Abstract

AbstractDiffuse large B-cell lymphoma (DLBCL) and osteoporotic fracture are both more common in older patients. Exposure to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) is likely to increase the risk of fracture, but evidence is lacking to define fracture incidence in this group. Data on consecutive patients with DLBCL aged ≥70 years treated with 1 to 8 cycles of full or attenuated R-CHOP were retrospectively collected across 10 UK centers (2009-2019). Patients were followed up from starting R-CHOP for a minimum of 6 months and censored at 18 months; at last follow-up if <18 months; or at progression or death. Of 877 patients identified, 148 were excluded: 121 had progression or died before 6 months; 23 had follow-up <6 months. Across 729 remaining patients, the median age was 77 years, and 68% had an Eastern Cooperative Oncology Group performance status of 0 to 1. Eighty-one fractures occurred within 18 months of follow-up; 42 were symptomatic, including 30 requiring hospital attendance or admission. The cumulative fracture incidence was 6.2% (95% confidence interval [CI], 4.7-8.2) at 6 months; 9.7% (95% CI, 7.8-12.1) at 12 months; and 11.4% (95% CI, 9.3-14.0) at 18 months. Multivariate analysis identified a predisposing history (osteoporosis, osteopenia, prior fracture, and rheumatoid arthritis [RhA]), DLBCL bone involvement at baseline, and receipt of prephase steroids as independent risk factors for fracture. There is a clinically relevant fracture risk and significant associated morbidity in older patients receiving R-CHOP. Careful attention to bone health is warranted in older patients receiving R-CHOP. Randomized studies are required to better define the most effective strategies to reduce fracture risk.

Highlights

  • Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy, with the highest incidence in older patients.[1]

  • We were interested in the patient fracture risk for those who had survived without progression beyond 6 months; any patient who had progressive disease (PD) or died within 6 months of the start of cycle 1 R-CHOP (R-CHOP1) were excluded

  • The current analysis is the largest published series reporting the incidence, identifiable risk factors, and characteristics of fractures occurring after R-CHOP in this specific age cohort of patients with DLBCL

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Summary

Introduction

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy, with the highest incidence in older patients.[1] Full-dose or attenuated R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) produces durable remissions in 60% to 70% of older. Submitted 5 June 2020; accepted 15 July 2020; published online 11 September 2020. 22 SEPTEMBER 2020 x VOLUME 4, NUMBER 18. Historical epidemiologic studies have identified an association between the treatment of non-Hodgkin lymphoma (NHL) with steroid-containing chemotherapy and increased fracture rates during the following year.[5] Follow-up of 111 adult patients treated with R-CHOP, the most commonly used front-line regimen for DLBCL, showed a reduction in bone mineral density (BMD) at 1 year with incomplete recovery at 2 years and a rate of vertebral fracture of 14% on routine surveillance computed tomography (CT) scans; additional fracture sites and symptomatic fracture events were not assessed, .[6]

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