Salvage and Hematopoietic Recovery With Bortezomib and Melphalan In Cytopenic Recurrent and Refractory Multiple Myeloma

Abstract

The management of relapsed and refractory multiple myeloma (RRMM) remains difficult. Patients have short response duration, become cytopenic and are not eligible for clinical trials of promising new drugs. They often have inadequate numbers of stem cells (<3 × 10(6) CD34/kg) remaining for a myeloablative transplant. Thus, new approaches are needed. We therefore initiated a pilot clinical trial to enable the successful reconstitution of blood counts in patients with RRMM so they could proceed onto new clinical trials and test the synergy of bortezomib and melphalan clinically in non-myeloablative doses (stem cell boost). We have treated 9 patients with RRMM who have failed novel agents (including bortezomib) and chemotherapy (dexamethasone, cytoxan, etoposide, cisplatin, and doxil) and who had only limited duration of response previously with high dose melphalan. All patients were cytopenic (ANC < 1000 and/or platelets < 50,000/ mcl) and thus not eligible for new clinical trials. The melphalan was given at 30–50 mg/m2 on days 1 and 4, depending on the age and performance status of the patient. Bortezomib at 1.3 mg/m2 was given on the same days after the melphalan. The patients then received 1.5 to 2.2 × 10(6) CD34 cells/kg. (depending upon the amount of remaining stem cells). We have seen responses (>25%) in all 9, with >PR in 8 and VGPR in 1. More importantly, all patients successfully engrafted WBC >2000 and platelets >50,000/mcl. Duration of response was 2 months or greater and all patients were able to proceed on to new clinical trials. All patients were given treatment as outpatient and average duration of hospitalization was 3 days (range 0 to 6) during cytopenia. Thus, the clinical synergy between bortezomib and melphalan can lead to an effective salvage strategy even for cytopenic patients with relapsed and refractory multiple myeloma. This non-myeloablative approach could serve as a platform for proceeding on to new clinical trials for those advanced patients without adequate numbers of stem cells for a myeloablative transplant.