Response to influenza and pneumococcal vaccination in myeloma patients treated with Lenalidomide with/without steroiden.

Patients with MM who are treated with lenalidomide with or without steroids or
chemotherapy are at risk of developing infections. Vaccination with influenza
vaccine and pneumococcal vaccine might protect patients against these pathogens.
In this study the humoral and cellular immune response to vaccination is
investigated in patients with multiple myeloma who are treated with
lenalidomide with/without steroids or chemotherapy.

To compare the number of responders to vaccination with the influenza virus
vaccine and pneumococcal vaccine at different time points in treatment cycle of
lenalidomide. Secondly to study the immune-response to vaccination, during
treatment with lenalidomide with/without steroids and/or chemotherapy in
relation to the immunesystem.

The design is a randomised trial. A control group is established as reference
for response to influenzavaccination and for normal values of immune system
components which play a role in the pathophysiology of multiple myeloma (to
answer the second objective). A total of hundred (100) patients with multiple
myeloma, who are treated with lenalidomide with or without
steroids/chemotherapy, will be included. Patients will be randomised in 2
groups: the first group will be vaccinated on day 1 of a treatment cycle of
lenalidomide (= early group), the second group will be vaccinated on day 20 (=
late group). These 2 groups will be compared to each other. The control group
will consist of 40 age, sex and co-morbidity matched controls who are recruited
at the general practioner.

All patients and matched controls will receive the influenza virus vaccine
Influvac® or Vaxigrip® which will be used in the authorised form according to
existing vaccination protocol for immune compromised patients. Influenza
vaccine will be delivered to each participating hospital by the RIVM. Secondly
they will receive Prevnar 13, a pneumococcal conjugate vaccine which will be
used in the authorised form. At two different time points before and after
vaccination sera will be taken and investigated.

Patients will be vaccinated with the annual influenza vaccine that is indicated
for this patient group according to existing vaccination protocols in immune
compromised patients. A second vaccination with a pneumococcal vaccine will be
given. Blood samples will be drawn before the vaccination and three weeks after
vaccination, so two blood samples will be drawn. If possible, vaccination will
be integrated in normal out-patient clinical visits. The vaccines will be used
in the authorised form and for the authorised purpose, therefore no additional
risks are to be expected. Patient discomfort might consist of a painful arm/leg
after vaccination. Adverse events which are common (0.1-1%) include headache,
fever, myalgia, artralgia, nausea, vomiting, and pain and redness at the
vaccination spot. Rare events are allergic reactions (very rare leading to
shock), angio edema, neurologic disorders and urticaria. Benefit is protection
against infection with the influenza virus or infection with s.pneumoniae.