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J Clin Oncol: Efficacy of Ibrutinib + Rituximab vs. Placebo + Rituximab in the Treatment of Waldenstrm Macroglobulinemia: Results from the final analysis of the randomized Phase III iNNOVATE study

 Last Update: 2021-10-10
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The iNNOVATE study (PCYC-1127; NCT02165397) is a double-blind, randomized, placebo-controlled phase III clinical study that evaluates Ibrutinib + rituximab versus placebo + rituximab in the treatment of Waldenstrm giant balls Efficacy of proteinemia (WM)
.

In the preliminary analysis (median follow-up of 26.

The patient was diagnosed with symptomatic WM and had not been treated or previously treated; patients who had previously used rituximab had at least a mild response to the last rituximab-based treatment regimen
.

The primary endpoint is progression-free survival (PFS)

A total of 150 patients were included in the study, with 75 patients in each group

In the final analysis, the median progression-free survival (PFS) of the ibrutinib-rituximab group was significantly longer than that of the placebo-rituximab group (median did not reach 20 months; HR, 0.

Overall population PFS

Among patients with MYD88 ^WT / CXCR4 ^WT genotype, the 54-month PFS rates of the ibrutinib-rituximab and placebo-rituximab groups were 70% and 30%, respectively
.

^Among patients with MYD88 ^L265P / CXCR4 ^WT genotype, the 54-month PFS rates of the ^ibrutinib- rituximab and placebo-rituximab groups were 72% and 25%, respectively

Among patients with MYD88 ^WT / CXCR4 ^WT genotype, the 54-month PFS rates of the ibrutinib-rituximab and placebo-rituximab groups were 70% and 30%, respectively

The effect of MYD88/CXCR4 mutation on PFS

In the previously untreated patients, whether in the ibrutinib-rituximab or placebo-rituximab group, the 54-month PFS rate could not be assessed; the two groups had 48-month PFS The rates are 70% and 32% respectively
.

Among previously treated patients, the 54-month PFS rate of the ibrutinib-rituximab group was 68%, and the placebo-rituximab group was 20%, and the 48-month PFS rate was similar at 71 % And 20%

In the previously untreated patients, whether in the ibrutinib-rituximab or placebo-rituximab group, the 54-month PFS rate could not be assessed; the 48-month PFS in the two groups The rates are 70% and 32% respectively

Effect of previous treatment on PFS

In the final analysis, the ORR of the ibrutinib-rituximab group was significantly higher than that of the placebo-rituximab group (92% vs 44%)
.

The main response rate (partial response or better) of ibrutinib-rituximab was also significantly higher than that of placebo-rituximab (76% vs 31%; P <0.

In the final analysis, the ORR of the ibrutinib-rituximab group was significantly higher than that of the placebo-rituximab group (92% vs 44%)
.
The main response rate (partial response or better) of ibrutinib-rituximab was also significantly higher than that of placebo-rituximab (76% vs 31%; P <0.
0001)
.
Among patients with MYD88 ^WT / CXCR4 ^WT genotype, the ORR of the ibrutinib-rituximab group was 82%, while the ORR of the placebo-rituximab group was 56%
.
Similar results were observed in patients with MYD88 ^L265P /CXCR4 ^WHIM genotype and MYD88 ^L265P /CXCR4 ^WT genotype.
The ^{ORR of the Ibrutinib-} rituximab group was 100% and 94%, respectively, while the placebo- The ORR of the rituximab group was 48% and 43%, respectively
.
In the final analysis, the ORR of the ibrutinib-rituximab group was significantly higher than that of the placebo-rituximab group (92% vs 44%)
.
The main response rate (partial response or better) of ibrutinib-rituximab was also significantly higher than that of placebo-rituximab (76% vs 31%; P <0.
0001)
.
Among patients with MYD88 ^WT / CXCR4 ^WT genotype, the ORR of the ibrutinib-rituximab group was 82%, while the ORR of the placebo-rituximab group was 56%
.
In MYD88 ^L265P / CXCR4Similar results were observed in patients with ^WHIM genotype and MYD88 ^L265P / CXCR4 ^WT genotype.
The ^{ORR of the Ibrutinib-} rituximab group was 100% and 94%, respectively, while the placebo-rituximab The ORR of the group was 48% and 43%, respectively
.
^WT^WT^L265P^WHIM^L265P^WT

Efficacy evaluation

In the final analysis, the ibrutinib-rituximab group improved the hemoglobin of patients compared with placebo-rituximab (77% [58 / 75] vs 43% [32 / 75]; P<0.
0001 ), including the subgroup of patients with hemoglobin ≤11.
0 g/dL at baseline (n=94) (95% [42 / 44] vs 56% [28 / 50]; P<0.
001)
.

Neither treatment achieved a median OS (HR, 0.
81; 95% CI, 0.
33-1.
99; P=0.
6430)
.
The 54-month OS rates assessed by the two groups were similar, 86% (95% CI, 74-93) and 84% (95% CI, 71-92), respectively); the 48-month OS rate was 90% ( 95%CI, 79-95 years) and 88% (95%CI, 77-93)
.

Nine (12%) and 47 (63%) patients in the ibrutinib-rituximab group and placebo-rituximab group received follow-up treatment, respectively
.
Compared with placebo-rituximab, the median TTNT in the ibrutinib-rituximab group was significantly prolonged (not reached [95% CI, NE-NE] vs 18 months [95% CI, 11 -33];P<0.
001)
.
Nine (12%) and 47 (63%) patients in the ibrutinib-rituximab group and placebo-rituximab group received follow-up treatment, respectively
.
Compared with placebo-rituximab, the median TTNT in the ibrutinib-rituximab group was significantly prolonged (not reached [95% CI, NE-NE] vs 18 months [95% CI, 11 -33];P<0.
001)
.

TTNT

In summary, in the final analysis of the iNNOVATE study with a median follow-up of 50 months, regardless of the MYD88 or CXCR4 mutation status, previous treatment status, and patient characteristics, Ibritinib-rituximab showed superior clinical persistence Benefit
.
In the final analysis of the iNNOVATE study with a median follow-up of 50 months, regardless of MYD88 or CXCR4 mutation status, previous treatment status, and patient characteristics, Ibrutinib-rituximab showed superior sustained clinical benefit
.
In the final analysis of the iNNOVATE study with a median follow-up of 50 months, regardless of MYD88 or CXCR4 mutation status, previous treatment status, and patient characteristics, Ibrutinib-rituximab showed superior sustained clinical benefit
.

Original source:

Buske C, Tedeschi A, Trotman J, et al.
Ibrutinib Plus Rituximab Versus Placebo Plus Rituximab for Waldenström's Macroglobulinemia: Final Analysis From the Randomized Phase III iNNOVATE Study.
J Clin Oncol.
2021 Oct 4: JCO2100838.
doi: 10.
1200/JCO.
21.
00838 .
Epub ahead of print.
PMID: 34606378.

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