Phase I study of bortezomib and 153Sm-lexidronam combination for refractory and relapsed multiple myeloma

Abstract

7614 Background: Multiple myeloma (MM) is a highly radiosensitive B-cell malignancy and radiation therapy has been an effective treatment for these patients. Recent preclinical studies have demonstrated that the bone-seeking radionuclide, Samarium Sm153 lexidronam (Sam) in combination with the proteasome inhibitor, bortezomib (Vel), can synergistically inhibit proliferation of myeloma cell lines in vitro and reduce MM growth in mice bearing human MM without significant myelotoxicity. These results provide the basis for a new therapeutic approach of combining Vel and Sam to overcome resistance and to minimize nontumor tissue toxicity among refractory and relapsed MM patients. Methods: The primary objective of this Phase I study is to determine the response rate and tolerability of Vel + Sam combination in patients with relapsed or refractory MM. Patients will be enrolled on this Phase I dose-escalation trial which involves six cohorts. Previous treatment with Vel is permissible. Dose escalation in parallel arms is as follows: A complete treatment cycle is 8 weeks. Vel is given on days 1, 4, 8 and 11 followed by a 45-day rest period. Sam is administered on day 4. The cycle is repeated on Day 57 if disease is stable or improved and platelets and neutrophils recover to at least grade 1 toxicity. DLT is defined as cycle 1 grade 4 hematologic or grade ≥3 non-hematologic toxicity. Results: Cohorts 1 and 4 have been enrolled (3 patients per cohort). One cycle of treatment has been completed thus far. No significant toxicity has been observed except a transient fever in one patient. There have been no dose limiting toxicities to date. The first six patients will be evaluated for response within the next two weeks. Conclusions: The trial will continue to enroll patients in cohorts 2 and 5. Updated results from the trial will be presented at the meeting. [Table: see text] [Table: see text]