Ibrutinib (Imbruvica) combined with bendamustine-rituximab improved progression-free survival by 50% for older patients with newly diagnosed mantle cell lymphoma compared to patients who received a placebo plus bendamustine-rituximab, according to new research that will be reported at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.
Median PFS was 80.6 months with ibrutinib in combination with bendamustine-rituximab and rituximab maintenance, a 50% improvement over the group that received a placebo with bendamustine-rituximab and rituximab maintenance, which saw a median PFS of 52.9 months.
The complete response rate was 65.5% in the ibrutinib group and 57.6% in the placebo group.
There was no difference in OS between treatment groups at the time of the latest assessment of outcomes.
“The SHINE study is the first international phase III trial to show a positive impact of ibrutinib combined with standard-of-care treatment in this disease. The progression-free survival is substantially longer than the common treatment options used today, which is an important clinical advancement,” said lead author Michael Wang, MD, who is a professor in the department of Lymphoma & Myeloma at The University of Texas MD Anderson Cancer Center in Houston.
The time to the next treatment was longer in the ibrutinib arm compared with the placebo arm.
The number of patients who needed a next treatment was lower in the ibrutinib group compared with the placebo group: 52 (19.9%) and 106 (40.5%) patients received subsequent anti-lymphoma therapy in the ibrutinib and placebo groups, respectively; 41 out of the 106 patients (38.7%) in the placebo group received a subsequent Bruton tyrosine kinase inhibitor (mostly ibrutinib).
Grade 3 or 4 adverse events during treatment were 81.5% and 77.3% in the ibrutinib vs. placebo groups, respectively.
The safety profile of the combined treatment was consistent with the known profiles of ibrutinib and bendamustine-rituximab.
Quality of life was also similar in both groups.
Mantle cell lymphoma is a rare type of non-Hodgkin’s lymphoma, a cancer that affects the lymphatic system.
It develops from malignant B-lymphocytes within a region of the lymph node known as the mantle zone.
It affects men more than women, and more commonly in those older than 65 years of age.
Approximately one out of 200,000 individuals per year worldwide are diagnosed with mantle cell lymphomai; about 4,000 people a year are diagnosed with the disease in the United States.
There are several drug combinations used to treat mantle cell lymphoma and some are more intensive than others.
Because more intensive treatments tend to have more side effects, they are often reserved for younger patients or patients in good overall health.
Older people with mantle cell lymphoma can seldom tolerate intensive chemotherapy or stem cell transplantation due to the high degrees of toxicities associated with those therapies, leading to unsatisfactory outcomes in this group of people.
Hence, there is an urgent unmet need to develop additional treatment options for older people with mantle cell lymphoma.
Ibrutinib is a small molecule drug that inhibits immune system B-cell proliferation and survival by irreversibly binding to the protein Bruton's tyrosine kinase.
It is currently approved as a single agent for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy.
Bendamustine and rituximab are commonly given in combination for the treatment of older patients with mantle cell lymphoma.
The double-blind phase III SHINE trial randomly assigned 523 patients, age 65 or older with mantle cell lymphoma, to either ibrutinib plus bendamustine-rituximab (261 patients) or placebo plus bendamustine-rituximab (262 patients).
Both study groups had similar baseline characteristics. The median age of the patients in the study was 71 years. The median time that the patients were followed was seven years. The patients in the study continue to be followed for longer-term OS.
SHINE was supported by Janssen Pharmaceuticals NV & Pharmacyclics LLC, an AbbVie Company.
“Older people are generally underrepresented in clinical trials. Some lymphoma treatments, including intensive chemotherapy, targeted agents, or transplantation may have excessive toxicities in older patients, making them unsuitable choices for treatment. Patients with mantle cell lymphoma are often older and their inclusion in clinical trials can provide us with a better understanding of the balance between benefit and toxicity of treatments in their age group. Results from this trial bring new hope to newly diagnosed, older patients with this rare cancer who have had too few treatment options,” said ASCO Chief Medical Officer & Executive Vice President Julie R. Gralow, MD, FACP, FASCO.
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