PF304 OSTEOPOROSIS AND LOW‐ENERGY FRACTURES AFTER TREATMENT FOR LYMPHOMA WITH CORTICOSTEROID‐CONTAINING IMMUNOCHEMOTHERAPY: A DANISH NATIONWIDE COHORT STUDY
Authors: Baech J. , Hansen S.M. , Øvlisen A.K. , Jakobsen L.H. , Jensen P. , Severinsen M.T. , Brown P.D. N. , Vestergaard P. , Frederiksen H. , Jørgensen J. , Starklint J. , Josefsson P. , Hammer T. , Clausen M.R. , Torp‐Pedersen C. , El‐Galaly T. 
Published: June 2019

Background:

Glucocorticoid‐induced osteoporosis is a well‐known adverse event following treatment with glucocorticoids. Commonly used immunochemotherapy regimens for diffuse large B‐cell lymphomas (DLBCL) and follicular lymphomas (FL) such as R‐CHOP, R‐CHOEP, and R‐CVP contain repeated short cycles of prednisolone for up to 8 cycles, resulting in cumulative dosage of up to 4000 mg or an average dosage of 24 mg/day over 24 weeks (8 x R‐CHOP‐21). There is currently no standard of care against detrimental effects of immunochemotherapy on bone mineral density.

Aims:

In a nationwide cohort study, we investigated the incidence of osteoporosis and/or low‐energy fractures (OLEF) in lymphoma patients treated with glucocorticoid‐containing immunochemotherapy and compared findings to a matched background population.

Methods:

Adult patients (>16 years) with newly diagnosed DLBCL and FL between 2000–2012 were retrieved from the Danish Lymphoma Registry. Only patients receiving R‐CHOP, R‐CHOEP, or R‐CVP were included. Patients identified in the Danish National Patient Registry with OLEF prior or during lymphoma treatment were excluded. A background population was constructed by matching 5 random individuals from the Danish Civil Registry per patient matched on sex, month/year of birth and without previous OLEF at the inclusion date (end of treatment for the index patient). Outcome was defined as OLEF and identified from Danish National Patient Registry using ICD‐10 codes. Prescriptions of bisphosphonate, teriparatid, raloxifen, strontium, or denosumab according to the Danish National Prescription Registry were also used as proxies for osteoporosis. Follow‐up was measured from completion of first‐line chemotherapy to OLEF or the end of the study in December 2014. Relapses and deaths were considered competing events in the analysis. Patients were stratified according to estimated dosage of prednisolone. Univariate‐ and multivariable Cox regressions were performed to assess the relationship between glucocorticoid‐containing immunochemotherapy and OLEF.

Results:

2,154 DLBCL and 626 FL patients were matched to 13,900 random Danish individuals. Median follow‐up was 6.0 years. Patients treated with glucocorticoid‐containing immunochemotherapy had 1‐, 5‐, and 10‐year cumulative risks of OLEF at 4%, 12%, and 18%, whereas corresponding risks for controls were 2%, 8%, and 15%. Adjusted for Charlson comorbidity index, and previous breast cancer, prostate neoplasm, liver‐, kidney‐ and thyroid disease, the OLEF‐specific hazard ratio (HR) for lymphoma patients treated with prednisolone compared to matched controls was 1.42 [1.22;1.64]. The same HR was 1.54 [1.18;2.01] for men (breast cancer not included) and 1.36 [1.14;1.63] for women (prostate neoplasm not included). The HR was 1.54 [1.25;1.88] for patients <70 years and 1.40 [1.12;1.74] for ≥70 years. In a sub‐analysis of lymphoma patients only, female gender, increasing age, prior breast cancer, and radiotherapy were associated with a higher risk of OLEF in the multivariable Cox regression (Table 1).

Summary/Conclusion:

Lymphoma patients treated with glucocorticoid‐containing immunochemotherapy face increased risks of OLEF. Female, elderly, and patients treated with radiotherapy or suffering from previous breast cancer appears to be at particularly high risk and may benefit targeted screening for osteoporosis or bisphosphonate prophylaxis during lymphoma treatment.

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