SHINE: Adding Ibrutinib to Treatment Improves PFS by 50% for Older Patients With Mantle Cell Lymphoma

Findings from the phase 3 SHINE trial could make ibrutinib the standard treatment option for older patients with mantle cell lymphoma (MCL), who often cannot tolerate chemotherapy or transplant strategies, according to study authors.

This article has been updated.

Adding ibrutnib to the current standard of care improved progression-free survival (PFS) by 50% for older patients with mantle cell lymphoma (MCL), according to findings presented Friday during the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.1

Findings from the phase 3 SHINE trial could make ibrutinib the standard treatment option for older patients with MCL, who often cannot tolerate chemotherapy or transplant strategies, according to the authors.

The study was simultaneously published in the New England Journal of Medicine (NEJM).2

The trial examined the effects of ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, when added to bendamustine-rituximab in patients with MCL who were at least 65 years of age, which is the typical age for patients with this disease. Rituximab was used for maintenance therapy.

MCL accounts for about 6% of patients with non-Hodgkin lymphoma; it causes B-lymphocytes in an area of the lymph node known as the mantle zone. In the United States, 4000 people are diagnosed with MCL each year; most are men over 65 years of age. Yet, as ASCO Chief Medical Officer and Executive Vice President Julie R. Gralow, MD, FACP, FASCO, noted, older patients are often left out of 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,” Gralow said in a statement. “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.”

Led by Michael Wang, MD, professor in the department of Lymphoma & Myeloma at The University of Texas MD Anderson Cancer Center in Houston, the study randomized 523 patients 1:1 at 203 international sites between May 2013 and November 2014. Results showed the following:

  • Patients randomized to receive ibrutinib along with standard of care (261 patients) had a median PFS of 80.6 months from the start of treatment until the disease worsened or the patient died; those randomized to receive placebo with standard of care (262 patients) had PFS of 52.9 months.
  • Primary end point was met, with hazard ratio (HR) favoring the ibrutinib arm, 0.75; one-sided P = .011.
  • The complete response rate was 65.5% in the ibrutinib and 57.6% in the placebo arm (P = .0567).
  • There was no difference in overall survival (OS), a secondary end point. Wang emphasized that the study was designed to examine PFS, and a study with OS as the primary end point would have been much larger.

Investigators reported that fewer patients in the ibrutinib arm needed a next treatment: 52 (19.9%) in the ibrutinib arm compared with 106 (40.5%) in the placebo arm needed additional therapy. In addition, 41 out of the 106 patients in the placebo group received a BTK inhibitor, with most receiving ibrutinib.

During a press conference ahead of his presentation, Wang said the difference of 2.3 years in PFS between patients whose regimen included ibrutinib and those who with standard of care was “significant.”

“This is truly meaningful, and really a remarkable achievement in the field for these patients,” he said.

He noted that the OS results needed to be viewed in context of the age of the patients. When patients were enrolled in the study 7 years ago, their median age was 70; today, the median age is 78, and half the patients are over 80 years. “So, they are going to die from other causes,” he said.

Wang has conducted multiple studies to treat MCL using newer therapies that have fewer toxic effects than traditional chemotherapy, which can be particularly hard for older patients to tolerate. Besides currently approved BTK inhibitors, Wang has noted the potential for venetoclax or investigational therapies such as pirtobrutinib.

Adverse events (AEs) of grade 3 or 4 were 81.5% and 77.3% in the ibrutinib vs. placebo groups, respectively. The safety profile was consistent with the known effects of ibrutinib and bendamustine-rituximab, according to investigators.

Asked whether this treatment regimen would be optimal for younger patients, Wang said for most, a more aggressive approach would still be preferred. In response to a question from The American Journal of Managed Care®, both Wang and Gralow acknowledged that some clinicians have had difficulty gaining insurer approval for ibrutinib in this setting, despite the availability of Wang’s abstract. However, both said after today, the data should put that question to rest.

Wang said that publication in NEJM should lead to inclusion in clinical guidelines, and that if clinicians attach the article with prior authorization requests, they should be approved. “That has been my experience,” he said.

Reference

  1. Wang M, Jurczak W, Jerkeman M, et al. Primary results from the double-blind, placebo-controlled, phase III SHINE study of ibrutinib in combination with bendamustine-rituximab (BR) and R maintenance as a first-line treatment for older patients with mantle cell lymphoma (MCL). J Clin Oncol. Abstr LBA 7502doi:10.1200/JCO.2022.40.17_suppl.LBA7502
  2. Wang M. Jurczak W, Jerkeman M, et al. Ibrutinib plus bendamustine and rituximab in untreated mantle-cell lymphoma. N Engl J Med. Published and updated June 3, 2022. DOI: 10.1056/NEJMoa2201817