Rituximab Maintenance Therapy Alone or Combined With a BTK Inhibitor

A prospective randomized trial included 299 patients with MCL who underwent chemoimmunotherapy and autologous stem cell transplant (SCT) consolidation. Patients were then randomly assigned to receive either 3 years of rituximab maintenance therapy or observation.[1]

A prospective randomized trial included 299 patients with MCL who underwent chemoimmunotherapy and autologous stem cell transplant (SCT) consolidation. Patients were then randomly assigned to receive either 3 years of rituximab maintenance therapy or observation.[1]

With a median follow-up of 50.2 months after autologous SCT, the overall survival (OS) rate was 89% (95% confidence interval [CI], 81%–94%) in the rituximab group and 80% (95% CI 72%–88%) in the observation group (hazard ratio [HR], 0.50; 95% CI, 0.26–0.99; P = .04).[1][Level of evidence A1]

A prospective randomized trial included 299 patients with MCL who underwent chemoimmunotherapy and autologous stem cell transplant (SCT) consolidation. Patients were then randomly assigned to receive either 3 years of rituximab maintenance therapy or observation.[1]

The 4-year event-free survival rate was 79% (95% CI, 70%–86%) in the rituximab group and 61% (95% CI, 51%–70%) in the observation group (P = .001).[1]

A prospective randomized trial included 299 patients with MCL who underwent chemoimmunotherapy and autologous stem cell transplant (SCT) consolidation. Patients were then randomly assigned to receive either 3 years of rituximab maintenance therapy or observation.[1]

The 4-year progression-free survival (PFS) rate was 83% (95% CI, 73%–88%) in the rituximab group and 64% (95% CI, 55%–73%) in the observation group (P < .001).[1]

In a prospective trial of 299 patients with untreated MCL, 257 responders received four courses of R-DHAP (rituximab, dexamethasone, cytarabine, and cisplatin) and autologous SCT. These patients were then randomly assigned to receive either rituximab maintenance therapy for 3 years or no maintenance therapy.[2]

In a prospective trial of 299 patients with untreated MCL, 257 responders received four courses of R-DHAP (rituximab, dexamethasone, cytarabine, and cisplatin) and autologous SCT. These patients were then randomly assigned to receive either rituximab maintenance therapy for 3 years or no maintenance therapy.[2]

The 7-year PFS rate was significantly higher for the rituximab maintenance group at 78.5 % (95% CI, 69.9%–85.0%) versus 47.4% (95% CI, 39.9%–56.3%) for the group that did not receive maintenance therapy (HR, 0.36; 95% CI, 0.23–0.56; P < .0001).[2][Level of evidence B1]

In a prospective trial of 299 patients with untreated MCL, 257 responders received four courses of R-DHAP (rituximab, dexamethasone, cytarabine, and cisplatin) and autologous SCT. These patients were then randomly assigned to receive either rituximab maintenance therapy for 3 years or no maintenance therapy.[2]

After randomization, with a median follow-up of 7.5 years, the 7-year OS rate in the rituximab maintenance group was not significantly better than in the no-maintenance group (83.2% [95% CI, 74.7%–89.0%] vs. 72.2% [95% CI, 62.9%–79.5%]; HR, 0.63; 95% CI, 0.37–1.08).

In a prospective randomized trial, 500 patients aged 60 years or older and not transplant-eligible received induction therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-FC (rituximab, fludarabine, cyclophosphamide) for six to eight cycles. Responders were randomly assigned to receive either rituximab or interferon alfa maintenance therapy until disease relapse.[3]

In a prospective randomized trial, 500 patients aged 60 years or older and not transplant-eligible received induction therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-FC (rituximab, fludarabine, cyclophosphamide) for six to eight cycles. Responders were randomly assigned to receive either rituximab or interferon alfa maintenance therapy until disease relapse.[3]

With a median follow-up of 8.0 years for the 316 responding patients, the median OS was 9.8 years in the rituximab maintenance group and 7.1 years in the interferon alfa maintenance group (P = .0054).[3][Level of evidence A1]

As previously described, the TRIANGLE trial (NCT02858258) was a prospective randomized trial that included 870 patients aged 65 years or younger with previously untreated MCL who were transplant-eligible.[4,5] Patients received one of three induction regimens with chemoimmunotherapy (R-CHOP/R-DHAP), with or without ibrutinib and with or without autologous SCT consolidation in the ibrutinib arms. All patients were recommended to have maintenance therapy with at least rituximab or with both rituximab and ibrutinib in the ibrutinib induction therapy arms.[6] Not all patients could tolerate or receive maintenance therapy, and some deferred the recommended maintenance therapy (33%–41% of patients in each group).

As previously described, the TRIANGLE trial (NCT02858258) was a prospective randomized trial that included 870 patients aged 65 years or younger with previously untreated MCL who were transplant-eligible.[4,5] Patients received one of three induction regimens with chemoimmunotherapy (R-CHOP/R-DHAP), with or without ibrutinib and with or without autologous SCT consolidation in the ibrutinib arms. All patients were recommended to have maintenance therapy with at least rituximab or with both rituximab and ibrutinib in the ibrutinib induction therapy arms.[6] Not all patients could tolerate or receive maintenance therapy, and some deferred the recommended maintenance therapy (33%–41% of patients in each group).

In a retrospective analysis with a median follow-up of 4.0 years, the 4-year PFS rate was 10% to 29% higher for patients who received rituximab maintenance (P ranged from .016 to < .001).[6][Level of evidence C3]

A retrospective analysis of 1,265 patients aged 65 years and younger evaluated rituximab maintenance therapy after bendamustine and rituximab induction.[7]

A retrospective analysis of 1,265 patients aged 65 years and younger evaluated rituximab maintenance therapy after bendamustine and rituximab induction.[7]

A benefit was seen for rituximab maintenance therapy in time-to-next treatment (HR, 1.96; 95% CI, 1.61–2.38; P < .001) and OS (HR, 1.51; 95% CI, 1.19–1.92; P < .001).[7][Level of evidence C3]

In a prospective randomized trial, 319 patients with follicular lymphoma or MCL received R-FCM (rituximab, fludarabine, cyclophosphamide, and mitoxantrone) or FCM (a subsequent analysis confirmed the superiority of R-FCM and all patients received that induction). The 267 patients with disease response were randomly assigned to either rituximab maintenance therapy or observation. Most patients had follicular lymphoma, but 47 patients with disease response had MCL.[8]

In a prospective randomized trial, 319 patients with follicular lymphoma or MCL received R-FCM (rituximab, fludarabine, cyclophosphamide, and mitoxantrone) or FCM (a subsequent analysis confirmed the superiority of R-FCM and all patients received that induction). The 267 patients with disease response were randomly assigned to either rituximab maintenance therapy or observation. Most patients had follicular lymphoma, but 47 patients with disease response had MCL.[8]

With a median follow-up of 26 months, the 2-year PFS rate was 45% in the rituximab maintenance group and 9% in the observation group (P = .049).[8][Level of evidence B1]