Yale University School of Medicine, New Haven, CT
Mengyang Di , Jessica B. Long , Shalin Kothari , Tarsheen Kaur Sethi , Amer Methqal Zeidan , Nikolai Alexandrovich Podoltsev , Rory Shallis , Rong Wang , Xiaomei Ma , Scott F. Huntington
Background: In the clinical trial setting, rituximab maintenance (RM) improved survival of older adults with mantle cell lymphoma (MCL) compared to maintenance interferon following RCHOP. However, given the considerable shift away from the use of RCHOP for MCL, real-world effectiveness of RM is now uncertain for MCL in older adults. We used SEER-Medicare, a large population-based data set, to evaluate MCL treatment patterns and assess effectiveness of RM following standard chemoimmunotherapy in older patients. Methods: We selected adults ≥66 years old, diagnosed with MCL 2007-2017, with continuous Medicare A/B/D coverage, who received MCL therapy. We captured 1st and 2nd line regimens, defining RM as rituximab (R) given as a single agent after R-based multi-agent induction regimen, with treatment gap ≤200 days (d) prior, for ≥2 consecutive doses and lasting ≥ 28d. We examined the benefits of RM in patients who received bendamustine-R (BR) or RCHOP as 1st line with no consolidative stem cell transplant (SCT). We limited our control group to those who survived ≥ 200d (if no 2nd line given) or had a gap ≥ 200d between completion of induction and initiation of 2nd line treatment to reduce potential immortal time bias. We used propensity score matching (PSM) based on age, sex, race, marital status, Medicaid dual coverage, residence, poverty, frailty, comorbidities, year of diagnosis, extranodal disease, stage, 1st line regimen, and duration of 1st line therapy. We used Cox regression model to compare all-cause mortality (AM) and reported hazard ratio (HR) with 95% confidence interval (CI). We conducted competing risk analysis for mortality from MCL (MFM; competing event [CE]: non-lymphoma mortality [NLM]) and initiation of 2nd line therapy (CE: AM), respectively, reporting sub-HR (sHR). Results: Of 1579 older adults treated for MCL, BR (37%) and RCHOP (17%) were the most common 1st line regimens. Among those receiving BR/RCHOP, 44% received RM. Only 3% received SCT. Use of RCHOP decreased substantially over time (2007: 31%, 2017: 5%, P for time trend<0.001), with an increase for BR (2007:1%, 2017: 41%, P<0.001). We included 386 patients who received either RCHOP (83) or BR (303) (post-PSM; median age: 75, 67% men, 95% White) to examine effectiveness of RM, and all covariates were well balanced. Compared to patients not receiving RM, AM (HR: 0.59, 95% CI: 0.42-0.84), MFM (sHR: 0.53, 95% CI: 0.35-0.81) and initiation of 2nd line therapy (sHR: 0.60, 95% CI: 0.44-0.82) were all significantly lower in patients receiving RM. NLM was similar between RM and non-RM groups, suggesting that PSM worked well. Conclusions: Our population-based real-world analyses showed significant benefits of RM in survival and disease control among older patients with MCL who did not receive SCT, despite the shift from RCHOP to BR as 1st line induction regimen.
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