CAR T-Cell Therapy MB-102 Granted FDA Orphan Drug Designation for AML


The CAR T-Cell therapy MB-102 has been granted an Orphan Drug Designation by the FDA, according to Mustang Bio, Inc, the manufacturer of the investigational treatment.

Manuel Litchman, MD

Manuel Litchman, MD, president and chief executive officer of Mustang

Manuel Litchman, MD

The CAR T-Cell therapy MB-102 has been granted an Orphan Drug Designation by the FDA, according to Mustang Bio, Inc, the manufacturer of the investigational treatment.1

MB-102, which targets CD123, previously received Orphan Drug status for the treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). The designation incentivizes the development of novel therapies for rare diseases (<200,000 US cases) or diseases for which companies are unlikely to recoup the cost of research and development.

“We are pleased that MB-102 has received Orphan Drug Designation in 2 indications, AML and BPDCN. AML most commonly occurs in senior adults, many of whom have to forgo chemotherapy due to other health conditions. MB-102 has the potential to be an important new treatment for these and other patients, and to potentially address multiple areas of high unmet medical need. We expect to initiate a multicenter phase I/II clinical trial in patients with AML, BPDCN, and high-risk myelodysplastic syndrome in the coming months,” Manuel Litchman, MD, president and chief executive officer of Mustang, said in a press release.

According to Mustang, CD123 is commonly expressed on bone marrow cells in patients with a variety of hematologic malignancies, including AML and BPDCN. The product engineers patient T cells to identify and destroy CD123-expressing tumor cells.

A phase I study (NCT02159495) being conducted at City of Hope has demonstrated safety and early signs of efficacy with MB-102 in patients with AML and BPDCN. The first-in-human, dose-escalation trial is accruing patients aged ≥12 years with a Karnofsky performance status score ≥70.

In the study, patients first receive lymphodepletion 3 to 10 days prior to CAR T cell infusion. The treating investigators determine whether patients receive cyclophosphamide (IV, 4 and/or 3 days before CAR T); fludarabine phosphate and cyclophosphamide (IV, starting 5 days before and continuing until 3 days before CAR T); or fludarabine phosphate (IV, starting 5 days before and continuing until 3 days before CAR T) and cyclophosphamide (IV, 4 and/or 3 days before CAR T).

Autologous or allogeneic CD123+ CAR T cells are infused over 15 minutes on day 0. On or after 28 days following the infusion, patients with evidence of disease who still have CD123 expression and have not had a dose-limiting toxicity are eligible to receive a second CAR T infusion. The primary outcome measures are disease response, dose-limiting toxicity, and adverse events. Secondary outcome measures include engraftment of transferred CD123+ CAR T cell, duration of response, progression-free survival, and overall survival.

Early findings from the trial were presented in November 2018 at the AACR Special Conference on Tumor Immunology and Immunotherapy.2 At the time of the presentation, 7 patients with AML and 2 with BPDCN had received MB-102.

In the AML group, patients had received a median of 4 (range, 4-10) lines of prior therapy and all had received ≥1 prior allogeneic stem cell transplant. One of the 2 patients who received a dose of 50M CAR T cells reached a morphologic leukemic-free state (MLFS) that lasted 70 days. Three months later, the patient was treated with a second infusion, and after 35 days, had achieved blast reduction from 77.9% to 0.9% (flow cytometry). Among the 5 patients treated with a dose of 200M CAR T cells, 1 patient at day 28 was in complete remission (CR) with incomplete count recovery, 1 patients reached MLFS that improved to CR at day 84, and 3 patients had stable disease.

The 2 patients with BPDCN received a dose of 100M CAR T cells, and 1 of the 2 achieved a CR. At day 28, this patient had no signs of disease in the skin and bone marrow.

Across both cohorts, the various dose levels up to 200M CAR T cells were determined to be safe, with all toxicities being manageable and reversible. There were no reported cases of grade ≥3 neurotoxicity or cytokine release syndrome. None of the treatment-related cytopenias or dose-limiting toxicities lasted for more than 12 weeks.

“There is increased expression of CD123 on AML blasts, leukemic stem cells and BPDCN cells compared to normal hematopoietic stem cells, and it is therefore a promising target for cellular immunotherapy. We remain encouraged by interim data showing MB-102’s potential to treat BPDCN and AML and continue to evaluate MB-102’s clinical benefits in our ongoing phase I clinical trial,” principal investigator Elizabeth Lihua Budde, MD, PhD, City of Hope, said in a press release at the time the data were presented at the AACR Special Conference.


  1. Mustang Bio Receives Orphan Drug Designation for MB-102 (CD123 CAR T) for the Treatment of Acute Myeloid Leukemia. Mustang Bio. Published July 24, 2019. Accessed July 24, 2019.
  2. Mustang Bio Announces Presentation of MB-102 (CD123 CAR) Safety and Efficacy Data at AACR Special Conference on Tumor Immunology and Immunotherapy. Mustang Bio. Published November 28, 2018. Accessed July 24, 2019.
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