Bortezomib re-induction therapy combined with donor lymphocyte infusion in patients with relapsed Multiple Myeloma following allogeneic stem cell transplantation

Donor lymphocyte infusion is the standard of care for patients with a relapse
following allogeneic stem cell transplantation, resulting in a response rate of
30-40% in myeloma. Velcade (Bortezomib) is registered for relapsed myeloma
resulting in a response rate of 30-40%. We retrospectively found that
combination of both therapies increased response rate dramatically (> 70%). It
seems rational to combine both treatments in patients with relapsed myeloma
following allogeneic stem cell transplantation and test this approach
prospectively.

Primary objectives:
Efficacy of bortezomib combined with DLI in patients with relapse myeloma
following (non) myeloablative allo-SCT as measured by
- response rate including percentage of complete remission according to EBMT
criteria (appendix A)
- Event free survival/EFS (i.e. time from registration to progression or death
from any cause
whichever occurs first) and overall survival/OS.

Secondary objective
- toxicity including evaluation of GvHD and CTC grade toxicity (Appendix B and
C)
- evaluation of immune modulating effects of combined treatment with DLI and
bortezomib as measured by serial plasma samples

Prospective Phase II study

Bortezomib followed by DLI, eventually followed by continuation of Bortezomib
treatment and DLI

The most important side effect of DLI is acute and chronic GvHD which occurs in
about 40 % of patients and will be severe in a small percentage of the patients
(< 10%).
The most important side effect of Bortezomib is polyneuropathy which occurs in
about 40 % of patients and when adequately monitored will not exceed > grade 1.

There are no indications from the retrospective study that side effects become
more severe of more frequent when both therapies are combined.