AML treatment combo helps most trial patients reach remission
Venclexta, along with chemo, readies patients for stem cell transplant
Written by |
Treatment with the targeted therapy Venclexta (venetoclax) in combination with chemotherapy led to disease remission for most people with hard-to-treat acute myeloid leukemia (AML) in an early clinical trial, with most patients able to undergo stem cell transplant after the regimen.
“The results of the RELAX study mark a significant leap forward, as they provide us with new and effective options to better prepare patients for a life-saving stem cell transplantation,” Uwe Platzbecker, MD, the study’s co-author and medical director of Dresden University Hospital in Germany, said in a university news story.
The study, “Venetoclax plus high-dose cytarabine and mitoxantrone as salvage treatment for relapsed or refractory acute myeloid leukaemia (RELAX): a multicentre, single-arm, phase 1/2 trial,” was published in The Lancet Haematology. The work was funded by a grant from Abbvie, which markets Venclexta.
AML is an aggressive form of blood cancer. Stem cell transplant is the only approach that can cure AML, but the cancer must be well controlled for patients to undergo the procedure. For AML patients who don’t respond to initial chemotherapy, options are limited.
“If AML stops responding to conventional intensive chemotherapy or comes back, the chances of a long-term cure decrease significantly,” said study co-author Christoph Röllig, MD, head of hematology and clinical trials at University Hospital Dresden’s Medical Clinic 1.
Finding a dose that’s safe, effective
The Phase 1/2 RELAX clinical trial (NCT04330820) enrolled 55 people with AML that was relapsed or refractory, meaning the cancer had failed to respond or came back following initial chemotherapy. All of the patients were treated with Venclexta at various doses in combination with two chemotherapies, cytarabine and mitoxantrone.
The study’s main goals were to evaluate the maximum tolerated dose of Venclexta in combination with chemotherapy (that is, the highest dose that patients can take without unacceptable safety risks) and to assess how the combination affected remission rates. Results showed that the maximum tolerated dose was not reached; therefore, the researchers recommended the highest dose of Venclexta tested in the trial — 400 mg daily for 14 days — in combination with the highest chemotherapy intensity tested as the Phase 2 dose.
Seventy-five percent of patients achieved composite complete remission, meaning they didn’t show any clear signs of cancer. Some 29% achieved complete remission with normal blood cell counts, while another 45% had complete remission with incomplete hematological recovery (meaning the cancer is not detectable, but some blood tests are still abnormal).
The researchers noted that these rates compare favorably with what’s typically expected for relapsed/refractory AML patients undergoing chemotherapy, where composite complete remission rates usually total about 40%. Most patients who achieved remission went on to receive stem cell transplants.
“With the novel … combination, we increased the remission rates previously observed with conventional chemotherapy from 40 percent of patients with relapsed AML to 75 percent,” said Leo Ruhnke, MD, study co-author and senior hematologist at
As of the latest follow-up — after a median of more than two years — most patients were still alive. Data showed overall survival rates of 65% at one year and 56% at two years.
The safety profile of the Venclexta-based regimen was generally in line with what’s typical for patients undergoing chemotherapy. The most common safety issue reported was febrile neutropenia (fever accompanied by low immune cell counts). Serious side effects, most commonly pneumonia and sepsis, were also reported in some patients, including a few fatal cases.
The researchers said that overall, the safety and efficacy of the Venclexta-based regimen “appear encouraging when considered alongside published results from other intensive salvage regimens” for relapsed/refractory AML.
“The current results indicate an encouragingly good prognosis for the patients treated in the study,” said Martin Bornhäuser, MD, study co-author and director of Medical Clinic 1 at Dresden.
Venclexta is designed to inhibit BCL-2, a protein that helps cancer cells resist death. It is approved in the U.S. to help treat people aged 75 and older with newly diagnosed AML who are not considered good candidates for intensive chemotherapy. It’s also approved in the U.S. for adults with chronic lymphocytic leukemia and small lymphocytic lymphoma, two other types of blood cancer.
