Efficacy of a predefined vitamin D dosing regimen in vitamin D-insufficient multiple myeloma patients.

Randomized controlled studies have shown that the introduction of the 'new
agents' bortezomib, thalidomide and lenalidomide resulted in improved response,
progression-free survival and overall survival. However, vitamin D
insufficiency is a frequent problem for patients with multiple myeloma. In
addition, there is a high prevalence of peripheral neuropathy among these
patients. Several studies have shown that an adequate vitamin D level has
several advantages for the human body, such as improvement of muscle function
and the immune system. Obtaining an adequate vitamin D level in patients with
multiple myeloma is therefore a major gain in which the quality of life can
improve or decrease less quickly. Vitamin D deficiency is also associated with
many complications, such as a decrease in bone density and possibly peripheral
neuropathy. This is why we think it is our duty of care to supplement vitamine
D-insufficient patients with vitamin D.

The primary objective of this study is to determine the efficacy of a
predefined vitamin D dosing regimen on the prevalence of vitamin D
insufficiency in MM patients.

Secondary objectives are to detect the influence of several variables (age,
gender, cumulative dose, type of treatment, race, the use of alcohol and the
presence of diabetes mellitus) on the chance of successfully increasing the
vitamin D serum concentration; to determine the efficacy of vitamin D
supplementation on the prevalence and severity of PN in vitamin D-insufficient
MM patients; to determine differences between the effect of vitamin D
supplementation on the prevalence and severity of PN for each subgroup:
treatment and individual drugs used for MM (drugs that can be used are
bortezomib, carfilzomib, daratumumab, elotuzumab, ixazomib, lenalidomide,
panobinostat, pomalidomide, thalidomide and vincristine).

This is an intervention study. Patients who participated in study protocol
*Vitamin D status and peripheral neuropathy in multiple myeloma patients* will
be screened, and patients who meet the inclusion criteria will be asked to
participate in this study. The result of this first study will be used as
baseline measurments for the follow-up study if the measurments are not older
than 3 months. If they are, a new baseline measurement will be performed.
Patients in the study group will receive vitamin D supplementation. The vitamin
D serum levels will be measured after two months, to ascertain a vitamin D
level > 75 nmol/L. When necessary, another loading dose and dose adjustments
can be made to accomplish an accurate level. After 3 months, the vitamin D
serum levels will be measured again to ascertain a vitamin D level * 75 nmol/L.
If the level does not exceed 75 nmol/L, another dose adjustment will be made.
After 6 months, vitamin D levels will be determined in all patients. In
addition, each patient will complete the ICPNQ questionnaire and VAS score
after two months and at end of follow-up after six months.

Patients receive vitamin D supplements for six months and will receive a
vitamin D loading dose no more than twice. In addition, every patient will
complete the ICPNQ and VAS score after 2 and 6 months to determine neuropathy
grading. After 1, 2, (possibly 3) and 6 months blood samples will be taken. If
the baseline measurement is older than 3 months, a new baseline measurement
will be performed. This consists of a new blood sample, the ICPNQ and VAS
scores.

Vitamin D deficiency is associated with many complications, for example a
decrease in bone density and possibly peripheral neuropathy. As blood sampling
is performed frequently in myeloma patients and the questionnaires can be
filled in within minutes, the burden for the patients is minimal. The patients
do need to take an extra vitamin supplement in addition to the other drugs
needed for treatment. However, vitamin D in doses in this study is reported a
safe intervention without adverse drug reactions. The vitamin D tablets are
used outside the registered indication, but as the indication has not been
restricted due to safety issues of supplementation to patients with vitamin D
levels < 75 nmol/L, and a vitamin D level of > 75 nmol/L is considered
adequate, we will use 75 nmol/L as the threshold value.