IMBRUVICA-Based Combination Regimen Reduces Risk of Disease Progression or Death in Older Mantle Cell Lymphoma Patients

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The Janssen Pharmaceutical Companies of Johnson & Johnson released the primary results of the Phase 3 SHINE study (Abstract #7502) on Friday. The results showed that the combination of once-daily oral IMBRUVICA® (ibrutinib) plus bendamustine-rituximab (BR) and rituximab maintenance reduced the risk of disease progression or death by 25% compared to patients who got a placebo plus BR and rituximab (MCL). This study is one of the biggest clinical trials ever done for first-line MCL and the first for a Bruton’s tyrosine kinase inhibitor (BTKi).  During the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, the data will be presented in an oral session and discussed in a press briefing. The data were also published in The New England Journal of Medicine today. The data will also be presented orally at the 2022 Annual Congress of the European Hematology Association (EHA).

MCL is an aggressive, rare type of non-Hodgkin lymphoma (NHL) that is hard to treat and cannot be cured.

It usually affects people over the age of 65, who usually can’t handle intensive chemoimmunotherapy and stem cell transplantation. This leads to bad clinical results and makes it important to find other ways to treat these patients. 

The Phase 3 SHINE (MCL3002) study (NCT01776840), which was run by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie Company, enrolled 523 patients with newly diagnosed MCL who were 65 years or older.

All of the participants were given either IMBRUVICA® (560 mg orally every day until progression or unacceptable side effects) or a placebo plus BR for a maximum of six 28-day cycles. Those who had a complete response (CR) or partial response (PR) kept getting rituximab maintenance therapy every other cycle for a maximum of 12 more doses.

IMBRUVICA or a placebo was given every day until the disease got worse or the side effects were too bad.

The main goal of the SHINE study, progression-free survival, was reached (PFS). Some of the most important results of the Phase 3 SHINE study are:

With a median follow-up of 84.7 months, the IMBRUVICA plus BR and rituximab maintenance combination showed a statistically significant and clinically meaningful 2.3-year improvement in median PFS (6.7 years) compared to BR (4.4 years).

Compared to patients who were treated with BR and rituximab maintenance, this is a 50% improvement (stratified hazard ratio [HR]: 0.75, 95 percent confidence interval [CI]: 0.59-0.96; p = 0.011).

  • CR, time-to-next-treatment (TTNT), overall survival (OS), and overall response rate were all-important secondary endpoints (ORR).
  • 171 (65.5%) of the patients in the IMBRUVICA® plus BR arm and 151 (57.6%) of the patients in the placebo arm reached CR (p = 0.057).
  • The rates of objective response were the same in both groups (89.7% for IMBRUVICA® plus BR and 88.5 % for the placebo).
  • In the IMBRUVICA plus BR group, the median TTNT was not reached, but it was 92 months in the placebo plus BR group (p 0.001).
  • OS was the same in both treatment groups, and the middle point of OS was not reached in either group (p = 0.06).

The safety profile of the combination of IMBRUVICA and BR was the same as the safety profiles of both IMBRUVICA and BR.

“There is an urgent need to improve outcomes for older patients with MCL. Given the median progression-free survival of 6.7 years, the ibrutinib combination demonstrated the potential to be a first-line treatment in this population,”

said Michael L. Wang, M.D., Professor, Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center and principal study investigator.

Among all patients who were treated, neutropenia (IMBRUVICA plus BR: 47.1 percent; BR: 48.1 percent), pneumonia (IMBRUVICA plus BR: 20.1 percent; BR:14.2 percent), anaemia (IMBRUVICA® plus BR: 15.4 percent; BR: 8.8 percent), thrombocytopenia (IMBRUVICA plus BR: 12.7 percent; BR: 13.1 percent), rash (IMBR   Atrial fibrillation (AF) was reported by 13.9% of patients in the IMBRUVICA plus BR arm and by 6.5% of patients in the placebo arm. Hypertension was reported by 13.5% and 11.2%, respectively; major bleeding was reported by 5.8% and 4.2%; any bleeding was reported by 42.9 and 21.5 percent; and arthralgia was reported by 17.4% and 16.9%, respectively. 

“More than eight years since its first FDA approval, IMBRUVICA has treated over 250,000 patients globally, fundamentally changing the treatment paradigm for complex B-cell malignancies. The Phase 3 SHINE study reinforces our continued commitment to the development of IMBRUVICA to provide meaningful differences and change outcomes for patients with B-cell malignancies where high unmet medical needs still remain,”

said Craig Tendler, M.D., Vice President, Late Development and Global Medical Affairs, Janssen Research & Development, LLC.

IMBRUVICA is currently approved around the world to treat adults with mantle cell lymphoma (MCL) who have already been through at least one other treatment.

In the U.S., this indication has been approved based on the overall response rate (ORR). Continued approval for this use may depend on whether or not a confirmatory trial shows and describes clinical benefit (s).

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