Session Item

Radiation therapy had been tested at ablative doses for total body irradiation (TBI) in combination with melphalan (MEL) for multiple myeloma (MM), but was shown to be prohibitively toxic. In order to ameliorate toxicity, total marrow irradiation (TMI), an image-guided organ sparing form of TBI, was given as the sole ablative modality during the second cycle of tandem autologous transplant (TAT) for patients with stable/responsive MM as part of a Phase I-II trial. Herein we provide long-term follow-up.

We enrolled patients with MM in response or with stable disease. Patients had to be ≤ 70 years old and ≤ 18 months from diagnosis of MM. They received MEL 200 mg/m2 and AT (Cycle 1), and, after recovery, TMI (1000-1800 cGy; maximum tolerated dose [MTD]: 1600 cGy) and AT (Cycle 2) followed by maintenance with thalidomide or lenalidomide, and dexamethasone monthly for up to 12 months. TMI target volumes included all skeletal bone except mandible and maxillary bones to minimize oral cavity dose and mucositis. Radiation treatment plans were designed using the Hi-Art Tomotherapy treatment planning system such that a minimum of 85% of the target volumes received the prescription dose.  Kaplan-Meier method was used to assess survival. The first patient enrolled in 1/2005 and follow-up was updated through 6/2021.

A total of 54 patients were enrolled. The median age was 54 years (31-66); 31 patients were male. The median time between MM diagnosis and AT was 8 months (3-16). Durie Salmon stages were: I (N=7), II (N=16), III (N=31) and retrospectively calculated ISS stages were: I (N=32), II (N=15), III (N=7). High-risk cytogenetics [t(4;14) (n=1), a variant of t(4;14), or del 17/p53 (n=4)] were observed in 11% of patients. Forty-four of 54 patients (81.5%) received TAT per-protocol. Thirty patients (55.6%) received TAT at the MTD TMI dose of 1600 cGy. Median follow-up among survivors was 12 years (range: 9.2-15.5+). There were no graft failures. Secondary malignant neoplasms included one each of acute myeloid leukemia, papillary thyroid, prostate, and in situ breast carcinoma, and melanoma, and 4 patients with non-melanoma skin cancers. In intent-to-treat analysis, median PFS and OS were 2.8 years (range: 0.3-15.5+) and 7.7 years (range: 0.5-15.5+), respectively. PFS and OS at 10 years is 20.4% (95% CI 10.9-31.9) and 38.8% (95% CI: 25.9-51.5).  For patients enrolled at the MTD of 1600 cGy, the PFS and OS at 10 years were 26.7% (95%CI: 12.6-43.0) and 46.2% (95%CI: 27.8-62.7) and median PFS and OS were 4.0 years (range:0.3-14.1+) and 9.3 years (range: 0.5-14.1+), respectively. 

Ablative dose TMI as part of TASCT showed favorable long-term toxicity and outcomes given the systemic therapies available at the time of trial enrollment. The inclusion of TMI as a conditioning regiment for MM prior to ASCT may warrant further study in the context of modern induction and maintenance therapies.