BTK inhibitors With or Without Other Drugs

A prospective trial, published in abstract form, included 397 patients aged 60 years and older with previously untreated MCL. Patients were randomly assigned to receive either ibrutinib plus rituximab or BR.[12]

A prospective trial, published in abstract form, included 397 patients aged 60 years and older with previously untreated MCL. Patients were randomly assigned to receive either ibrutinib plus rituximab or BR.[12]

With a median follow-up of 47.9 months, the PFS rate was 65.3% for patients who received ibrutinib plus rituximab and 42.4% for patients who received BR (HR, 0.69; 95% CI, 0.52–0.90; P = .003).[12][Level of evidence B1]

A prospective randomized trial (SHINE [NCT01776840]) included 523 patients aged 65 years and older with previously untreated MCL. Patients were randomly assigned to receive either ibrutinib plus BR or placebo plus BR. The primary end point was PFS.[13]

A prospective randomized trial (SHINE [NCT01776840]) included 523 patients aged 65 years and older with previously untreated MCL. Patients were randomly assigned to receive either ibrutinib plus BR or placebo plus BR. The primary end point was PFS.[13]

With a median follow-up of 84.7 months, the median PFS was 80.6 months for patients who received ibrutinib plus BR and 52.9 months for patients who received placebo plus BR (HR, 0.75; 95% CI, 0.59–0.96; P = .01). There was no difference in the 7-year OS rate (55.0% vs. 56.8%; HR, 1.07; 95% CI, 0.81–1.40).[13][Level of evidence B1]

A prospective randomized trial (SHINE [NCT01776840]) included 523 patients aged 65 years and older with previously untreated MCL. Patients were randomly assigned to receive either ibrutinib plus BR or placebo plus BR. The primary end point was PFS.[13]

The magnitude of benefit for PFS results contrasted with the lower 7-year OS may cast doubt on the long-term safety of the ibrutinib plus BR combination. Infectious deaths in the combination group contributed to the lack of survival advantage.

A prospective randomized trial (SHINE [NCT01776840]) included 523 patients aged 65 years and older with previously untreated MCL. Patients were randomly assigned to receive either ibrutinib plus BR or placebo plus BR. The primary end point was PFS.[13]

Further trials are required to determine if ibrutinib alone can achieve the same results without adding BR, potentially avoiding the increased toxicities and infectious deaths from including bendamustine.

In a prospective randomized trial, 280 patients with relapsed or refractory MCL received either ibrutinib or temsirolimus.[14]

In a prospective randomized trial, 280 patients with relapsed or refractory MCL received either ibrutinib or temsirolimus.[14]

With a median follow-up of 15 months, the median PFS was 14.6 months in the ibrutinib group and 6.2 months in the temsirolimus group (HR, 0.43; 95% CI, 0.32–0.58; P < .0001).[14][Level of evidence B1]

In a phase II trial of previously untreated patients older than 64 years with MCL, 50 patients received ibrutinib plus rituximab.[15]

In a phase II trial of previously untreated patients older than 64 years with MCL, 50 patients received ibrutinib plus rituximab.[15]

With a median follow-up of 45 months, the overall response rate was 96%, the complete response rate was 71%, the 3-year PFS rate was 87%, and the 3-year OS rate was 94%.[15][Level of evidence C3]

In a phase II trial of 131 previously untreated patients with MCL aged 65 years or younger, 1 year of ibrutinib plus 4 weeks of rituximab resulted in a complete response rate of 89% prior to any chemotherapy consolidation.[16][Level of evidence C3]

A phase II trial using ibrutinib plus rituximab included asymptomatic patients with previously untreated MCL.[17]

A phase II trial using ibrutinib plus rituximab included asymptomatic patients with previously untreated MCL.[17]

The complete response rate was 87%.[17][Level of evidence C3]

Ibrutinib was combined with another active agent, venetoclax, in a phase II study of 23 patients with relapsed or refractory MCL.[18]

Ibrutinib was combined with another active agent, venetoclax, in a phase II study of 23 patients with relapsed or refractory MCL.[18]

With a median follow-up of 7 years 4 months, the 7-year PFS rate was 30% (95% CI, 14%–49%), and the 7-year OS rate was 43% (95% CI, 23%–26%).[18][Level of evidence C3]

A randomized prospective trial (SYMPATICO [NCT03112174]) included 267 patients with relapsed or refractory MCL. The trial compared (1) ibrutinib plus venetoclax for 2 years followed by ibrutinib until disease progression versus (2) ibrutinib plus placebo followed by ibrutinib.[19]

A randomized prospective trial (SYMPATICO [NCT03112174]) included 267 patients with relapsed or refractory MCL. The trial compared (1) ibrutinib plus venetoclax for 2 years followed by ibrutinib until disease progression versus (2) ibrutinib plus placebo followed by ibrutinib.[19]

With a median follow-up of 51.2 months (interquartile range, 48.2–55.3), the median PFS was 31.9 months (95% CI, 22.8–47.0) in the ibrutinib-venetoclax group and 22.1 months (16.5–29.5) in the ibrutinib-placebo group (HR, 0.65; 95% CI, 0.47–0.88; P = .0052).[19]

Acalabrutinib was evaluated in a phase II study of 124 patients with relapsed or refractory MCL.[20]

Acalabrutinib was evaluated in a phase II study of 124 patients with relapsed or refractory MCL.[20]

There was an 81% overall response rate, 40% complete response rate, and 67% 1-year PFS rate.[20][Level of evidence C3]

Zanubrutinib was evaluated in a phase II study of 86 patients with relapsed or refractory MCL.[21]

Zanubrutinib was evaluated in a phase II study of 86 patients with relapsed or refractory MCL.[21]

After a median follow-up of 35.3 months, the overall response rate was 84%, the complete response rate was 78%, and the median PFS was 33.0 months.[21][Level of evidence C3]