Treatment for Patients Who Have Received a Prior BTK Inhibitor

The reversible, noncovalent BTK inhibitor pirtobrutinib was evaluated in a phase I/II trial of 164 patients with relapsed/refractory MCL.[10]The FDA approved pirtobrutinib for patients who received two prior lines of therapy, including a covalent BTK inhibitor.

The reversible, noncovalent BTK inhibitor pirtobrutinib was evaluated in a phase I/II trial of 164 patients with relapsed/refractory MCL.[10]The FDA approved pirtobrutinib for patients who received two prior lines of therapy, including a covalent BTK inhibitor.

With a median follow-up of 12 months, among the 90 patients previously treated with covalent BTK inhibitors (ibrutinib, acalabrutinib, or zanubrutinib), the overall response rate was 57.8% (95% CI, 46.9%–68.1%), including a complete response rate of 20.0%.[10][Level of evidence C3]

The reversible, noncovalent BTK inhibitor pirtobrutinib was evaluated in a phase I/II trial of 164 patients with relapsed/refractory MCL.[10]The FDA approved pirtobrutinib for patients who received two prior lines of therapy, including a covalent BTK inhibitor.

The median duration of response was 2.6 months (95% CI, 7.5–NR).[10][Level of evidence C2]

The reversible, noncovalent BTK inhibitor pirtobrutinib was evaluated in a phase I/II trial of 164 patients with relapsed/refractory MCL.[10]The FDA approved pirtobrutinib for patients who received two prior lines of therapy, including a covalent BTK inhibitor.

Only 3% of patients discontinued therapy because of side effects, which included atrial fibrillation in 1.2% of patients, grade 3 or higher bleeding in 3.7%, dyspnea in 16.5%, diarrhea in 21.3%, and fatigue in 29.9%.

The combination of lenalidomide plus rituximab has been studied in several phase II trials, with an overall response rate of approximately 50% in patients with relapsed MCL.[11-13][Level of evidence C3]

A prospective phase II trial (ZUMA-2 [NCT02601313]) included 68 patients with relapsed or refractory MCL whose disease failed to respond to BTK inhibitors. Patients received CAR T-cell therapy with brexucabtagene autoleucel, which targets CD19.[14]

A prospective phase II trial (ZUMA-2 [NCT02601313]) included 68 patients with relapsed or refractory MCL whose disease failed to respond to BTK inhibitors. Patients received CAR T-cell therapy with brexucabtagene autoleucel, which targets CD19.[14]

With a median follow-up of 36 months, the objective response rate was 91% (95% CI, 82%–97%), the complete response rate was 68% (95% CI, 55%–78%), the median PFS was 25.8 months (95% CI, 10–48), and the OS was 46.6 months (95% CI, 24.9–NE).[14][Level of evidence C3]

A prospective phase II trial (ZUMA-2 [NCT02601313]) included 68 patients with relapsed or refractory MCL whose disease failed to respond to BTK inhibitors. Patients received CAR T-cell therapy with brexucabtagene autoleucel, which targets CD19.[14]

Grade 3 or higher cytokine release syndrome occurred in 15% of patients, and neurological events occurred in 31% of patients.

A prospective phase II trial (ZUMA-2 [NCT02601313]) included 68 patients with relapsed or refractory MCL whose disease failed to respond to BTK inhibitors. Patients received CAR T-cell therapy with brexucabtagene autoleucel, which targets CD19.[14]

A retrospective evaluation at 16 institutions included 168 patients who received brexucabtagene autoleucel as part of the U.S. Lymphoma CAR-T Consortium. The study showed similar response rates and PFS as the ZUMA-2 trial.[15][Level of evidence C3]

Patients with relapsed or refractory MCL who had received a median of three prior lines of therapy were enrolled in a phase I/II trial of lisocabtagene maraleucel, an anti-CD19 CAR T-cell therapy.[16]

Patients with relapsed or refractory MCL who had received a median of three prior lines of therapy were enrolled in a phase I/II trial of lisocabtagene maraleucel, an anti-CD19 CAR T-cell therapy.[16]

With a median follow-up of 16.1 months, the objective response rate was 83.1% (95% CI, 73.3%–90.5%), and the complete response rate was 72.3% (95% CI, 61.4%–81.6%). The median duration of response was 15.7 months (95% CI, 6.2–24.0).[16][Level of evidence C3]

Patients with relapsed or refractory MCL who had received a median of three prior lines of therapy were enrolled in a phase I/II trial of lisocabtagene maraleucel, an anti-CD19 CAR T-cell therapy.[16]

Grade 3 or higher cytokine release syndrome occurred in 1% of patients.

Patients with relapsed or refractory MCL received the CD20 × CD3 bispecific antibody glofitamab in a phase I/II trial.[17]

Patients with relapsed or refractory MCL received the CD20 × CD3 bispecific antibody glofitamab in a phase I/II trial.[17]

With a median follow-up of 19.6 months, 60 patients were evaluable. The overall response rate was 85.0% (95% CI, 73.4%–92.9%), and the complete response rate was 78.3% (95% CI, 65.8%–87.9%).[17][Level of evidence C3]

Patients with relapsed or refractory MCL received the CD20 × CD3 bispecific antibody glofitamab in a phase I/II trial.[17]

The median duration of complete response was 15.4 months (95% CI, 12.7–NE), and the 1-year duration of complete response was 71.0% (95% CI, 56.8%–85.2%).[17][Level of evidence C3]

Patients with relapsed or refractory MCL received the CD20 × CD3 bispecific antibody glofitamab in a phase I/II trial.[17]

Grade 3 or higher cytokine release syndrome occurred in 25% of patients. No grade 3 or higher neurological symptoms were reported.