FDA Grants Orphan Drug Designation to MB-106 for Waldenstrom Macroglobulinemia Treatment


The FDA has granted orphan drug designation to MB-106, for the treatment of patients with Waldenstrom macroglobulinemia. The agent is being investigated in a phase 1/2 clinical trial.

The FDA has granted orphan drug designation to MB-106, for the treatment of patients with Waldenstrom macroglobulinemia (WM), according to a press release by Mustang Bio. Inc.1

MB-106 is chimeric antigen receptor (CAR) T-cell therapy that targeted CD20, a surface molecule embedded in the membrane, which impacts the differentiation of B-cells into plasma cells. The agent is a third-generation CAR derived from a fully human antibody developed by researchers at the Fred Hutchinson Cancer Research Center.

Recent data show that MB-106 achieved clinical responses in patients with high-risk B-NHL treated at varying dose levels. The objective response rate (ORR) was 96% in 26 patients. In the WM cohort, treatment with MB-106 also achieved a 100% complete response rate.

“We are very pleased to receive orphan drug designation from the FDA, as it is an important regulatory milestone for Mustang’s MB-106 program for the treatment of Waldenstrom macroglobulinemia, a rare B-cell non-Hodgkin lymphoma (B-NHL) with a significant unmet medical need. We look forward to dosing the first patient in our multicenter phase 1/2 clinical trial evaluating the safety and efficacy of MB-106 for relapsed or refractory B-NHL and chronic lymphocytic leukemia (CLL) under Mustang’s IND shortly, said Manuel Litchman, MD, president and chief executive officer of Mustang Bio Inc, in a press release. “In the phase 1 portion of this trial, MB-106 dose escalation will proceed in three separate arms, and Waldenstrom patients will be included in the indolent lymphoma arm in parallel with accrual of patients to the aggressive lymphoma and CLL arms,” he added.

In the phase 1/2, open-label, multicenter study (NCT05360238), approximately 287 patients aged 18 years or older with CD20-expressiong B-NHL or CLL will be enrolled. In the phase 1 portion of the study, patients with aggressive B-NHL including diffuse large B-cell lymphoma and mantle cell lymphoma as well as patients with indolent NHL like follicular lymphoma (FL), and those with CLL of small lymphocytic lymphoma (SLL) will be evaluated. Patients assessed in the phase 1 portion of the study will receive escalating doses of MB-106 according to a 3 + 3 study design. The phase 1 co primary end points are the incidence of treatment-emergent adverse events (TEAEs) in patients with relapsed or refractory CD20-positive B-NHL or CLL and determining the recommended phase 2 dose of the drug. Secondary end point for the phase 1 portion of the study included ORR, duration of response (DOR), and minimal residual disease (MRD) in patients with CLL.2

Patients assessed in the phase 2 portion of the study, patients with relapsed/refractory DLBCL, including those with MYC, BCL2, BCL6 rearrangement and primary mediastinal large B-cell lymphoma or transformed FL. In addition, patients with B-NHL subtypes that progressed after available therapy, including MCL, marginal zone lymphoma, WM, Burkitt-like lymphoma, hairy cell leukemia, and CLL/SLL will be included. The phase 2 primary end point is ORR, and the secondary end point include DOR, the incidence of TEAEs, and the total number of patients with MRD in CLL.

To be eligible for inclusion in the study, all patients must have an ECOG performance status or 1, a life expectancy of at least 16 weeks, and adequate laboratory tests, pulmonary function, and cardiac function. All patients must be capable of consenting to treatment and be able to follow the visit scheduled and other protocol requirements. For female patients or childbearing age, a negative pregnancy test is required, and patients of all genders must agree to use contraception during the study.

With an orphan drug designation, MB-106 will have be entitled to 7 years of market exclusivity for WM. The designation is intended for therapies that are safe and effective for the treatment of rare disease, like WM.1


1. Mustang Bio Announces orphan drug designation granted to MB-106, a CD20-targeted, autologous CAR T Cell therapy for the treatment of Waldenstrom macroglobulinemia. News release. Mustang Bio, Inc. June 22, 2022. Accessed June 23, 2022. https://bit.ly/3zZhB3V

2. Study to assess safety, tolerability and efficacy of mb-106 in patients with relapsed or refractory B-cell NHL or CLL. Clincaltrials.gov. Updated May 26, 2022. Accessed June 23, 2022. https://bit.ly/3QKGlm8

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