Vitamin D deficient patients suffering from diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP have lower overall survival. This especially applies for patients with vitamin D levels ≤8 ng/ml (Bittenbring et al. J Clin Oncol. 2014; 32:3242-8). Vitamin D up to 65 ng/ml may be necessary for optimal efficacy of R-CHOP (Neumann et al. Cancer Immunol Immunother. 2018; 67:1709-18). To study the clinical benefit of vitamin D substitution, we established a fast-track schedule to appropriately substitute patients to these vitamin D levels.

The pre-treatment baseline vitamin D level was determined in 99 patients included in the ongoing, randomized, multicenter, phase-III, open-label OPTIMAL>60 trial (NCT01478542) from November 2014 to July 2015. It was intended that patients reach a vitamin D level of 65 ng/ml. We calculated the dose needed using patient weight and baseline vitamin D: IU = 100 x ΔVitD3 x kg body weight (Van Groningen et al. Eur J Endocrinol. 2010; 162:805-11) and substitution started before treatment. Patients received 20.000 IU capsules of vitamin D, split over several days, with a daily maximum of 200.000 IU. Vitamin D level was checked again after substitution and at all restagings. Patients, who did not reach the intended vitamin D level of 65 ng/ml, received a second or third cycle of substitution.

Baseline vitamin D level was 17.8±12.7 ng/ml. 14.3% of the patients reached the target value of up to 65 ng/ml after one substitution cycle with a mean dose of 386.000±137.000 IU. The average increase was 27.8 ng/ml, to a mean of 45.6±18.7 ng/ml. After the second substitution cycle with a median dose of 188.000±102.000 IU patients had vitamin D serum levels of 52.6±13.8 ng/ml. After a third substitution with 91.000±56.000 IU mean level of vitamin D was 56.0±9.6 ng/ml.

By administering vitamin D in a dosage calculated by the van Groningen formula, we were able to increase the vitamin D level of our patients reliably after 2-3 cycles of substitution. After second and third substitution, a saturation effect was seen. The clinical effect of vitamin D substitution is the subject of the current study and the results are presently pending.

The OPTIMAL>60 trial issupported by Amgen, Roche, Acrotech.

Disclosures

Poeschel:Roche:Other: Travel, Accommodations, Expenses;Amgen:Other: Travel, Accommodations, Expenses;Abbvie:Other: Travel, Accommodations, Expenses.Habersang:Rheinlandklinikum Neuss:Current Employment.Mahlberg:Janssen:Other: Travel, Accommodations, Expenses;Mutterhaus der Borromaeerinnen, Trier:Current Employment;Novartis:Honoraria, Other: Travel, Accommodations, Expenses;Labor Synlab:Ended employment in the past 24 months;Abbvie:Other: Travel, Accommodations, Expenses;Roche:Honoraria;Amgen:Honoraria, Other: Travel, Accommodations, Expenses;Merck:Honoraria, Other: Travel, Accommodations, Expenses.Keller:Janssen-Cilag:Consultancy, Other: Travel, Accommodations, Expenses;Takeda:Consultancy, Other: Travel, Accommodations, Expenses;Celgene:Consultancy, Other: Travel, Accommodations, Expenses;BMS:Consultancy, Other: Travel, Accommodations, Expenses;Roche:Consultancy, Other: Travel, Accommodations, Expenses;Hexal:Consultancy;Novartis:Consultancy;MSD:Consultancy;Pfizer:Consultancy;Astra-Zeneca:Consultancy;Pentixapharm:Consultancy.Viardot:Kite/Gilead:Honoraria, Other: advisory board;Roche:Honoraria, Other: advisory board;Amgen:Honoraria, Other: advisory board;Novartis:Honoraria, Other: advisory board.Stilgenbauer:Novartis:Consultancy, Honoraria, Other, Research Funding;Pharmacyclics:Consultancy, Honoraria, Other, Research Funding;GlaxoSmithKline:Consultancy, Honoraria, Other: travel support, Research Funding;Janssen-Cilag:Consultancy, Honoraria, Other: travel support, Research Funding;Mundipharma:Consultancy, Honoraria, Other, Research Funding;Genzyme:Consultancy, Honoraria, Other: travel support, Research Funding;Genentech:Consultancy, Honoraria, Other: travel support, Research Funding;F. Hoffmann-LaRoche:Consultancy, Honoraria, Other: travel support, Research Funding;Celgene:Consultancy, Honoraria, Other: travel support, Research Funding;Gilead:Consultancy, Honoraria, Other: travel support, Research Funding;AbbVie:Consultancy, Honoraria, Other: travel support, Research Funding;Boehringer-Ingelheim:Consultancy, Honoraria, Other: travel support, Research Funding;Amgen:Consultancy, Honoraria, Other: travel support, Research Funding.Held:Roche:Consultancy, Other: Travel, Accommodations, Expenses, Research Funding;BMS:Consultancy, Other: Travel, Accommodations, Expenses, Research Funding;MSD:Consultancy;Acrotech:Research Funding;Spectrum:Research Funding;Amgen:Research Funding.Bittenbring:Gilead:Honoraria, Other: Travel, Accommodations, Expenses;Bluebird Bio:Honoraria, Other: Travel, Accommodations, Expenses;Roche:Honoraria, Other: Travel, Accommodations, Expenses, Advisory board;Celgene:Honoraria, Other: Travel, Accommodations, Expenses, Advisory Board;Pfizer:Honoraria, Other: Travel, Accommodations, Expenses.

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2020 by The American Society of Hematology
2020
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