Fractures are common within 18 months following first-line R-CHOP in older patients with diffuse large B-cell lymphoma

Abstract

Diffuse 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.

Increased Risk of Hip Fracture in Patients with Lymphoma, a Swedish Population Study of 37,236 Lymphoma Patients

“…Our results are, to some extent, in agreement with other studies on osteoporosis and fractures in patients with hematologic malignancies and specifically lymphoma (132)(133)(134)179). Most of the studies published on osteoporosis or fractures in lymphoma patients hitherto have been small.…”

“…Our cohort was heterogenous, with a mixture of many lymphoma subtypes and included both treated and untreated patients. Additionally, we only included hip fractures while the studies from Denmark and UK included an "osteoporotic event" and all fracture types, respectively, which might partly explain the differences in our results (132,133). In Sweden, the use of rituximab in first line therapy of lymphoma started between 2003 and 2007 (181).…”

“…A Danish case-control study showed a 61% increased risk for osteoporotic events (osteoporosis treatment or low-energy fracture) in patients with DLBCL or FL treated with a R-CHOP-like therapy compared with controls from the Danish population (132). A retrospectively collected UK study on patients ≥70 years treated with R-CHOP, showed a cumulative fracture incidence of 11.4% 18 months after treatment with R-CHOP (133). It is not clear whether it is the lymphoma in itself, the treatment, or other factors that affect the risk for fractures.…”

“…The highest risk increase was seen in women (over 50 years) and older patients (132). Another large retrospective study from UK showed a cumulative incidence of fracture being 11.4%, 18 months after start of R-CHOP, in a cohort of 877 patients 70 years or older with DLBCL (133). No control group was provided but the authors assumed an annual risk of fracture being 2% in the population, based on UK register data (180).…”

Bisphosphonates prevents the bone mineral loss in lymphoma patients treated with glucocorticoids: a prospective, randomized controlled phase 3 trial in China

“…Lymphoma patients were at a signi cant higher risk of an osteoporotic event with a 5-year cumulative rate 10%, in comparison with general population of 6.8% in Denmark [21] . Recently, a study from United Kingdom reported that receipt of R-CHOP in DLBCL patients were at a cumulative risk of 11.4% for bone fracture at 18 months older than 70 years old [22] . In China, an estimated prevalence of osteoporosis to be 6.46% for men and 29.13% for women aged ≥ 50 years [23] .…”