Rapidly expanding treatment options improving survival in acute myeloid leukemia
ORLANDO — Treatment options in acute myeloid leukemia are changing rapidly and improving survival of young and elderly patients, according to a presenter at Community Oncology Conference.
The changes in treatment of AML model those seen in chronic myeloid leukemia in the early 2000s, with the introduction of tyrosine kinase inhibitors, and in acute lymphoblastic leukemia at the beginning of the current decade, with the introduction of dasatinib (Sprycel, Bristol-Myers Squibb) and ponatinib (Iclusig, Takeda Oncology) and anti-CD19 and anti-CD22 antibodies.
“If we take on average 100 patients and treat them with the normal ‘3 + 7’ [standard of care chemotherapy regimen], we can probably achieve a complete remission in 60% to 70% and cure 30% to 40% of the young ones who can tolerate intensive chemotherapy,” Hagop M. Kantarjian, MD, chairman of the department of leukemia at The University of Texas MD Anderson Cancer Center, told HemOnc Today. “This has been the general notion for a long time, but there are possible regimens that are better than the standard of care, particularly ones that incorporate a nucleoside analog.”
About 35% of patients with AML have FLT3 mutations. For these patients, there are now several FDA-approved FLT3 inhibitors, including midostaurin (Rydapt, Novartis) and gilteritinib (Xospata, Atellas). Sorafenib (Nexavar; Bayer, Onyx), also a FLT3 inhibitor, is approved as targeted therapy for solid tumors, but is used often in AML.
Adding FLT3 inhibitors to chemotherapy can improve survival rates by about 5% to 10%, Kantarjian said.
Another 10% to 20% of patients with AML have IDH1 or IDH2 mutations.
Two drugs that target these mutations have been approved by the FDA for patients with relapsed and refractory AML. However, Kantarjian questioned their use as single agents for these patients.
“The FDA-approved indication may not be the best treatment value of these drugs because they are very expensive. In the approved indication, as single agents, they provide limited benefits,” Kantarjian said. “They should be used with chemotherapy in the frontline and in the salvage setting. There are already studies that show we can further improve survival with the combination compared with the single agent.”
The introduction of venetoclax (Venclexta; AbbVie, Genentech), a BCL2 inhibitor, increased the complete response rate in patients to about 65% to 70%. The median survival is around 18 months, and the estimated 2-year survival rate is 40%.
“We now have a very strong building block with venetoclax that we can add to low-intensity therapy,” Kantarjian said. “There are also ongoing clinical trials of adding it to intensive chemotherapy in younger patients.”
There are other promising but still investigational approaches to treating AML. They include antibody-drug conjugates, as well as bispecific antibody constructs that target CD33 and CD123.
Another experimental form of treatment is chimeric antigen receptor T-cell therapy, which is currently approved for some patients with ALL.
However, CAR T cells have a high toxicity rate, which needs to be further investigated and reduced, Kantarjian said.
Checkpoint inhibitors are another potential treatment for patients with AML. Certain checkpoint inhibitors have been approved to treat several types of solid tumors. However, more research is needed on their use in patients with hematologic malignancies.
“[Checkpoint inhibitors] are a major breakthrough in solid tumors, and we are testing them now in leukemia,” Kantarjian said. “They are quite toxic and we are not entirely sure if they work yet. This is still quite investigational, yet exciting form of research right now.” – by John DeRosier
Kantarjian HM. What’s new and exciting in AML. Presented at: Community Oncology Conference; April 4-5, 2019; Orlando.
Disclosures: HemOnc Today could not confirm relevant financial disclosures at time of reporting.