ASCT Shows No OS Effects vs Maintenance Rituximab After BR or R-CHOP in MCL

According to an analysis of retrospective data from 4,216 patients with mantle cell lymphoma (MCL), autologous stem-cell transplant (ASCT) was underutilized in the community setting in the United States, showing the need for more treatments that can be delivered effectively in routine clinical practice.

Data showed there to be no significant association between ASCT and real-world time to next treatment (rwTTNT; hazard ratio [HR], 0.84; 95% CI, 0.68-1.03; P = .10) or overall survival ([OS]; HR, 0.86; 95% CI, 0.63-1.18; P = .4) among ASCT-eligible patients. For maintenance rituximab-eligible patients, maintenance rituximab after bendamustine plus rituximab (BR) vs BR alone correlated with a longer rwTTNT (HR, 1.96; 95% CI, 1.6- 2.38; P < .001) and OS (HR, 1.51; 95% CI, 1.19-1.92; P < .001). Further, the efficacy findings were consistent in the validation cohort.

Based on findings from this validation cohort, future clinical trials exploring regimens without ASCT consolidation in young patients are supported. Additionally, maintenance with rituximab should be considered for patients after first-line treatment with BR and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

“The efficacy outcomes in the Flatiron cohort appeared worse than those in other observational studies, particularly in patients age < 65 years with a median rwTTNT of 28.0 months…On the other hand, the efficacy outcomes seen with [first-line] BR[median rwTTNT of 34.4 months] and [first-line] R-CHOP [median rwTTNT of 16 months] were consistent with PFS reported in clinical trials,” wrote study authors in findings published in The Journal of Clinical Oncology.

For younger patients with MCL, high-dose cytarabine-based induction followed by ASCT was a common first-line treatment, while older patients typically receive several chemoimmunotherapy regimens. According to researchers, the usefulness of ASCT in younger patients and maintenance rituximab after treatment with BR were topics of ongoing controversy.

Using 2 independent sources of real-world evidence in both community and academic settings, investigators sought to assess treatment patterns and outcomes of first-line MCL treatments. Here, determining the role of ASCT in younger patients and maintenance of rituximab after induction with BR was highlighted.

Retrospective data from patients with MCL in the Flatiron Health electronic record-derived database who were diagnosed between 2011 and 2021 were used in the analysis. These patients were mostly from community oncology settings in the United States. Investigators evaluated treatment patterns and outcomes in these patients with first-line MCL, assessed the impact of ASCT in patients aged < 65 years, and looked at maintenance rituximab after BR or R-CHOP in 2 large independent real-world cohorts, the Flatiron and independent validation cohorts.

In the Flatiron cohort, 3,614 of 4,216 patients had records of MCL treatment and here, there were 2 target study populations: the MR-eligible cohort and ASCT-eligible cohort. The ASCT-eligible cohort included patients who had disease control after induction treatment, aligning with selection of patients for ASCT and maintenance rituximab in trials and routine practice.

The maintenance-rituximab cohort (n = 1,461) consisted of patients of any age who were alive and did not initiate second-line treatment within 8 months of starting first-line BR or 6 months of first-line R-CHOP. This cohort did not contain patients who received ASCT. Then in the ASCT-eligible cohort (n = 962) patients aged < 65 years who were alive and did not initiate subsequent treatment within 6 months of starting the first-line treatment were included. Sensitivity analyses were performed using cutoffs of 6, 8, or 10 months.

In the validation cohort (n = 1,168), response and progression data were available while data on the initiation of second-line treatment was not. Patients in the maintenance rituximab-eligible validation cohort (n = 298) were those of any age who were alive and did not have disease progression within 8 months of starting first-line BR or 6 months of first-line R-CHOP. The ASCT-eligible cohort for this group (n = 511) included patients who were aged < 65 years, were alive, and did not have disease progression within 6 months of starting first-line treatment.

The Flatiron cohort assessed patient characteristics as documented in the electronic health record, treatment patterns, rwTTNT, and OS. The validation cohort evaluated the primary end points of progression-free survival (PFS) and OS.

Among the 3,614 patients included in the Flatiron cohort, the median age of patients was 69.4 (range, 27.7-84.6) years, and 87% of patients were treated in a community oncology setting. Patients treated with BR were older than those treated with cytarabine-containing regimens or R-CHOP, with median ages of 73, 60, and 66 years, respectively.

