Association of Peripheral Regulatory T Cells with Achievement of Deep Molecular Response in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia Treated with Dasatinib - the Final Results of D-First Study

• Published in: Blood 2016-12, Vol.128 (22), p.1916-1916
• Main Authors: Yoshida, Chikashi, Iriyama, Noriyoshi, Najima, Yuho, Fujisawa, Shin, Wakita, Hisashi, Chiba, Shigeru, Okamoto, Shinichiro, Kawakami, Kimihiro, Takezako, Naoki, Kumagai, Takashi, Ohyashiki, Kazuma, Taguchi, Jun, Yano, Shingo, Igarashi, Tadahiko, Kouzai, Yasuji, Morita, Satoshi, Sakamoto, Junichi, Sakamaki, Hisashi, Inokuchi, Koiti
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V128.22.1916.1916

Introduction Achievement of deep molecular response (DMR) has become an important treatment goal for patients with chronic phase chronic myeloid leukemia (CP-CML) since it is considered to be necessary for the challenge of stopping tyrosine kinase inhibitor (TKI) treatment. However, prognostic marker for prediction of DMR has not been established. We have previously reported the results of D-First study that shorter having time of BCR-ABL1 transcripts and early cytotoxic lymphocyte expansion were associated with achievement of DMR in newly diagnosed CP-CML patients treated with dasatinib. Here, the long-term follow-up results of the study were analyzed after a minimum 36 months follow-up. In this analysis, we mainly focus on dynamics of regulatory T cells (Treg) influencing patients' clinical course, as well as immunoprofiles during dasatinib treatment. Methods: A total of 52 patients with newly diagnosed CP-CML who were enrolled between June 2011 and June 2012 and treated with dasatinib 100 mg once daily on an open-label, multicenter, prospective phase II clinical trial (NCT01464411). All patients were followed-up for minimum of 36 months. Patients were assessed for molecular response before and 1, 3, 6, 9, 12, 15, 18, 24, and 36 months after starting dasatinib by real-time quantitative polymerase chain reaction analysis of BCR-ABL1 transcripts standardized on an international scale (BCR-ABL1 IS). A DMR was defined as less than 0.01% BCR-ABL1IS (MR4). The analysis of immunophenotyping of lymphocyte fractions in the peripheral blood samples was performed by flow cytometry before and 1, 2, 3, 6, 9, 12, 15, 18, 24, and 36 months after starting dasatinib treatment at a centralized laboratory (BML). Results: Patients’ characteristic at diagnosis has been reported previously. Briefly, the median age was 52 years. High Sokal risk score was seen in 12% patients. With a minimum follow-up of 36 months, 12 (23%) patients have discontinued therapy. Reasons for treatment discontinuation includes: pleural effusion (N=3), pericardial effusion (1), proteinurea and systemic edema (1), pulmonary hypertension (1), malaise (1), elevation of intraocular pressure (1), interstitial pneumonia (1), and patient’s requests (3). A cumulative rate of MMR was 75% by 12 months, 80% by 18 months, 86% by 24 months and 88% by 36 months. A cumulative rate of DMR was 49% by 12 months, 59% by 18 months, 59% by 24 months, and 65% by 36 months. Two patients died because of reasons unrelated to