Study Shows Real-World Benefit of Rituximab Maintenance After Frontline BR in Mantle Cell Lymphoma

Rituximab (Rituxan) maintenance therapy following frontline bendamustine plus rituximab (BR) improved event-free survival (EFS), EFS following second-line therapy (EFS2), and overall survival (OS) vs no maintenance therapy in patients with mantle cell lymphoma (MCL), according to findings from a large, observational cohort study presented at the 2024 ASCO Annual Meeting.¹

The median EFS was 3.9 years with rituximab maintenance (n = 318) vs 2.5 years with no maintenance (n = 295), and the respective 5-year EFS rates in these groups were 46% and 28% (sex- and simplified Mantle Cell Lymphoma International Prognostic Index [sMIPI]–adjusted HR, 0.59; 95% CI, 0.48-0.73; log-rank P < .0001).

When EFS outcomes were stratified by response to frontline BR, patients who achieved a complete response (CR) had a median EFS of 5.1 years in the rituximab maintenance group vs 2.6 years in the group with no maintenance (adjusted HR, 0.56; 95% CI, 0.44-0.71; log-rank P < .0001). The 5-year EFS rates in these respective groups were 50% and 31%. Patients who achieved a partial response (PR) had a median EFS of 1.7 years in the rituximab maintenance group vs 1.0 years in the group with no maintenance (adjusted HR, 0.82; 95% CI, 0.49-1.37; log-rank P = .037). The 5-year EFS rates in these respective groups were 19% and 10%.

“[The EFS, EFS2, and OS] benefits of rituximab maintenance were clear in patients who achieved CR to first-line BR, but uncertain in those who achieved a PR, only due to a small sample size in this subset,” lead study author Yucai Wang, MD, PhD, stated in the presentation. Wang is an assistant professor of medicine and oncology and a consultant in the Division of Hematology at the Mayo Clinic Comprehensive Cancer Center in Rochester, Minnesota.

Previously, the phase 2 MAINTAIN trial (NCT00877214) demonstrated that first-line BR followed by rituximab maintenance therapy did not lead to statistically significant improvement in progression-free survival (PFS) or OS in patients with MCL. At a median follow-up of 58.6 months, the median PFS was 72.3 months with rituximab maintenance vs 54.7 months with observation (HR, 0.71; 95% CI, 0.41-1.23; P = .2267).2 Furthermore, the median OS was not yet reached (NR) with either rituximab maintenance or observation (HR, 1.51; 95% CI, 0.70-3.25; P = .2974).

However, Wang noted that retrospective studies have indicated the potential benefits of using rituximab maintenance therapy after frontline BR.¹ For instance, real-world data collected from the Flatiron community practice database between 2011 and 2021 showed that patients who received frontline BR had a median OS of 89.5 months (95% CI, 80.0-108.6) with the addition of rituximab maintenance (n = 427) vs 78.1 months (95% CI, 62.9-93.5) with BR alone (HR, 1.51; 95% CI, 1.19-1.92; log-rank test P < .001).³

Based on these findings, investigators examined the potential benefit of rituximab maintenance following frontline BR in a large, observational cohort study.¹

The study included patients at least 18 years of age with a confirmed MCL diagnosis with t(11;14)(q13;q32) translocation and/or CD1 expression. Patients needed to have received frontline BR, with or without rituximab maintenance therapy.

Patients were excluded if they had received frontline treatment in the phase 3 ECHO (NCT02972840) or SHINE (NCT01776840) trials; received a BTK inhibitor in combination with BR; received another active MCL therapy in combination with BR, including venetoclax (Venclexta), bortezomib (Velcade), or cytarabine (pre-phase steroid use was allowed); underwent autologous stem cell transplantation consolidation therapy after BR; or received maintenance therapy with an agent other than rituximab.

A total of 796 patients who had received frontline BR were screened, 183 of whom were excluded, leaving 613 eligible for the rituximab maintenance landmark analysis.