For patients aged < 65 years (n = 1,265), cytarabine-containing regimens were most frequently used (30.5%). This was followed by BR (28.0%) and R-CHOP (22.1%).

A total of 23.5% of patients received ASCT, and 20.9% received maintenance rituximab. In patients aged < 65 years (n = 287), the most common induction regimens before ASCT were R-CHOP (21.3%), BR (19.2%), rituximab plus cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (18.1%), and dose-intensified rituximab plus cyclophosphamide, vincristine, doxorubicin, prednisone alternating with rituximab plus high-dose cytarabine (16.4%). For patients aged ≥ 65 years (n = 2,329), BR was used in 49.0%, R-CHOP in 15.2%, VR-CAP in 1.8%, and maintenance rituximab in 24.3%. Finally, in the overall cohort, 120 of 3,614 (3.3%) patients received both ASCT and maintenance rituximab.

Patients in the validation cohort of the trial were younger than those in the Flatiron cohort (median age 62 vs 69 years), and the use of ASCT in patients aged < 65 years was more frequent (47% vs 23.5%).

Overall, treatment with R-CHOP decreased from 32.9% in 2011 to 9.7% in 2020 while the use of BR increased from 19.7% in 2011 to 52.9% in 2020. Further, use of maintenance rituximab increased from 14.3% in 2011 to 27.2% in 2019 in patients aged < 65 years, and the use of cytarabine, ASCT, or maintenance rituximab in patients aged ≥ 65 years did not change notably over time.

Findings revealed that with a median follow-up of 45.5 months (range, 0.03-119.4), the overall median rwTTNT in the first-line MCL Flatiron cohort was 24.0 months (95% CI, 21.9- 26.2). Those aged < 65 years had better outcomes compared with patients aged ≥ 65 years. Here, the median rwTTNT was 28.0 months (95% CI, 24.4-34.5) vs 22.3 months (95% CI, 20.7-24.5).

The median rwTTNT of patients treated with BR and cytarabine-containing regimens were similar at 34.4 months (95% CI, 31.1-37.9) and 31.0 months (95% CI, 24.2-41.7), respectively. However, the median rwTTNT with R-CHOP was 16.0 months (95% CI, 13.2-19.0).

At 3 years, the OS rate was 68% (95% CI, 66-69) in the whole cohort compared with 68% (95% CI, 66-71) with BR, 74% (95% CI, 70-77) with R-CHOP, and 73% (95% CI, 68-77) with cytarabine-containing regimens. In the MR-eligible cohort of the Flatiron cohort, the median duration of induction therapy was 4.7 months regardless of maintenance rituximab use.

The median duration of maintenance rituximab was 19.9 months, and maintenance rituximab use following BR vs BR alone was associated with significantly longer rwTTNT (HR, 1.96; 95% CI, 1.61-2.38; P < .001). Additionally, the OS here was also longer (HR, 1.51; 95% CI, 1.19 to 1.92; P < .001).

For BR plus maintenance rituximab, the 3-year rwTTNT and OS rates were 74.0% (95% CI, 69-79) and 84.0% (95% CI, 80-88), respectively. This compared with 51.0% (95% CI, 46-56) and 74.0% (95% CI, 70-79) with BR alone.

In both the Flatiron and validation cohorts, significantly improved PFS and OS rates were observed with BR plus maintenance rituximab. In the validation cohort, 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, in patients treated with BR plus maintenance rituximab compared with 48.5% (95% CI, 30.5-64.3) and 73.2% (95% CI, 53.7-85.5) with BR alone.

Overall, maintenance rituximab after treatment with first-line R-CHOP led to improved outcomes vs R-CHOP alone in both the Flatiron and validation cohorts. The rwTTNT or PFS rates at 3 years were numerically higher with BR plus maintenance rituximab compared with R-CHOP plus maintenance rituximab. The 3-year OS rates were similar.

“Taken together, our findings from 2 large retrospective cohorts provide additional considerations for the design of future trials evaluating new treatment regimens in MCL,” concluded the study authors.

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. 2023;41(3):541-554. doi:10.1200/JCO.21.02698