Autophagy Induction After Bortezomib for Myeloma

PRIMARY OBJECTIVE:

The primary objective of this study is to determine whether administration of bortezomib
leads to an increase in cellular autophagy, as determined by electron micrographs of
peripheral blood lymphocytes and primary myeloma cells in patients receiving single-agent
bortezomib.

SECONDARY OBJECTIVES

1. To determine the optimal timing of autophagy assessments for patients receiving
bortezomib.

2. To explore whether high levels of autophagy are associated with resistance to
bortezomib therapy.

3. To validate our primary assay by confirming baseline stability of the number of
autophagic vesicles per cell

4. To compare results of autophagy measurements in peripheral blood mononuclear cells and
bone marrow plasma cells

Inclusion Criteria:

- Histologically confirmed multiple myeloma (both newly diagnosed and relapsed patients
are permitted)

- No more than one line of prior therapy containing bortezomib. No prior therapy with
any other proteasome inhibitor.

- For subjects who received previous bortezomib, at least a partial response while on
the bortezomib-containing therapy, without progression while on bortezomib-containing
therapy or within 90 days of stopping bortezomib.

- Planned therapy, as determined by the patient's treating physician, with a
bortezomib-containing regimen

- Medically suitable to undergo study procedures, including a one-week washout of prior
therapy, one week of observation, and one week of single-agent bortezomib

- Provision of written informed consent

Exclusion Criteria

- Age <18 years (though the demographics of myeloma make it highly unlikely that any
children will meet inclusion criteria)

- Treatment with other anti-myeloma agents, including corticosteroids, thalidomide, or
lenalidomide, within the 7 days prior to the study baseline bone marrow biopsy.

- Inability to understand the informed consent document or unwillingness to consent.

- Written informed consent must be obtained from all patients before study entry.