Session Item

A second intensification is an option at first relapse in multiple myeloma (MM) after more than 36 months of initial remission. Many conditioning regimens have been tested, with or without total body irradiation (TBI). Recently, it was found that TBI could be replaced by total marrow irradiation (TMI) using helical Tomotherapy with promising results.

This study was a prospective multicenter phase 1 trial which aimed to determine the maximum tolerated dose (MTD) of TMI administered in association with melphalan 140 mg/m², followed by autologous stem cell transplantation (ASCT) as consolidation at first relapse in MM. Four dose levels were explored: 8 Gy, 10 Gy, 12 Gy, and 14 Gy. The dose-limiting toxicity (DLT) was defined as: grade 4 neutropenia > 15 days, grade 4 thrombopenia > 28 days, and all other grade 4 non-hematologic toxicities except nausea, vomiting, alopecia, mucositis, and reaction to autologous stem cell infusion.

Thirteen patients were included: only one DLT at the third escalated dose level (12 Gy) was observed, whereas one patient was treated at 14 Gy with no adverse event. The MTD was not reached. The rate of acute toxicity was low: 38% of grade 3/4 diarrhea, mucositis, or unexplained fever. Regarding the lungs, the mean dose administered was systematically less than 8 Gy. After a median follow-up of 55 months, 70% of participants were alive. Of the 13 patients, 38.5% were in very good partial response (VGPR) and 30.8% in complete response (CR). Three of them were progression-free. Six patients were long survivors, still alive after 55 months of follow-up.

TMI provides good results with a good tolerance profile at first relapse in MM. TMI makes it possible to increase the dose delivered to the PTV while sparing organs at risk (OAR). This technique could be discussed for all regimens before auto- or allo-stem cell rescue when TBI is required.