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Ibrutinib plus rituximab improves PFS in Waldenström’s macroglobulinemia
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Combination therapy with ibrutinib and rituximab significantly prolonged PFS compared with rituximab plus placebo among patients with Waldenström’s macroglobulinemia, according to results of a study presented at ASCO Annual Meeting and simultaneously published in The New England Journal of Medicine.
“Rituximab [Rituxan; Genentech, Biogen], which is frequently used as monotherapy to avert chemoimmunotherapy associated toxic events, has shown considerable activity in patients with Waldenström’s macroglobulinemia, both among those who have received no previous treatment and among those with disease recurrence,” Meletios A. Dimopoulos, MD, professor and chairman of the department of clinical therapeutics at National and Kapodistrian University of Athens School of Medicine in Greece, and colleagues wrote. “Rituximab combinations with alkylating agents, proteasome inhibitors and nucleoside analogues are frequently recommended. More recently, single-agent ibrutinib [Imbruvica; Pharmacyclics, Janssen], a Bruton tyrosine kinase inhibitor, has also gained acceptance as a treatment for this condition.”
The researchers randomly assigned 150 patients (median age, 69 years; 33% aged 75 years or older) with Waldenström’s macroglobulinemia to receive either ibrutinib plus rituximab or placebo plus rituximab. Nearly half (45%) of patients had received no previous treatment.
PFS served as the study’s primary endpoint. Response rates, sustained hematologic improvements and safety served as secondary outcomes. Researchers also evaluated bone marrow samples for the mutational status of MYD88 and CXCR4.
At 30 months, 82% of the combined group achieved PFS compared with 28% of the placebo group (HR for progression or death = 0.2; 96% CI, 0.11-0.38). This benefit occurred independently of MYD88 or CXCR4 genotype.
Ibrutinib plus rituximab produced a higher rate of major response than placebo plus rituximab (72% vs. 32%; P < .001).
Nearly three quarters of patients assigned ibrutinib and rituximab experienced sustained increases in hemoglobin compared with less than half of those assigned placebo and rituximab (73% vs. 41%; P < .001).
The most common adverse events were infusion-related reactions, diarrhea, arthralgia and nausea.
The most frequent grade 3 or higher adverse events to occur more often in the combination therapy group included atrial fibrillation (12% vs. 1%) and hypertension (13% vs. 4%). Infusion reactions occurred less frequently in the combination group (1% vs. 16%), as did any grade of immunoglobulin M flare (8% vs. 47%). Both groups had similar rates of major hemorrhage (4%).
“We conclude that the addition of ibrutinib to rituximab represents a viable treatment approach for patients with Waldenström’s macroglobulinemia, both among those who have received no previous therapy and among those with disease recurrence, regardless of prognostic or genotypic factors,” Dimopoulos and colleagues wrote. – by Andy Polhamus
References:
Dimopoulos MA, et al. Abstract 8003. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Dimopoulos MA, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1802917.
Disclosures: Dimopoulos reports personal fees from Amgen, Celgene, Janssen, and Takeda outside the submitted work. Please see the study for all other authors’ relevant financial disclosures.