Robert J. Kreitman, MD, discusses the long-term findings from the pivotal phase III trial with moxetumomab pasudotox in relapsed/refractory hairy cell leukemia.
Robert J. Kreitman, MD
Long-term findings from a pivotal phase III trial showed that moxetumomab pasudotox-tdfk (Lumoxiti) demonstrated deep and durable responses in patients with relapsed/refractory hairy cell leukemia, explained lead study author Robert J. Kreitman, MD.
At a median follow-up of 16.7 months, initial findings from the trial showed a 30% durable complete remission (CR) rate, and a 34% CR rate with minimal residual disease (MRD) negativity; both response rates were determined by blinded independent central review.1
These data served as the basis for the September 2018 FDA approval of the CD22-directed recombinant immunotoxin for the treatment of patients with relapsed/refractory hairy cell leukemia who have received ≥2 prior lines of therapy, including a purine analog.
At a median follow-up of 24.6 months, the durable CR rate increased to 36.3% (95% CI, 25.8-47.8), and the 1-year CR rate with hematologic remission was 32.5% (95% CI, 22.4-43.9). All patients who achieved an MRD-negative CR in the initial analysis remained in an MRD-negative CR after completing the full 6 cycles of therapy.2
"Moxetumomab pasudotox is really the only nonchemotherapy regimen that can be used to eliminate MRD in the majority of patients with hairy cell leukemia," said Kreitman.
The agent also demonstrated a manageable safety profile with no indication of decreased renal function over time.
Following these results, investigators launched a phase I trial (NCT03805932) of moxetumomab pasudotox in combination with rituximab (Rituxan) in the frontline setting that is currently enrolling.
In an interview with OncLive, Kreitman, senior investigator and head of the Clinical Immunotherapy Section in the Laboratory of Molecular Biology at the National Cancer Institute, discussed the long-term findings from the pivotal phase III trial with moxetumomab pasudotox in relapsed/refractory hairy cell leukemia.
OncLive: What is the role of moxetumomab pasudotox in hairy cell leukemia?
Kreitman: Purine analogs are very effective in hairy cell leukemia the first time around, but the more you use them, the less benefit they provide. They also have accumulating toxicities. After a while, patients develop purine analog-refractory hairy cell leukemia. Other targeted therapies don’t get really rid of MRD, so they generally have to be used chronically, and sometimes that's not possible.
There really is an unmet need for [these patients]. We had tested moxetumomab pasudotox in a phase I trial. We know from the phase I trial, that if you don't eliminate these traces of hairy cells, patients are going to relapse sometime in the future, especially those with multiply multiple relapsed disease. Data from the pivotal phase III trial were reported in 2018. The trial met its endpoint, and the drug was approved by the FDA. [At the 2019 ASH Annual Meeting], we presented an update of that experience showing the durability of CRs and safety of the drug.
What did the initial results show? How did the updated findings compare with the initial findings?
The initial data showed that the CR rate was 41%. To get a CR, you had to have a negative bone marrow biopsy. Radiology studies had to show a resolution in [splenomegaly] or large lymph nodes.
The primary endpoint of the pivotal trial was the 6-month durability of response, so patients’ blood counts had to stay resolved for at least 6 months. The update showed that the number of [patients who experience] durable CRs is even higher. [The primary endpoint showed an increase] in the percentage of patients who have durable CRs from around 30% to 36.3%. [Now we know], there are patients who experience CRs [after having stopped] treatment.
We also reported that the percentage of patients who were in CR followed by at least 1 year of good counts was 32.5%. Those were the major findings from an efficacy standpoint.
From a safety standpoint, we found that patients who experienced any kind of kidney abnormality, [their] kidney function returned to normal. We did not see abnormal average creatinine [levels] for a period of more than 1 year.
Could moving moxetumomab pasudotox earlier on in a treatment course help more patients achieve MRD?
That's something that we want to determine. We would like to evaluate moxetumomab pasudotox in combination with rituximab. There are 2 reasons for that. Newly diagnosed patients are going to have more hairy cells, bulky tumors, and bigger spleens than patients with multiply relapsed disease.
When patients are first diagnosed, they don't know that they're sick [even though] they have a larger amount of disease. Their immune system is better because they haven't been beaten up with these chemotherapy purine analogs. Therefore, to attack both issues, we’re combining moxetumomab pasudotox with rituximab. We have a clinical trial underway. We have treated 3 patients out of a planned 13 to 16. We're hoping to show that the combination is safe and more effective than moxetumomab pasudotox alone.
Rituximab can help kill more hairy cells and decrease normal B cells, thereby preventing the immune system from attacking moxetumomab pasudotox which [comes from] a bacterial source. We're hoping to move [that combination] into the frontline setting.
Moxetumomab pasudotox offers patients an FDA-approved option that [fills an unmet clinical need that had historically been met with] purine analogs since the early 1990s. That's a major step for patients with hairy cell leukemia.