Rituximab Maintenance Improves Time-to-Next Treatment and OS in Patients With Mantle Cell Lymphoma

Gilles Salles, MD, PhD

Time-to-next treatment (TTNT) and overall survival (OS) were improved in a real-world study evaluating patients who received rituximab (Rituxan) maintenance after first-line treatment with bendamustine and rituximab (BR) or R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with mantle cell lymphoma (MCL), according to a retrospective analysis presented at the European Hematology Association 2021 Virtual conference.

The real-world TTNT rate was higher with first-line BR followed by rituximab maintenance versus first-line R-CHOP followed by rituximab maintenance, according to lead author Gilles Salles, MD. Salles, the lymphoma service chief at Memorial Sloan Kettering Cancer Center in New York, New York, noted, however, that real-world evidence is limited regarding how rituximab maintenance is used in routine clinical practice, especially after first-line treatment of BR.

The real-world TTNT rate at 36 months for patients who received BR alone was 51% (95% CI, 46%-55%), and for patients who received BR plus rituximab maintenance, it was 75% (95% CI, 70%-70%; P < .001). The real-world TTNT rate at 36 months for patients who received R-CHOP alone was 38% (95% CI, 32%-45%), and for patients who received R-CHOP plus rituximab maintenance, it was 66% (95% CI, 59%-74%; P < .001).

Regarding the real-world OS rate at 36 months, for patients who received BR alone, the rate was 76% (95% CI, 72%-80%) and for BR plus rituximab maintenance, it was 85% (95% CI, 81%-89%; P = .001). For patients who received R-CHOP alone, the rate was 77% (95% CI, 72%-83%), and for R-CHOP plus rituximab maintenance, the rate was 88% (95% CI, 83%-93%; P = .030).

De-identified electronic health records of adults diagnosed with MCL were collected from the Flatiron Health Database from January 2011 to January 2021, from 280 cancer clinics with 800 sites of care (n = 4216). Patient characteristics, treatment patterns, and efficacy outcomes, including real-world TTNT and real-world OS underwent multivariate analysis.

At baseline, patients who received BR with rituximab were older compared with patients treated with R-CHOP, and over 90% of patients were treated in the community versus the academic setting.

Patient were divided into 3 cohorts: patients who received first-line treatment (n = 3614) with a median follow-up of 45.5 months (95% CI, 43.4-48.1); patients who received first-line BR or R-CHOP (n = 2317); and patients who were rituximab maintenance-eligible (n = 1621). There were 602 patients with no record of first-line MCL treatment.

The latter cohort was further subdivided into BR only (44.9%; n = 728), BR plus rituximab maintenance (28.3%; n = 458), R-CHOP only (15.7%; n = 255), and R-CHOP plus rituximab maintenance (11.1%; n = 180).

In comparing the BR group with the R-CHOP group, a lower proportion of patients with high or intermediate Mantle Cell Lymphoma International Prognostic Index (MIPI) score was observed in the BR group. Similarly, a lower proportion of patients in the BR group underwent stem cell transplant according to the investigators.

In patients receiving first-line BR alone versus BR plus rituximab maintenance, BR plus rituximab maintenance was less commonly used in patients with ECOG performance > 2 (11.3% vs 7.7%) and high-risk MIPI (35.5% vs 23.6%) versus BR alone.

“When looking at the efficacy outcome among the 4 subgroups, we see that rituximab maintenance is clearly associated with improved real-world time-to-next treatment following both BR and R-CHOP,” Salles said. “The highest 36 months real world time-to-next treatment rate was seen with BR plus rituximab maintenance at 75%. OS rates were similarly high with both BR and R-CHOP followed by rituximab maintenance at around 85 to 88%,” continued Salles.

Overall, patient and disease characteristics associated with significantly shorter real-world TTNT and real-world OS included age ≥ 65 years, lactate dehydrogenase/upper limit normal ≥ 1, bulky disease, and blastoid/pleomorphic morphology.

“Multivariate analysis showed that the use of rituximab maintenance was associated with superior real-world TTNT and OS,” Salles said. “This was consistent when the analysis was performed separately in BR- or R-CHOP-treated patients.”

Salles cautioned that selection bias is inherent in real-world analysis and that the results need to be interpreted in the context of evidence provided by randomized studies assessing rituximab maintenance in MCL.

“The potential benefit of adding rituximab to BR following rituximab maintenance in patients with previously treated MCL is being evaluated in the phase 3 SHINE study [NCT01776840],” Salles said. “These results are expected in the near future,” concluded Salles.

_Reference

_{Salles G, Wang M, Kumar A, et al. Role of maintenance rituximab (MR) after first-line (1L) bendamustine + rituximab (BR) or R-CHOP in patients (pts) with mantle cell lymphoma (MCL) from a large US real-world (RW) cohort. Presented at: European Hematology 2021 Congress. June 9-12, 2021. Abstract EP785.}