662Stratified Intense-Dose- Yttrium-90 Ibritumumab Tiuxetan (90 YIT ) with

Bendamustine+Fludarabine Nonmyeloablative Conditioning for Allogeneic

Stem Cell Transplantation in b-Cell Malignancies
Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities
Program: Oral and Poster Abstracts
Type: Oral
Session: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities:
Conditioning Regimens

Monday, December 5, 2016: 7:15 AM

Grand Hall B (Manchester Grand Hyatt San Diego)

Issa F. Khouri, MD1 , Bill Erwin, MS 2*, Alison M Gulbis, PharmD3*, Francesco Turturro, M.D. 4 , S Cheenu Kappadath,
PhD2*, Dustin Gress, MS 2*, Rosamar B Valverde 5*, Elias J. Jabbour, MD6 , Roland L Bassett Jr. 7* and Aaron Jessop, MBA,
MD8*
1 Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center,
Houston, TX
2 Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX
3 Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX
4 Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
5 Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center,

Houston
6 Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
7 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
8 Nuclear Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1483, Houston

Background: Nonmyeloablative allogeneic transplantation has the potential to induce long-term remissions in patients
with relapsed lymphoma. However, a non-intense conditioning regimen enhances the risk of early relapse. Anti-CD20
antibody radioimmunotherapy ( 90YIT) delivers radiation dose not only to the tumor cells that bind the antibody but also
to inaccessible neighboring cells as a result of the cross-fire effect. Thus, we hypothesized that the addition of
escalated 90YIT dose to the recently published bendamustine+fludarabine conditioning regimen (Khouri et al. Blood
2014) would facilitate early cytoreduction in such patients and promote improved long-term disease control by the
allogeneic graft. Organ doses from a 90YIT weight-based activity prescription (mCi/kg) vary considerably, which justifies
a dosimetry-based strategy for mCi/kg escalation.

Methods and patients: On days -22 and -14, rituximab was given at 250 mg/m2 preceding 111In ibritumumab
and 90YIT administration, respectively. Organ dosimetric assessment was performed based on serial 111In ibritumumab
whole body scanning (0, 4, 24, 72 and 144 hours) , to select from among five 90YIT mCi/kg prescriptions (0.5, 0.75, 1,
1.25 or 1.5) that would result in an estimated 10 12 Gy dose to the liver, lungs or kidneys. Organ dose was corrected
for patient-specific mass, based on a CT volume estimate times 1.03 g/cc for liver and kidneys, and a variable specific
gravity for lungs (Simon, J Clin Monit Comput, 2000). Bendamustine 130 mg/m 2 plus 30 mg/m 2 of fludarabine IV were
given daily on days -5 to - 3 prior to transplantation. Tacrolimus and mini-methotrexate (Mycophenolate mofetil in case
of cord blood transplantation) were used for GVHD prophylaxis. In addition, thymoglobulin 1 mg/kg IV was given on
days -2, and -1 in patients receiving an unrelated donor transplant.

Results: Twenty patients were studied. The median age was 58 years (range, 37-71). Lymphoma histologies included:
indolent (n=8, 40%), diffuse large cell (n=6; 30%), double-hit (n=2; 10%) and mantle cell (n= 4, 20%). The median
number of prior chemotherapies received was 4 (range, 2-7). At study entry, 8 patients (40%) were in complete
remission following salvage therapy, 7 (35%) were in partial response, and 5 (25%) had refractory disease. Six of 16
(37.5%) patients tested were PET+. Dosimetry : The most exposed organ was either liver (16 patients) or lungs (4
patients). The distribution among the five 90YIT mCi/kg prescriptions (smallest to largest) was 2, 4, 12, 1 and 1, with a
mean of 0.94 0.23 mCi/kg. If all twenty patients were treated at 1 mCi/kg (the most common prescription), the 20 Gy
limit employed for 90YIT clinical trials prior to approval would have been exceeded in only one patient for the liver (22.9
Gy) or lungs (20.9 Gy). The maximum liver and lung doses at 0.75 mCi/kg would have been 17.2 and 15.7 Gy,
respectively. Transplant outcomes: Fifteen patients (75%) received their transplants from unrelated donors (including 1
mismatched and 2 cord blood), and only 5 (25%) from HLA-compatible siblings. The median number of CD34+ cells
infused was 6.2 10 6 /kg. Neutrophil counts recovered to > 0.5 10 9 /L after a median of 12 days (range, 0-24 days).
Platelet counts recovered to > 20 10 9 /L after a median of 19 days (range, 9-30 days). By day 30, median donor
myeloid and T-cells were 100% (range, 98-100). The cumulative incidence of acute grade 2-4 GVHD and chronic
extensive GVHD were 25% (5% for acute grade 3-4) and 32%, respectively. Treatment-related mortality (TRM) rates at
day 100 and 1 year after transplantation were 0% and 10%, respectively. The 2 cord blood transplants engrafted with
100% donor cells and none had GVHD. With a median follow-up duration of 14 months (range, 3-34 months), the
overall survival and progression-free survival rates were 85% and 70%, respectively. No significant difference in survival
or TRM could be detected by age, donor type, histology, disease status, PET status or number of prior therapies.

Conclusions: Our results indicate that dose-intense 90YIT combined with fludarabine and bendamustine is a well-
tolerated nonmyeloablative allogeneic conditioning for lymphoid malignancies, with promising results of engraftment,
GVHD and survival. Our stratified 90YIT prescription results suggest that future studies with a fixed dose of 1 mCi/kg
level without dosimetry would have an acceptable radiation risk to vital organs in this setting.

Disclosures: Jabbour: ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research

Funding; Novartis: Research Funding; BMS: Consultancy.

See more of: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant
Toxicities: Conditioning Regimens
See more of: Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities
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