In the rituximab maintenance group, patients had a median age of 69 years (range, 32-91; interquartile range [IQR], 64-74), and most were male (77.7%). In total, 23.2%, 38.0%, and 38.8% of patients, respectively, had an sMIPI score of 0 to 3 (low), 4 to 5 (intermediate), or 6 to 11 (high).

In the group of patients who did not receive rituximab maintenance, patients had a median age of 71 years (range, 34-90; IQR, 64-76), and most were male (68.5%). In total, 19.7%, 43.7%, and 36.6% of patients had low, intermediate, or high sMIPI scores, respectively.

Additional data showed the median EFS2 was 7.4 years with rituximab maintenance vs 4.0 years with no maintenance, and the respective 5-year EFS2 rates in these groups were 59% and 42% (adjusted HR, 0.63; 95% CI, 0.50-0.81; log-rank P = .00032).

When EFS2 outcomes were stratified by response to frontline BR, patients who achieved a CR had a median EFS2 of 8.0 years in the rituximab maintenance group vs 4.6 years in the group with no maintenance (adjusted HR, 0.62; 95% CI, 0.48-0.81; log-rank P = .00054). The 5-year EFS2 rates in these respective groups were 62% and 46%. Patients who achieved a PR had a median EFS2 of 4.1 years in the rituximab maintenance group vs 2.5 years in the group with no maintenance (adjusted HR, 0.69; 95% CI, 0.39-1.22; log-rank P = .021). The 5-year EFS2 rates in these respective groups were 37% and 19%.

The median OS was 11.3 years with rituximab maintenance vs 6.2 years with no maintenance, and the respective 5-year OS rates in these groups were 71% and 57% (adjusted HR, 0.57; 95% CI, 0.44-0.75; log-rank P < .0001).

Patients who achieved a CR following BR had a median OS of 11.3 years in the rituximab maintenance group vs 6.3 years in the group with no maintenance (adjusted HR, 0.59; 95% CI, 0.44-0.79; log-rank P = .00038). The 5-year OS rates in these respective groups were 72% and 59%. Patients who achieved a PR had a median OS of 7.3 years in the rituximab maintenance group vs 3.9 years in the group with no maintenance (adjusted HR, 0.48; 95% CI, 0.24-0.98; log-rank P = .067). The 5-year EFS rates in these respective groups were 64% and 46%.

“Within the constraints of observational data, our results provide support for rituximab maintenance therapy after first-line BR in patients with MCL,” Wang concluded.

Disclosures: Dr Wang reports an immediate family member employed by Merck; an immediate family member’s stock or other ownership interests with Merck; honoraria paid to his institution from Kite; institutional consulting or advisory roles with AstraZeneca, BeiGene, Genmab, Incyte, Innocare, Janssen, Kite, Lilly, Loxo, and TG Therapeutics; and research funding paid to his institution from Genentech, Genmab, Incyte, Innocare, Loxo, MorphoSys, and Novartis.

References

1. Wang Y, Larson MC, Kumar A, et al. Benefit of rituximab maintenance after first-line bendamustine-rituximab in mantle cell lymphoma. J Clin Oncol. 2024;42(suppl 16):7006. doi:10.1200/JCO.2024.42.16_suppl.7006
2. Rummel MJ, Knauf W, Goerner M, et al. Two years rituximab maintenance vs. observation after first-line treatment with bendamustine plus rituximab (B-R) in patients with mantle cell lymphoma: first results of a prospective, randomized, multicenter phase II study (a subgroup study of the StiL NHL7-2008 MAINTAIN trial). J Clin Oncol. 2016(34):7503. doi:10.1200/JCO.2016.34.15_suppl.7503
3. Martin P, Cohen JB, Wang M, et al. Treatment outcomes and roles of transplantation and maintenance rituximab in patients with previously untreated mantle cell lymphoma: results from large real-world cohorts. J Clin Oncol. 2023;41(3). doi:10.1200/JCO.21.2698