TMI, fludarabine, melphalan pass phase I trial as conditioning therapy in multiple myeloma

Fludarabine, melphalan, and total marrow irradiation (TMI) 900 cGy may be utilized as conditioning for allogeneic stem cell transplantation in patients with high-risk or relapsed/refractory multiple myeloma, as shown in a phase I trial.

Eighteen patients were recruited to join one of two strata in this study. Those with no prior radiation received TMI (900 cGy), fludarabine, and melphalan conditioning, and bortezomib was added in the second cohort (stratum I). Patients with prior radiation received fludarabine, melphalan, and bortezomib without TMI (stratum II).

Eight patients were enrolled in the TMI arm (stratum I). In cohort 1, one of three patients had dose-limiting toxicity (DLT), resulting in the expansion to three more patients with no DLT. In cohort 2, only two patients were included due to low accrual (with bortezomib 0.5 mg/m²); none of them had DLT.

In the non-TMI arm (stratum II), nine patients were included: three in cohort 1 (bortezomib 0.5 mg/m²), of whom none had DLT; three in cohort 2 (bortezomib 0.7 mg/m²), of whom one had DLT. The cohort then expanded to three more patients; another patient experienced DLT.

The median overall survival was 44.5 months (95 percent confidence interval [CI], 1.73‒not reached) on strata I and 21.6 months (95 percent CI, 4.1‒72.7) on strata II. The median progression-free survival was 18.1 months (95 percent CI, 1.73‒not reached) on strata I and 8.9 months (95 percent CI, 2.7‒24.4) on strata II.

“TMI 900 cGy, fludarabine, and melphalan are considered feasible as conditioning for allogeneic stem cell transplantation and may warrant further investigation due to favourable response rates and survival,” the investigators said.