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First-line iNNOVATE* study
The iNNOVATE study was a randomised, double-blind, placebo-controlled comparison of IMBRUVICA® + rituximab (I+R; n=75) vs. placebo + rituximab (PBO+R; n=75) in treatment-naïve or R/R patients with WM.[1]
iNNOVATE study primary endpoint*
Achieve long-lasting PFS with a chemotherapy-free approach for patients with 1L WM.[1]
Improved estimated PFS at 54 months†[1]
Improved PFS with I+R vs. PBO+R regardless of MYD88/CXCR4 genotype[1]
.png?width=1920&height=1080&format=webp&quality=50 "Chart 1")
iNNOVATE study secondary endpoints*
Time to next treatment (TTNT)[1]
- TTNT not reached with I+R vs. 18 months with PBO+R
- 87% vs. 29% (I+R vs. PBO+R) had not received subsequent treatment at 54 months*
Overall survival[1]
- Median OS not reached in either treatment arm
- OS rate at 54 months: 86% vs. 84% (I+R vs. PBO+R)
Response rates at 5 years[1][2]
- ORR: 92% vs. 44% (I+R vs. PBO+R) (p<0.0001)
Major response rate (≥partial response): 76% vs. 31% (I+R vs. PBO+R) (p<0.0001)
Higher response rates were observerd with I+R independent of prior treatment status or genotype[1]
- 91% (vs. 53% PBO+R) in TN; 93% (vs. 37% PBO+R) in previously treated
- Across genotypes, 94% (vs. 43% PBO+R) in MYD88L265P/CXCR4WT; 100% (vs. 48% PBO+R) in MYD88L265P/CXCR4WHIM; 82% (vs. 56% PBO+R) in MYD88WT/CXCR4WT
Hb levels[1]
- A greater proportion of patients receiving I+R vs. PBO+R had sustained Hb improvement (77% vs. 43%; p<0.0001)
Quality of life (QoL) data[3]
- Improved symptom-related QoL with I+R vs. PBO+R (PRO measures included FACIT-F, FACT-An total score and anaemia subscale score, and EQ-5D-5L visual analog scale and utility score)
Tolerability[1]
- 45% of patients treated with I+R continued treatment with IMBRUVICA® at a median follow-up of 50 months
Relapsed/refractory PCYC-1118e study
The PCYC-1118e study was an open-ended, multicentre, single-arm study of IMBRUVICA® in patients with relapsed/refractory WM (n=63).[4]
PCYC-1118e study primary endpoint
PCYC-1118e study secondary endpoints
Offer patients with R/R WM long-lasting survival outcomes with IMBRUVICA® monotherapy.[5]
PCYC-1118e: PFS in patients with R/R WM over time[5]
The majority of patients either achieved a major response or very good partial response (VGPR):[5]
- Major response rate: 79.4%[5]
- VGPR rate: 30.2%[5]
Variable | All | MYD88MUT | MYD88MUT
| MYD88WT
| p |
No. of patients | 63 | 36 | 22 | 4 | |
Overall response rate – no.(%) | 57 (90.5) | 36 (100.0) | 19 (86.4) | 2 (50.0) | < .0100 |
Major response rate – no.(%) | 50 (79.4) | 35 (97.2) | 15 (68.2) | 0 (0.0) | < .0001 |
Categorical responses – no.(%) | 6 (9.5) | 0 (0.0) | 3 (13.6) | 2 (50.0) | < .0001 |
Median time to response, months | 1.8 | 1.8 | 4.7 | NA | .0200 |
- Median serum IgM declined from 3,520 mg/dL to 821 mg/dL[5]
- Bone marrow disease involvement declined from 60% to 20%[5]
- Hb rose from 10.3 g/dL to 14.2 g/dL (p<0.001 for all comparisons)[5]
Evidence of efficacy in Bing-Neel syndrome
Bing-Neel syndrome is a rare complication of WM that occurs when WM cells infiltrate the central nervous system, causing neurological and ocular symptoms.[6]
The treatment goal for Bing-Neel syndrome is to reverse clinical symptoms and induce prolonged PFS.[6]
Due to the rarity of this syndrome and the lack of treatments, there are currently no standardised treatment guidelines for Bing-Neel syndrome.
Efficacy with IMBRUVICA®
IMBRUVICA® is indicated in patients with WM who have received at least 1 prior therapy, or in 1L treatment for patients unsuitable for chemoimmunotherapy.[7]
In a retrospective analysis:[8]
- 28 patients with Bing-Neel syndrome were treated with IMBRUVICA® between 2014 and 2018
- After 3 months of treatment, symptom and radiological improvements were reported in 84% and 57% of patients, respectively
- 2-year progression-free survival from treatment initiation was 80%, 2-year OS from treatment initiation was 81%, and 5-year OS from diagnosis was 86%
This content is intended for Healthcare Professionals only. IMBRUVICA® is licensed in the following indications:
- IMBRUVICA® as a single agent is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).
- IMBRUVICA® as a single agent or in combination with rituximab or obinutuzumab is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL).
- IMBRUVICA® as a single agent or in combination with bendamustine and rituximab (BR) is indicated for the treatment of adult patients with CLL who have received at least one prior therapy.
- IMBRUVICA® as a single agent is indicated for the treatment of adult patients with Waldenström’s macroglobulinaemia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemoimmunotherapy.
- IMBRUVICA® in combination with rituximab is indicated for the treatment of adult patients with WM.
Prescribing information may vary depending on approval in each country. Therefore, before prescribing any product, always refer to local materials such as the prescribing information and/or the Summary of Product Characteristics.
*Patients with confirmed symptomatic WM requiring treatment (N=150) were randomised 1:1 to receive either once-daily IMBRUVICA® + rituximab (n=75) or placebo + rituximab (N=75). Median follow-up was 50 months. †In the whole study population, the median PFS was not reached with IMBRUVICA® + rituximab vs. 20.3 months with placebo + rituximab (HR: 0.25 [95% CI: 0.15–0.42]; p<0.0001).[1]
1L=first line; BTKi=Bruton’s tyrosine kinase inhibitor; CI=confidence interval; EQ-5D-5L=EuroQol quality of life scale; FACIT-F=Functional Assessment of Chronic Illness Therapy – Fatigue; FACT-An=Functional Assessment of Cancer Therapy – Anemia; Hb=haemoglobin; HR=hazard ratio; I+R=IMBRUVICA® + rituximab; IgM=immunoglobulin M; ORR=overall response rate; OS=overall survival; PBO=placebo; PBO+R=placebo + rituximab; PFS=progression-free survival; PR=partial response; PRO=patient-reported outcomes; QoL=quality of life; R/R=relapsed/refractory; TN=treatment-naïve; TTNT=time to next treatment; VGPR=very good partial response; WM=Waldenström’s macroglobulinemia; WT=wild type.
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