Real-World Care Not Matching Recommendations From Clinical Trials in MCL

Discrepancies between real-world care and recommendations based on clinical trials were revealed in a study of adult patients with mantle cell lymphoma (MCL).

The retrospective analysis included patients (n = 4216) with a confirmed MCL diagnosis in the Flatiron Health de-identified database between January 2011 and January 2021 by the Flatiron Health database; 3614 had a record of frontline treatment for MCL. All the patients were 18 years or older and had at least 2 recorded clinic visits. Data originated from 280 cancer clinics representing 800 sites of care; most patients (86.6%) were treated in community oncology settings.

MCL is most commonly treated in younger patients (≤65) with chemoimmunotherapy with or without autologous stem cell transplantation (SCT), and in older patients (≥65) with bendamustine-rituximab (Rituxan; BR) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

“Our understanding of how clinical study findings are reflected in routine clinical practice is limited,” Peter Martin, MD, associate professor of medicine and chief of the Lymphoma Program at Weill Cornell Medicine, New York, said during a presentation of the data at the European Hematology Association 2021 Virtual Congress.. “These data highlight the need to develop treatment regimens that can be delivered effectively in routine and community practices, and treatments may not need to be centered around SCT intent in young patients.”

Patient characteristics, treatment patterns, real-world time-to-next treatment (rwTTNT), and real-world overall survival (rwOS) were evaluated. rwTTNT was defined as the time from start of first-line treatment to subsequent treatment or death, whichever came first; rwOS as time from start of first-line treatment to death.

“This was a retrospective analysis,” Martin said. “There were missing data in the baseline characteristics. The tumor response and disease progression data were not available to evaluate overall response rate or progression-free survival. And the intention for choosing treatments (eg, transplantation or maintenance) was not captured in the database.”

Still, significant data were revealed: in patients under 65 years, only 30.5% received a cytarabine-containing regimen; 23.3% received SCT. In patients over 65 years, about 65% received BR or R-CHOP. Median rwTTNT was 28 months in patients under 65 and 22.3 months in patients 65 years or older, which, according to Martin, “appears worse than what has been reported with standard therapies in this population. Older age and high-risk disease features were predictive of worse outcome in the real world, while [rituximab] maintenance appeared to be associated with better outcome. Among the SCT-eligible patients, there was no clear rwTTNT or rwOS benefit associated with receipt.”

Median follow-up in patients with documented first-line MCL treatment was 45.5 months (range, 0.033-119.4) and median rwTTNT was 24 months (28 months in patients <65 years and 22.3 months in patients ≥65 years). At 36 months, the rwTTNT was 41% (95% CI, 39%-43%) for all patients, 46% (95% CI, 43%-49%) for patients <65 years, and 38% (95% CI, 36%-41%) for patients ≥65 years. The 36-month rwOS rate was 68% (95% CI, 66%-69%) in all patients, 78% (95% CI, 75%-81%) in younger patients, and 62% (95% CI, 60%-65%) in older patients.

The 36-month rwTTNT rate was comparable for patients under 65 years treated with SCT (65%; 95% CI, 59%-71%) compared with those did not receive SCT (59%; 95% CI, 55%-64%; log-rank P = .082). At 3 years, the rwOS rate was 87% (95% CI, 83%-92%) in younger patients who received SCT and 84% (95% CI, 81%-88%) in those who did not receive SCT (log-rank P = .387). For patients 65 years or older who were not treated with SCT, the 36-month rate of rwTTNT was 37% (95% CI, 35%-40%).

Among eligible patients with a record of treatment, 2340 patients (64.7%) were 65 years or older and 1274 (35.3%) were under age 65. Of the younger group, 971 patients were SCT eligible and 291 received SCT. A total of 23.1% received rituximab maintenance therapy.

Overall, the median age for the study was 69.4 years (range, 27.7-84.6), with 64.7% of patients over age 65, 71.5% male, and 86.6% treated in a community oncology setting. Patients treated with cytarabine-containing regimens (n = 514) and SCT (n = 291) were younger (median, 60.1 and 59.6 years, respectively) than those treated with R-CHOP (n = 636; median age, 66.3) or BR (n = 1502; median age, 72.7) and were less likely to be treated in the community. Patients treated with cytarabine-based regimens were also more likely to have blastoid/pleomorphic morphology (20%) than the overall patient group (10%) but had a low-risk MCL International Prognostic Index (MIPI) score. Those treated with SCT were more likely to have a lower MIPI score than the overall population as well as those treated with BR or R-CHOP.

Reference

Martin P, Wang M, Kumar A, et al. Real-world treatment patterns and outcomes of 4216 previously untreated mantle cell lymphoma patients in US routine clinical practice. Presented at: European Hematology Association 2021 Congress; June 9-12, 2021; Virtual. Abstract EP798.