Abstract 3151


Ablative dose total body irradiation (TBI) of 800 cGy in combination with high-dose melphalan (MEL) as part of single cycle autologous transplantation (AT) was found to be too toxic, and therefore inferior, in comparison to MEL. We set out to test total marrow irradiation, (TMI), a “sculpted” form of targeted total body irradiation using image-guided intensity modulated helical tomotherapy, given as the sole ablative regimen during the second cycle of tandem AT (TAT) as consolidation in patients with stable/responsive myeloma.

Patients and Methods:

Patients with Durie-Salmon stages I-III multiple myeloma in response or with stable disease, who were ≤ 70 years old and within 18 months from diagnosis, were enrolled. Patients received MEL 200 mg/m2 and AT (cycle 1), and, following recovery, TMI and AT were administered (cycle 2) at a median of approximately 2 months after the first AT. During the phase I part, TMI was tested between 1000 cGy and 1800 cGy given twice daily × 5 days. The maximum tolerated dose (MTD) –as previously reported- was established at 1600 cGy [Somlo et al. Clin Cancer Res. 2011; 17 (1):174–82]. Following cycle 2 of TAT, maintenance therapy consisted of dexamethasone 40 mg/day × 4 days and an IMiD (first thalidomide, and during the phase II portion, lenalidomide) in a 28-day cycle, administered for 6 cycles for patients in complete response (CR), or for a minimum of 12 cycles for pts not in CR.


54 patients were enrolled (23 females, 31 males). The median age was 54.2 years (range 31.5–66.9). All patients with stage I (7), II (14), III (n=33) multiple myeloma received MEL. Forty-three patients (79.6%) received TMI, 30 at the MTD (6 enrolled at the MTD did not receive TMI). Reversible grade 3 non-hematologic toxicities following TMI at the MTD included febrile neutropenia (5/30), electrolyte abnormalities (7/30), sepsis/infection (5/30), anorexia (2/30), nausea/vomiting (2), fatigue (1), syncope (1). Grade 3 late toxicities include 1 case each of fatigue, nausea, 1 myositis and transaminitis. There were no primary or secondary graft failures, or second malignancies. Of the entire cohort of 54 patients, by intent to treat analysis best responses following TAT included CR (n: 20), very good partial response (VGPR, n:11), partial response (PR, n:16). At a median follow-up of 39 months from first AT, progression-free survival is 55% (95% CI 42–73%) and overall survival is 81% (95% CI 70–94%). For patients treated at the MTD of TMI 1600 cGy, at a median follow-up of 39 months from the first AT, progression-free survival (PFS) is 66% (50–88%), and overall survival (OS) is 80% (65–99%).


TMI of 1600 cGy is feasible as ablative therapy following recovery from high-dose melphalan and AT. CR and VGPR rates are expected to improve with time on maintenance therapy and such data as well as progresion-free and overall survival will be updated. Safety and progression-free and overall survival data are encouraging, and further assessment of the role of TMI is warranted in combination with MEL as part of either single AT, part of TAT, or in comparison of tandem versus single ablative therapy, both in the upfront, and salvage settings.


Off Label Use: IMiDs as maintenance.

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Author notes


Asterisk with author names denotes non-ASH members.