3/31/2019 Lymphoma Hub | ASH 2018 | Results from the phase III iLLUMINATE trial on chemotherapy-free first-line treatment…

CLL/SLL

ASH 2018 | Results from the phase III iLLUMINATE trial on

chemotherapy-free rst-line treatment for CLL/SLL
Sylvia Agathou |  Dec 19, 2018

On Monday 3 December 2018, Oral Session 642 took place at the 60th American Society of
Hematology (ASH) Annual Meeting, San Diego, CA. During that session, results from the phase III
iLLUMINATE (PCYC-1130) trial (Abstract #691) were presented by Carol Moreno from the
Autonomous University of Barcelona, Barcelona, SP.

In this international, multicenter, randomized, phase III trial two combination regimens were investigated as rst-line
treatment for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Ibrutinib and
obinutuzumab combination was compared to chlorambucil and obinutuzumab for their e cacy and safety. This study is
one of the rst to compare a chemotherapy-free regimen to chemo-immunotherapy for CLL/SLL patients. The primary
endpoint of the study was progression-free survival (PFS) as assessed by an Independent Review Committee (IRC).
Secondary endpoints include overall response rate (ORR), overall survival (OS), safety, rate of undetectable minimal
residual disease (MRD), and PFS by IRC in the high-risk population.

Study design & baseline characteristics

N = 229 previously-untreated CLL/SLL patients, aged ≥ 65 or < 65 with ≥ 1 co-existing condition (CIRS > 6; CrCl < 70
ml/min; del(17p) or TP53 mutation)

Median age (range) = 71 (40−87) years

Randomized 1:1 dosing:

Ibrutinib & Obinutuzumab (Ibr-G; six 28-day cycles; n = 113 patients):

420 mg ibrutinib once daily until disease progression (PD) or unacceptable toxicity

1000 mg obinutuzumab split on Days 1−2, and on Day 8 and 15 (cycle 1) then on Day 1

Chlorambucil & Obinutuzumab (Clb-G; six 28-day cycles; n = 116 patients):

5 mg/kg on Days 1 and 15

1000 mg obinutuzumab split on Days 1−2, and on Day 8 and 15 (cycle 1) then on Day 1

After IRC-con rmed PD patients in this arm were allowed single-agent ibrutinib

Sixty- ve percent of patients from both arms had high-risk genomic features

Results

Median follow-up (range): 31.3 (0.2−36.9) months

Median PFS by bulky disease status:

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Ibr-G: not reached

Clb-G: 14.7 months

Median PFS by high-risk features:

Unmutated IGHV: not reached in the Ibr-G arm, 14.6 months in the Clb-G

Del(11q): not reached in the Ibr-G arm, 15.2 months in the Clb-G

Del(17p): not reached in the Ibr-G arm, 11.3 months in the Clb-G

Estimated PFS at 30 months:

Ibr-G: 79%

Clb-G: 31%

IRC-assessed ORR rates were (P < 0.01):

Ibr-G: 88%

Clb-G: 73%

IRC-assessed complete response (CR/CRi) rates were (P < 0.01):

Ibr-G: 19%

Clb-G: 8%

IRC-assessed partial response (PR) rates were:

Ibr-G: 65%

Clb-G: 66%

IRC-assessed stable disease (SD) rates were:

Ibr-G: 6%

Clb-G: 21%

In the high-risk population, IRC-assessed ORR rates were:

Ibr-G: 90%

Clb-G: 68%

In the high-risk population, IRC-assessed CR/CRi rates were:

Ibr-G: 14%

Clb-G: 4%

In the high-risk population, there was 85% reduction in risk of progression or death with Ibr-G

Among high-risk CLL patients without del(17p), there was 84% reduction in risk of progression or death with Ibr-G

Among unmutated IGHV patients without del(17p), there was 85% reduction in risk of progression or death with Ibr-G

Forty percent (n =46/116) of patients randomized to Clb-G crossed over to receive single-agent ibrutinib

No signi cant difference in OS was observed between Clb-G and Ibr-G patients at the median follow-up

In the Ibr-G arm, 70% of patients are still receiving ibrutinib treatment

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Salvage treatment for relapsed disease was required in 4% of patients in the Ibr-G versus 44% in the Clb-G group

Patients in the Ibr-G had a 94% reduction in the need for second-line therapy

Safety

Most frequent adverse events (AEs) of any grade:

Neutropenia: 43% in Ibr-G versus 63% in Clb-G

Thrombocytopenia: 35% in Ibr-G versus 25% in Clb-G

Diarrhea: 34% in Ibr-G versus 10% in Clb-G

Cough: 27% in Ibr-G versus 12% in Clb-G

Infusion-related reactions (IRRs): 25% in Ibr-G versus 58% in Clb-G

Arthralgia: 22% in Ibr-G versus 10% in Clb-G

Pyrexia: 19% in Ibr-G versus 26% in Clb-G

Anemia: 17% in Ibr-G versus 25% in Clb-G

Nausea: 12% in Ibr-G versus 30% in Clb-G

IRRs were less frequent in the Ibr-G group when compared to the Clb-G arm (P < 0.0001)

Conclusions

Ibr-G is an effective chemotherapy-free option for rst-line CLL/SLL treatment, including high-risk populations

Ibr-G provided greater progression and death risk reduction than Clb-G

Patients receiving Ibr-G achieved higher CR and undetectable MRD rates

Ibr-G was associated with a reduced risk of IRRs

This study indicates that Ibr-G led to superior PFS when compared to the current standard-of-care chemotherapy
regimens

References

1. Moreno C. et al. Ibrutinib + Obinutuzumab Versus Chlorambucil + Obinutuzumab As First-Line Treatment in Patients
with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (CLL/SLL): Results from Phase 3 iLLUMINATE.
Oral Abstract #691: ASH 60th Annual Meeting and Exposition, December 2018, San Diego, CA.

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