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3373 Timed Sequential Busulfan and Post-Transplantation Cyclophosphamide in Matched and Haploidentical Transplantation: Results of a Phase II Study

Program: Oral and Poster Abstracts
Session: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Poster II
Hematology Disease Topics & Pathways:
Adult, Biological, Therapies, Study Population, Clinically relevant, transplantation
Sunday, December 2, 2018, 6:00 PM-8:00 PM
Hall GH (San Diego Convention Center)

Uday Popat, MD1, Rohtesh S. Mehta, MD, MPH, MS2, Roland L. Bassett Jr.3*, Amanda L. Olson, MD4, Julianne Chen1*, Sairah Ahmed, MD2, Amin M. Alousi, MD2, Paolo Anderlini, MD5, Gheath Alatrash, DO, PhD1, Qaiser Bashir, MBBS1, Stefan O. Ciurea5, Chitra Hosing, MD1, Jin S Im, MD, PhD6, Partow Kebriaei, MD1, Issa F. Khouri1, David Marin, MD6, Yago Nieto, MD, PhD2*, Betul Oran, MD, MS7, Katy Rezvani, MD, PhD5, Muzaffar H. Qazilbash, MD 1, Elizabeth J. Shpall, MD2, Richard E Champlin, MD1 and Borje S Andersson, MD, PhD1

1The University of Texas MD Anderson Cancer Center, Houston, TX
2Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX
3Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
4Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
5Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
6The Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
7Stem Cell Transplantation and Cellular Therapy, The University of Texas, MD Anderson Cancer Center, Houston, TX

Background: Timed sequential busulfan (TSB) with fludarabine is a promising myeloablative conditioning regimen for patients undergoing matched donor transplantation. Whether this approach can be used for haploidentical transplantation using post-transplant cyclophosphamide (PTCy) GVH prophylaxis is not known. Furthermore, usefulness if any of PTCy GVH prophylaxis in matched donors receiving TSB is also not known. To address these issues, we conducted a prospective phase II study of TSB conditioning regimen with PTCy GvHD prophylxis.

Methods: Patients with hematological malignancies and adequate organ function were eligible for this study if they had 8/8 matched related or matched unrelated or a haploidentical related donor. They received a fixed dose of busulfan 80mg/m2 on day -13 and -12. Fludarabine 40mg/m2 was given on day -6 to -2 followed by busulfan dosed to achieve target area under the curve (AUC) of 20,000 ╬╝mol-min for the whole course based on pharmacokinetic studies done on day -13 and -6. Thiotepa 5mg/kg was given on day -7 to recipients of haploidentical donor. Graft-versus-host disease (GVHD) prophylaxis included cyclophosphamide 50mg/kg given on day 3 and 4 and tacrolimus. Haploidentical donor recipients and later MUD recipients received mycophenolate mofetil, in addition.

Results: Forty five patients with a median age of 48 (15-65) years were enrolled. Twenty four patients had AML or MDS, 9 CML or MPD, 5 Lymphoma, 4 Myeloma and 3 ALL. Donors were matched sibling 11, matched unrelated 18, and haploidentical 16. Disease risk index was high in 13, intermediate in 27, and low in 5 patients. Sixteen patients had comorbidity score of 3 or higher.

With a median follow up of 12 months (1-22), 1 year OS, PFS, NRM and relapse rates were 73% (60-88%), 68% (54-84%), 17% (5-29%), and 17% (5-29%) (Table), respectively. There were no graft failures. The median time to neutrophil engraftment was 16 days (13-39), and that of platelets (≥ 20K/µL) was 26 days (11-167). Day 100 grade II-IV and III-IV acute GVHD rates were 42% (27-57%) and 7% (95% CI 0-15%), respectively; 1-year chronic GVHD and extensive chronic GVHD rates were 11% (1-21%) and 8% (0-17%), respectively. One year OS in recipients of matched sib, matched unrelated and haploidentical donor were 89% (71-100%), 66% (45-95%), and 69% (49-96%) respectively and were not significantly different (P=0.31).

Conclusion: Timed sequential busulfan with PTCy results in lower incidence of severe acute and chronic gvhd and promising overall survival irrespective of donor source.

Disclosures: Bashir: Amgen: Other: Advisory board; Celgene: Research Funding; Spectrum: Other: Advisory board; Takeda: Other: Advisory board, Research Funding; KITE: Other: Advisory board. Oran: Celgene: Consultancy, Research Funding; ASTEX: Research Funding; AROG pharmaceuticals: Research Funding. Rezvani: Affirmed GmbH: Research Funding. Shpall: Affirmed GmbH: Research Funding. Champlin: Sanofi: Research Funding; Otsuka: Research Funding.

*signifies non-member of ASH