Total marrow irradiation and peripheral blood progenitor cell rescue following high-dose melphalan and peripheral blood progenitor cell rescue in patients with multiple myeloma

Abstract

Tandem high-dose therapy (THDT) followed by peripheral blood progenitor cell reinfusion (PBPC) is associated with a projected 20% progression-free survival at 7 years after treatment for patients with multiple myeloma (MM). Combining standard fractionated total body irradiation (TBI) with high-dose melphalan precludes optimal dosing of melphalan, and results in equivalent efficacy but more toxicity in comparison to high-dose melphalan (mel) alone. Helical tomotherapy is a novel tool for delivering CT image guided intensity modulated radiation therapy and may allow for greater doses of total marrow irradiation (TMI) and less collateral damage to other organs. We set out to test the feasibility of THDT inclusive of TMI. Eligible patients (≤70 years old, with stages I-III MM, in response or with stable disease, with a creatinine clearance of ≥50 mL/min) underwent mobilization with cyclophosphamide 1.5 gm/m2 and G-CSF 10 microgram/kg and procurement of ≥ 4 × 106 CD34+ cells/kg. THDCT consisted of a set dose of mel 200 mg/m2 followed by PBPC. At a minimum of 6 weeks later, TMI 200 cGy daily × 5 days, (to be escalated up to 200 cGy twice daily in a standard phase one cohort by cohort fashion) an PBPC is administered. Upon recovery, thalidomide 50–200 mg daily and dexamethasone 40 mg/day × 4 days every 28 days is to be prescribed. At dose level 1 (TMI: 200 cGy daily × 5 days) two patients (a 53 year old female with stage I MM in complete response and a 48 year old male with stage III MM in partial response prior to THDT) have completed THDT and are currently receiving maintenance. Neutrophyl and platelet recovery following TMI was observed by days 9 and 11, and platelet independence (defined as the day after the last platelet transfusion) was observed by day 10. Grade 1 emesis and grade 2 nausea, but no evidence of oral mucositis, enteritis, or skin erythema were noted. The estimated reduction in organ exposure to radiation with TBI versus TMI ranged from 6.5–6.9-fold (lens) to 2.5–2.6-fold (bowel), and 1.4–1.7-fold (lungs) in the first two patients treated. TMI is feasible for patients undergoing THDT for MM. Accrual is ongoing and results in patients treated at higher doses of TMI will be presented.