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1940 Prior Use of Mogamulizumab to Allogenic Hematopoietic Stem Cell Transplantation Induces Severe Acute Graft-Versus-Host Disease

Clinical Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution
Program: Oral and Poster Abstracts
Session: 722. Clinical Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Poster I
Saturday, December 5, 2015, 5:30 PM-7:30 PM
Hall A, Level 2 (Orange County Convention Center)

Takeshi Sugio, MD1*, Koji Kato, MD, PhD1, Takatoshi Aoki, MD2*, Takanori Ota, MD3*, Noriyuki Saito, MD4*, Shuro Yoshida, MD4*, Ichiro Kawano, MD4*, Hideho Henzan, MD4*, Ken Takase, MD5*, Tsuyoshi Muta, MD, PhD6*, Kohta Miyawaki, MD1*, Takahiro Shima, MD, PhD1*, Shuichiro Takashima, MD, PhD1*, Takuji Yamauchi, MD, PhD1*, Yasuo Mori, MD, PhD1*, Goichi Yoshimoto, MD, PhD1*, Kenjiro Kamezaki, MD, PhD1, Katsuto Takenaka, MD, PhD1, Tomohiko Kamimura, MD, PhD2*, Yuju Ohno, MD, PhD3*, Tetsuya Eto, MD, Ph.D4*, Ryosuke Ogawa, MD, PhD6, Hiromi Iwasaki, MD, PhD7, Toshihiro Miyamoto, MD, PhD1 and Koichi Akashi, MD, PhD1,7

1Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
2Department of Hematology, Harasanshin Hospital, Fukuoka, Japan
3Department of Internal Medicine, Kitakyushu Municipal Medical Center, Fukuoka, Japan
4Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan
5Department of Hematology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
6Department of Hematology / Oncology, Japan Community Healthcare Organization Kyushu Hospital, Kita-Kyushu, Japan
7Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan

[Introduction] Adult T-cell leukemia/lymphoma (ATL) is an aggressive peripheral T-cell lymphoma (PTCL) with a dismal prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment in ATL patients. Mogamulizumab, a humanized anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, is a novel immunotherapeutic agent, effective in treating patients with PTCL such as ATL, PTCL-not specified, and cutaneous T-cell lymphoma. However, in allo-HSCT setting, we should be careful to use mogamulizumab because CCR4 is expressed in regulatory T cells: The mogamulizumab treatment may accelerate GVHD by eradicating regulatory T cells in allo-HSCT patients. Here, we retrospectively analyzed the effect of mogamulizumab on GVHD development in ATL patients treated with mogamulizumab prior to allo-HSCT.

[Patients and Methods] Data from the Fukuoka Bone Marrow Transplantation Group were retrospectively analyzed after the approval of mogamulizumab use in Japan.

[Results] A total of 24 patients with ATL received mogamulizumab prior to allo-HSCT between April 2012 and April 2015 in our group. The median age at allo-HSCT was 58.5 years (range, 32-72). The median intervals from the last administration of mogamulizumab to allo-HSCT were 25 days (range, 9-126). The median total dose of mogamulizumab was 3 mg/kg (range, 1-8 mg/kg). After treatment with mogamulizumab, 18 patients (75%) had achieved in remission (CR in 4 patients and PR in 14) at allo-HSCT. Ten patients received unrelated bone marrow, 5 received related peripheral blood, and 9 received cord blood as stem cell sources. Eleven patients were treated with full-intensity conditioning and 13 received reduced-intensity conditioning. Graft-versus-host disease (GVHD) prophylaxis consisted of calcineurin inhibitors (cyclosporine or tacrolimus) with short-term methotrexate in 14 patients and mycophenolate mofetil in 9. The cumulative incidence (CI) of acute GVHD at 100 days was 66.6% in grade 2-4 and 33.3% in grade 3-4. The involved organs of acute GVHD were skin in 14 patients, gut in 10, and liver in 4. Among 14 patients who developed grade 2-4 acute GVHD, 5 had severe fluid retention such as pleural effusion or ascites associated with GVHD. Chronic GVHD was observed in 6 patients, and 5 of them were extensive disease. The CI of transplant-related mortality (TRM) and relapse at 1-year were 53.2% (95%CI, 29.3-72.3%) and 29.6% (95%CI, 12.6-48.9%), respectively. The leading cause of death was GVHD (n = 7). The 1-year overall survival and progression-free survival were 19.2% (95%CI, 5.7-38.8%) and 17.2% (95%CI, 4.9-35.7%), respectively.

[Discussion] Use of mogamulizumab prior to transplantation in allo-HSCT patients has a merit to decrease the burden of ATL cells. However, it was associated with an increase of TRM due to severe GVHD. Although most of ATL patients achieved better disease status at allo-HSCT through mogamulizumab and the survival rate was expected to be 50% based on the previous data, the survival in the present study was ~20%. These data suggest that mogamulizumab administered before transplantation may have retained until an early phase of post-transplantation, and the donor or host-derived regulatory T cells might be eliminated, allowing the GVHD T-cell clone to expand. Since mogalizumab is a potent anti-ATL agent, we need to develop new treatment protocols integrating mogalizumab at a suitable dose or administration timing, to minimize the unwanted GVHD development in future studies.

Disclosures: Akashi: Asahi Kasei: Research Funding , Speakers Bureau ; Shionogi: Research Funding , Speakers Bureau ; Astellas: Research Funding , Speakers Bureau ; Celgene: Research Funding , Speakers Bureau ; Chugai: Research Funding , Speakers Bureau ; Bristol-Myers Squibb: Research Funding , Speakers Bureau ; Novartis Pharma K.K.: Consultancy , Research Funding , Speakers Bureau ; Kyowa Hakko Kirin Co., Ltd.: Consultancy , Research Funding , Speakers Bureau .

*signifies non-member of ASH