Hill, Brian

SummaryMantle cell lymphoma (MCL) is clinically and biologically heterogeneous. While various prognostic features have been proposed, none currently impact therapy selection, particularly in older patients, for whom treatment is primarily dictated by age and comorbidities. Herein, we undertook a comprehensive comparison of clinicopathological features in a cohort of patients 60 years and older, uniformly treated with bendamustine and rituximab, with a median survival of >8 years. The strongest prognostic indicators in this cohort were a high‐risk call by a simplified MCL international prognostic index (s‐MIPI) (HR: 3.32, 95% CI: 1.65–6.68 compared to low risk), a high‐risk call by MCL35 (HR: 10.34, 95% CI: 2.37–45.20 compared to low risk) and blastoid cytology (HR: 4.21, 95% CR: 1.92–9.22 compared to classic). Patients called high risk by both the s‐MIPI and MCL35 had the most dismal prognosis (HR: 11.58, 95% CI: 4.10–32.72), while those with high risk by either had a moderate but clinically relevant prognosis (HR: 2.95, 95% CI: 1.49–5.82). A robust assay to assess proliferation, such as MCL35, along with stringent guidelines for cytological evaluation of MCL, in combination with MIPI, may be a strong path to risk‐stratify older MCL patients in future clinical trials.

SummaryIn young and fit patients with mantle cell lymphoma (MCL), intensive induction therapy followed by a consolidative autologous haematopoietic cell transplant (autoHCT) is the standard of care in the front‐line setting. Recently, time‐to‐event analysis has emerged as an important risk assessment tool in lymphoma, though its impact in MCL is not well defined. We utilized the Center for International Blood and Marrow Transplant Research database to evaluate the effect of post‐autoHCT time to relapse on overall survival (OS) over time in 461 patients who underwent autoHCT within 12 months of MCL diagnosis. On multivariate analysis, the impact of relapse on OS was greatest at the six‐month [hazard ratio (HR) = 7·68], 12‐month (HR = 6·68), and 18‐month (HR = 5·81) landmark timepoints. Using a dynamic landmark model we demonstrate that adjusted OS at five years following each landmark timepoint improved with time for relapsing and non‐relapsing patients. Furthermore, early relapse (<18 months) following autoHCT defines a high‐risk group with inferior post‐relapse OS. This retrospective analysis highlights the impact of time to relapse on OS in MCL patients undergoing up‐front autoHCT and emphasizes the need to consider novel therapeutic approaches for patients suffering early relapse.

SummaryBendamustine (B) with rituximab (R) is a standard frontline treatment for medically fit follicular lymphoma (FL) patients. The safety and efficacy of maintenance rituximab (MR) after BR induction has not been formally compared to observation for FL, resulting in disparate practice patterns. Prospective trials have shown benefit of MR after R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or R‐CVP (rituximab, cyclophosphamide, vincristine, prednisone), yet recent data from the GALLIUM study comparing outcomes of patients treated with chemotherapy with R or obinutuzumab (G) showed higher than anticipated fatal adverse events with BR/BG. In order to assess the efficacy and tolerability of MR after BR, we retrospectively collected data on 640 newly diagnosed patients treated with FL. We found that patients who achieved partial remission (PR) after ≥4 cycles of BR had improved duration of response (DOR) with MR vs. no maintenance, whereas those in complete remission did not. These findings were confirmed in a validation cohort. In the entire study population, the known fatal adverse event rate after BR was 2·5% and did not significantly differ in those receiving MR versus no maintenance. [Correction added on 14 January 2019, after online publication: The preceding sentence has been corrected in this current version.] Within the limitations inherent to retrospective analysis, these data suggest that FL patients with a PR to BR experience prolongation of remission with MR with an acceptable safety profile.