disease progression or death.7

¶First planned interim analysis at 50% of events.3

#Most common (>15%) prior regimens: BR (45%), FCR (34%), R monotherapy (31%), FR (17%), and Chl monotherapy (16%).

**Baseline anemia was defined as a hemoglobin level <11 g/dL, baseline neutropenia as an absolute neutrophil count <1 x 109/L, and baseline thrombocytopenia as a platelet count <100 x 109/L.8

AC=anticoagulant; AP=antiplatelet; BID=twice daily; BR=bendamustine, rituximab; Chl=chlorambucil; CI=confidence interval; CIRS=Cumulative Illness Rating Scale; CR=complete response; CrCl=creatinine clearance; DoR=duration of response; FCR=fludarabine, cyclophosphamide, rituximab; FR=fludarabine, rituximab; HR=hazard ratio; IGHV=immunoglobulin heavy-chain variable region gene; IRC=independent review committee; iwCLL=International Workshop on Chronic Lymphocytic Leukemia; NCCN=National Comprehensive Cancer Network; NR=not reached; OS=overall survival; ORR=overall response rate; PFS=progression-free survival; po=orally; PR=partial response; R=rituximab.

References:

  1. ZYDELIG® (idelalisib) [prescribing information]. Foster City, CA: Gilead Sciences, Inc.; rev January 2018.
  2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma V.3.2018. © National Comprehensive Cancer Network, Inc. 2018. All rights reserved. Accessed February 23, 2018. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
  3. Furman RR, Sharman JP, Coutré SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370(11):997-1007.
  4. Sharman JP, Coutré SE, Furman RR, et al. Efficacy of idelalisib in CLL subpopulations harboring del(17p) and other adverse prognostic factors: results from a phase 3, randomized, double-blind, placebo-controlled trial. Poster presented at: 50th Annual Meeting of the American Society of Clinical Oncology; May 30-June 3, 2014; Chicago, IL. Abstract 7011.
  5. Center for Drug Evaluation and Research. Idelalisib clinical review. Application number 206545Orig1s000.
  6. Barrientos JC, Ghia P, Pagel J, et al. Outcomes of anticoagulant or antiplatelet use in patients with chronic lymphocytic leukemia or indolent non-Hodgkin lymphoma in idelalisib trials. Poster presented at: American Society of Clinical Oncology; May 29-June 2, 2015; Chicago, IL.
  7. Data on file. Gilead Sciences, Inc. 2018.
  8. Furman RR, Sharman JP, Coutré SE, et al. Protocol for: Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370(11):997-1007.