Gemtuzumab ozogamicin plus venetoclax shows promise in relapsed, refractory AML
Researchers reported early evidence of anti-leukemic effect in a phase 1b study of combination gemtuzumab ozogamicin and venetoclax in relapsed or refractory acute myeloid leukemia patients in a presentation at the ASCO20 Virtual Scientific Program.
“Traditionally, relapsed or refractory AML is treated with aggressive cytotoxic chemotherapy or more recently targeted therapies, though complete responses only occur in about 30%, and toxicity can be severe,” Saad Arain, MD, from the division of hematology/oncology at University of Illinois at Chicago, told Healio. “It is crucial that we identify other drug combinations with different mechanisms of action to try to improve response rates and better serve this population.”
Using a 3+3 design, Arain and colleagues are conducting single arm, open-label dose-escalation phase 1b study of combination of venetoclax (Venclexta; AbbVie, Genentech) and gemtuzumab ozogamicin (Mylotarg, Pfizer) in relapsed or refractory patients with AML aged 18 to 75 years. Maximum tolerated dose is the primary endpoint, but the researchers are also looking at ORR, anti-leukemic activity, adverse events and estimates of RFS, EFS and OS as secondary endpoints.
In the abstract, the researchers described the induction process as a 3-day venetoclax ramp-up to the target dose of 200 mg in cohort i, 400 mg in cohort ii or 600mg in cohort iii daily for 28 days combined with 3 mg/m2 of gemtuzumab ozogamicin infused on day 1, 4 and 7.
If patients achieved complete remission/CR with incomplete hematologic recovery, they advanced to bone marrow transplant if appropriate; or, if they achieved CR/CRi or partial remission, the researchers consolidated patients with venetoclax at the prescribed dose for 28 days and gemtuzumab ozogamicin on days 1 and 4 in cycle 2, according to the poster. However, if bone marrow transplant not appropriate, then patients in CR/CRi or PR advanced to venetoclax alone as maintenance therapy in cycles 3+ until disease progression or toxicity.
“We believe that the combination of gemtuzumab ozogamicin and venetoclax will prove effective in treating patients with relapsed or refractory AML without subjecting them to the toxicities (especially cardiotoxicities) of traditional chemotherapy,” Arain said. “We expect that this combination will be well tolerated by patients.”
Currently, the study is open and has two enrolled patients, according to the poster.
When asked about the results so far, Arain told Healio no patient has had to discontinue therapy because of unacceptable toxicity. The researchers also observed evidence of anti-leukemic effect, according to Arain. They also hope dose escalation of venetoclax will cause greater anti-leukemic activity without worsening toxicity as they begin the second dosing cohort.
“The hematology community is constantly striving to find new therapeutic options for patients with relapsed or refractory AML,” Arain said. “We are hopeful that with this study will provide compelling evidence that the addition of venetoclax will increase the response rates observed with gemtuzamab, an already effective therapy for AML, improving both the length and quality of our patients' lives.”
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Arain S, et al. Abstract TPS7566. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.