Yttrium-90 Ibritumomab Tiuxetan Doses Calculated to Deliver up to 15 Gy to Critical Organs May Be Safely Combined With High-Dose BEAM and Autologous Transplantation in Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma

Abstract

A B S T R A C T PurposeTo determine the maximum-tolerated radiation-absorbed dose (RAD) to critical organs delivered by yttrium-90 ( 90 Y) ibritumomab tiuxetan in combination with high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy with autologous transplantation. Patients and MethodsEligible patients had relapsed or refractory CD20ϩ non-Hodgkin's lymphoma (NHL). Individualized 90 Y activities were based on dosimetry and were calculated to deliver cohort-defined RAD (1 to 17 Gy) to critical organs with three to six patients per cohort. The therapeutic dose of 90 Y ibritumomab tiuxetan was followed by high-dose BEAM and autologous transplantation. ResultsForty-four patients were treated. Thirty percent of patients had achieved less than a partial remission to their most recent therapy and would not have been eligible for autologous transplantation at most centers. The toxicity profile was similar to that associated with high-dose BEAM chemotherapy. Two dose-limiting toxicities occurred at the 17 Gy dose level, which made 15 Gy the recommended maximum-tolerated RAD. Although eight patients received at least twice the conventional dose of 0.4 mCi/kg, a weight-based strategy at 0.8 mCi/kg would have resulted in a wide range of RAD; nearly 25% of patient cases would have received 17 Gy or more, and many would have received less than 10 Gy. With a median follow-up of 33 months for all patients, the estimated 3-year progression-free and overall survivals were 43% and 60%, respectively. Conclusion Dose-escalated90 Y ibritumomab tiuxetan may be safely combined with high-dose BEAM with autologous transplantation and has the potential to be more effective than standard-dose radioimmunotherapy. Careful dosimetry is required to avoid toxicity and undertreatment.

Allogeneic hematopoietic cell transplantation for diffuse large B cell lymphoma: who, when and how?

“…Unfortunately, these studies have either been nonrandomized, or suffered from very small patient numbers, limiting their interpretation. [16][17][18] Given the negative result from the BMT CTN 0401 trial, it seems unlikely that simply adding a radio-immunotherapeutic agent to the conditioning regimen will lead to a new standard of care.…”

Dose-escalated radioimmunotherapy as part of reduced intensity conditioning for allogeneic transplantation in patients with advanced high-grade non-Hodgkin lymphoma

“…Kaplan-Meier estimated 3-year OS after HCT from MRD or URD was 20%. Kaplan-Meier estimated 3-year OS and EFS 27,28 In allogeneic HCT, so far only standard dose (15 MBq/kg (0.4 mCi/kg)) 90 Y-ibritumomab tiuxetan has been used as part of the conditioning. Shimoni et al 29 reported 12 patients with lowand high-grade NHL treated with RIT using 90 Y-ibritumomab tiuxetan followed by RIC with fludarabine/BU/melphalan.…”

Long-term follow-up of 90Y-ibritumomab-tiuxetan (90YIT) in the conditioning of autologous hematopoietic transplantation for indolent and mantle cell lymphomas in a single French center

“…These data confirm the safety of Z-BEAM conditioning regimen in this setting and correlate with the low risk of therapy-related malignancies already mentioned after RIT. 13 Overall response rate is 100% in our Z-BEAM group like that shown in prospective studies 8,9,11 and in GELA's study including 87% of FLs 6 ( Table 2). After a median follow-up of 52.7 months (range 2.4-86.6 months), 10 patients relapsed (71%) in the Z-BEAM group.…”

“…6,8,9,11 Time to absolute neutrophil count recovery was 12 days vs 10.5 day (P = 0.069) and time to platelet recovery was 12 vs 13 days (P = 0.45). One patient in the Z-BEAM group had a prolonged aplasia despite a transfused CD34 + cells count 44 × 10 6 /kg.…”