Robert J. Kreitman, MD, senior investigator and head of the Clinical Immunotherapy Section in the Laboratory of Molecular Biology at the National Cancer Institute, discusses ongoing research with moxetumomab pasudotox-tdfk (Lumoxiti) in patients with hairy cell leukemia (HCL).

Moxetumomab pasudotox is approved for the treatment of patients with relapsed/refractory HCL. The drug is also under investigation in combination with rituximab (Rituxan) in patients with newly diagnosed disease. Rituximab can decrease normal B cells, thereby preventing the immune system from attacking moxetumomab pasudotox, says Kreitman. As such, the addition of rituximab could potentiate the activity of moxetumomab pasudotox monotherapy.

Moreover, newly diagnosed patients also have a more robust immune system than patients with relapsed/refractory disease. The combination is under investigation in a phase II trial that has an estimated enrollment of 13 to 16 patients, says Kreitman. If the combination is shown to be safe and more effective than moxetumomab pasudotox alone, it could become a standard of care in the frontline setting.

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Dr. Kreitman on Ongoing Research With Moxetumomab Pasudotox in Hairy Cell Leukemia

Robert J. Kreitman, MD, senior investigator and head of the Clinical Immunotherapy Section in the Laboratory of Molecular Biology at the National Cancer Institute, discusses the use of moxetumomab pasudotox-tdfk (Lumoxiti) in heavily pretreated patients with relapsed/refractory hairy cell leukemia (HCL).

In September 2018, the FDA approved the CD22-directed recombinant immunotoxin for the treatment of adult patients with relapsed/refractory HCL who received ≥2 prior lines of therapy, including treatment with a purine nucleoside analog. The agent is essentially the only non-chemotherapy drug that can induce minimal residual disease (MRD) negativity in the majority of patients with HCL, says Kreitman. This is important because data from the phase I trial examining the agent demonstrated that the presence of MRD confers a higher risk of relapse.

According to long-term follow-up from the pivotal phase III Study 1053 trial presented at the 2019 ASH Annual Meeting, moxetumomab pasudotox-tdfk led to a durable complete response (CR) of 36.3%. Durable CR served as the primary end point of the trial and was defined as the achievement of a CR and maintained hematologic remission for >180 days. Moreover, 81.6% of patients who achieved a CR also achieved MRD negativity.

Dr. Kreitman on the Use of Moxetumomab Pasudotox in Hairy Cell Leukemia

Robert J. Kreitman, MD, chief of Clinical Immunotherapy Section in the Laboratory of Molecular Biology at the National Cancer Institute, discusses the association between minimal residual disease (MRD) negativity and complete remission (CR) durations in patients with hairy cell leukemia treated with moxetumomab pasudotox, in an interview during the 

2019 Hairy Cell Leukemia Foundation Annual Conference

Kreitman presented data from combining findings from a phase I and phase III clinical trial that looked at MRD negativity in patients treated with moxetumomab pasudotox. These data demonstrated that patients will have a longer duration of CR when there is no MRD positivity. Kreitman compared several different tests that looked at MRD and found that bone marrow flow cytometry was the most sensitive assay for identifying patients who have a longer CR duration and those who have a shorter duration.

While the assay can predict MRD negativity in patients with hairy cell leukemia, bone marrow biopsies can be challenging to do often in these patients. Biopsies are done several times during treatment, but it would be beneficial to determine the MRD status with each cycle of moxetumomab pasudotox, says Kreitman. Blood flow cytometry is not as sensitive in these patients, where data showed that the blood flow was positive for MRD in 1 of 41 patients assessed from the phase I and phase III trials. Overall, blood flow cytometry cannot be used to discriminate which patients will have a shorter or longer CR duration with moxetumomab pasudotox.

View more from the 2019 Hairy Cell Leukemia Foundation Annual Conference

Robert J. Kreitman, MD, discusses the association between minimal residual disease-negativity and complete remission durations in patients with hairy cell leukemia treated with moxetumomab pasudotox.

Dr. Kreitman on MRD-Negative CRs With Moxetumomab Pasudotox in Hairy Cell Leukemia

Robert J. Kreitman, MD, chief, Clinical Immunotherapy Section, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, discusses the prognosis for patients diagnosed with hairy cell leukemia (HCL).

In the early 1970s, the life span of a patient with HCL was about 4 years following diagnosis, says Kreitman. This is the prognosis for patients without effective treatment, but with effective treatment, patients tend to relapse at the point where their blood counts become low. This happens over a median period of about 15 years, Kreitman explains.

Chemotherapy after relapse is not as efficacious, and the toxicity levels are higher. Rituximab (Rituxan) and BRAF inhibitors can be used in this setting, as well as the newly-approved CD22-directed recombinant immunotoxin moxetumomab pasudotox (Lumoxiti). Moxetumomab pasudotox was approved by the FDA in September 2018 for the treatment of adult patients with relapsed or refractory HCL who have received at least 2 prior lines of therapy, including treatment with a purine nucleoside analog.

Robert J. Kreitman, MD, chief, Clinical Immunotherapy Section, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, discusses the prognosis for patients diagnosed with hairy cell leukemia.

Dr. Kreitman on the Prognosis of Hairy Cell Leukemia

Robert J. Kreitman, MD, chief, Clinical Immunotherapy Section, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, discusses the findings of moxetumomab pasudotox as a treatment for patients with relapsed/refractory hairy cell leukemia (HCL).

The first-in-class recombinant immunotoxin moxetumomab pasudotox was evaluated in a pivotal multicenter, single-arm study of patients with relapsed/refractory HCL. Responses were durable in a substantial number of patients, and the best overall response was a complete remission (CR) in 41% of patients and a CR with no minimal residual disease (MRD) in 34% of patients by blinded independent central review.

The goal was to achieve complete remission with a resolution of normal blood counts, Kreitman says, as blood counts are low in patients with HCL at baseline. Patients who were MRD-positive achieved CRs that lasted a median of 5.9 months, but investigators observed a significantly prolonged median duration of response for those who were MRD-negative by comparison, Kreitman says.

Robert J. Kreitman, MD, chief, Clinical Immunotherapy Section, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, discusses the findings of moxetumomab pasudotox as a treatment for patients with relapsed/refractory hairy cell leukemia.

Robert J. Kreitman, MD

Articles

Dr. Kreitman on Ongoing Research With Moxetumomab Pasudotox in Hairy Cell Leukemia

Dr. Kreitman on the Use of Moxetumomab Pasudotox in Hairy Cell Leukemia

Dr. Kreitman on MRD-Negative CRs With Moxetumomab Pasudotox in Hairy Cell Leukemia

Dr. Kreitman on the Prognosis of Hairy Cell Leukemia

Dr. Kreitman on Results of Moxetumomab Pasudotox in Hairy Cell Leukemia