Real-World Data Highlight Underutilization of High-Dose Cytarabine/Transplant, Benefits of Maintenance Rituximab in MCL

Autologous stem cell transplant had no effect on real-world time to next treatment and overall survival compared with maintenance rituximab following induction with bendamustine and rituximab or R-CHOP, for patients with mantle cell lymphoma according to findings from a retrospective study.

Autologous stem cell transplant (ASCT) had no effect on real-world time to next treatment (TTNT) and overall survival (OS) compared with maintenance rituximab (Rituxan) following induction with bendamustine and rituximab (Rituxan; BR) or R-CHOP, for patients with mantle cell lymphoma (MCL), according to findings from a retrospective study published in the Journal of Clinical Oncology. Maintenance rituximab prolonged both end points compared with BR alone in this population.

“In this large cohort of patients treated primarily in the US community setting, only 1 in 4 young patients received cytarabine or ASCT consolidation, suggesting the need to develop treatments that can be delivered effectively in routine clinical practice,” the study authors wrote. “Together with the validation cohort, data support future clinical trials exploring regimens without ASCT consolidation in young patients, whereas maintenance rituximab should be considered for patients after first-line BR and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP].”

Standard frontline treatment for younger patients with MCL includes high-dose cytarabine-containing chemoimmunotherapy followed by ASCT and maintenance rituximab. Patients aged 65 years or older who cannot tolerate intensive treatment often receive chemoimmunotherapy regimens such as BR, R-CHOP, and bortezomib (Velcade) plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP). However, uncertainty remains regarding the role of transplant in younger patients and maintenance rituximab after BR.

As such, investigators compiled retrospective data from the Flatiron Health electronic record-derived deidentified database of 4216 patients with MCL diagnosed from 2011 to 2021 to evaluate treatment patterns and outcomes. To be eligible for inclusion, patients had to be at least 18 years of age and have a confirmed diagnosis of MCL and at least 2 documented clinic visits (n = 3614).

The cohort of patients who received maintenance rituximab (n = 1461) included those of any age so long as they did not start second-line treatment within 8 months of starting first-line BR or 6 months of frontline R-CHOP; patients who received ASCT were excluded. The ASCT-eligible cohort (n = 962) included patients younger than 65 years who were alive and did not receive subsequent treatment within 6 months of starting frontline therapy.

The efficacy findings with ASCT and maintenance rituximab were validated in an independent cohort of 1168 patients from 12 academic centers. Here, the validation cohort of patients who received maintenance rituximab (n = 258) included those of any age who were alive and did not have disease progression within 8 months of starting frontline BR or 6 months of frontline R-CHOP. The ASCT-eligible validation cohort (n = 511) included patients younger than 65 years who were alive and did not have disease progression within 6 months of starting frontline therapy.

Among patients in the Flatiron cohort, the median age was 69.4 years (range, 27.7-84.6); 87% of patients received treatment in a community setting. BR-treated patients were older than those treated with cytarabine-containing regimens or R-CHOP.

BR was the most commonly used regimen among patients with documented frontline treatment. Among 1265 patients younger than 65 years, 30.5% received cytarabine-based induction, followed by BR (28.0%) and R-CHOP (22.1%); 23.5% of patients received ASCT and 20.9% received maintenance rituximab. In patients 65 years of age or older (n = 2329), 49.0% received BR, 15.2% received R-CHOP, 1.8% received VR-CAP, and 24.3% received maintenance rituximab.

In the overall cohort, only 3.3% (n = 120/3614) received ASCT and maintenance rituximab.

Notably, R-CHOP administration decreased from 32.9% in 2011 to 9.7% in 2020. In contrast, use of BR increased from 19.7% to 52.9% over the same period. The use of maintenance rituximab increased from 14.3% in 2011 to 27.2% in 2019 in patients younger than 65 years. The use of cytarabine, ASCT, or maintenance rituximab remained unchanged over time in patients aged 65 years or older.

Additionally, patients in the validation cohort were younger than those in the Flatiron cohort, and the use of ASCT in patients under the age of 65 years was twice as common (47.0% vs 23.5%).

Key findings from the analysis showed no significant association between ASCT and real-world TTNT (HR, 0.84; 95% CI, 0.68-1.03; P = .10) or OS (HR, 0.86; 95% CI, 0.63-1.18; P = .40) among ASCT-eligible patients. The 3-year real-world TTNT and OS rates were similar between patients who received ASCT (TTNT, 65%; 95% CI, 59%-71%; OS, 88%; 95% CI, 83%-92%) and those who did not (TTNT, 59%; 95% CI, 55%-64%; OS, 84%; 95% CI, 81%-88%).

In the validation cohort (n = 511), the 3-year progression-free survival (PFS) rate for patients who received ASCT (n = 328) was 69.6% (95% CI, 63.6%-74.8%) vs 69.0% (95% CI, 61.2%-75.6%) for patients who did not receive ASCT (n = 183). The 3-year OS rates were also comparable regardless of ASCT status.

Among patients eligible for maintenance rituximab, inclusion after BR was associated with a longer real-world TTNT (HR, 1.96; 95% CI, 1.61-2.38; P <.001) and OS (HR, 1.51; 95% CI, 1.19-1.92; P < .001) vs BR alone.

The 3-year real-world TTNT and OS rates for BR plus maintenance rituximab were 74.0% (95% CI, 69%-79%) and 84.0% (95% CI, 80%-88%), respectively, vs 51.0% (95% CI, 46%-56%) and 74.0% (95% CI, 70%-79%) with BR alone. Multivariate analysis in this cohort suggested that omission of maintenance rituximab, age 65 years or older, lactate dehydrogenase/upper limit of normal of at least 1, bulky disease, and blastoid/pleomorphic morphology were associated with significantly shorter real-world TTNT and OS.

Maintenance rituximab–eligible patients in the validation cohort (n = 258) also experienced improved PFS and OS with the addition of the CD20 antibody as maintenance therapy following induction with BR. The 3-year PFS and OS rates were 74.2% (95% CI, 61.6%-83.2%) and 91.9% (95% CI, 81.6%-96.5%), respectively, vs 48.5% (95% CI, 30.5%-64.3%) and 73.2% (95% CI, 53.7%-85.5%) with BR alone.

“Taken together, our findings from two large retrospective cohorts provide additional considerations for the design of future trials evaluating new treatment regimens in MCL,” the authors concluded.

Reference

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. 2022;41(supp 3):541-554. doi:10.1200/JCO.21.02698

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