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CPX-351 effectively provides bridge to transplantation in poor-risk AML
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SAN DIEGO — CPX-351 conferred better outcomes after allogeneic hematopoietic stem cell transplantation than standard cytarabine and daunorubicin in older patients with high-risk acute myeloid leukemia, according to results of an exploratory analysis of a phase 3 trial presented at the ASH Annual Meeting and Exposition.
Previous results from a phase 3 study showed CPX-351 (Vyxeos, Celator Pharmaceuticals) — a liposomal formulation of cytarabine and daunorubicin encapsulated at a 5:1 ratio — improved survival compared with 7 + 3 chemotherapy in older adults with secondary AML.
Jeffrey E. Lancet, MD, senior member in the department of malignant hematology at Moffitt Cancer Center, and colleagues conducted an exploratory analysis from this study to evaluate outcomes among patients who underwent allogeneic HSCT after induction treatment.
“Allogeneic transplant is part of the treatment continuum for AML, and over the years we’ve recognized that a higher percentage of patients are able to go through transplant because of the increased availability of donors, so there’s a likelihood that transplant will become a more important therapeutic option for these patients,” Lancet told HemOnc Today. “That made it important to study this group.”
The phase 3 study included 309 patients aged 60 to 75 years with newly diagnosed secondary AML who received CPX-351 induction (100 units/m2, or 100 mg/m2 cytarabine plus 44 mg/m2 daunorubicin, on days 1, 3 and 5; n = 153) or 7 + 3 induction (100 mg/m2 cytarabine daily for 7 days plus 60 mg/m2 daunorubicin on days 1, 2 and 3; n = 156).
One hundred twenty-five patients achieved a complete response or a complete response with incomplete platelet or neutrophil recovery to induction. Ninety-one patients — 52 (34%) from the CPX-351 arm and 39 (25%) from the 7 + 3 arm — underwent transplant.
Patient and clinical characteristics were comparable among these two groups, except a greater proportion of patients treated with CPX-351 than 7 + 3 were aged 70 years or older (31% vs. 15%).
Mortality rate 100 days after transplant was 53% lower in the CPX-351 arm (9.6% vs. 20.5%).
Causes of death within 100 days of transplant in patients treated with CPX-351 and 7 + 3 included refractory AML (3.8% vs. 7.7%); graft-versus-host disease (3.8% vs. 2.6%); renal, respiratory, multi-organ failure or septic shock (0% vs. 2.6% for each); or unknown (1.9% vs. 0%).
Kaplan-Meier survival analysis at the time of transplant — based on 18 deaths (of n = 52) in the CPX-351 arm and 26 events (of n = 39) in the 7 + 3 arm — showed median OS was 10.25 months (95% CI, 6.21-16.69) in the 7 + 3 arm and not reached in the CPX-351 arm (HR = 0.46; P = .0046).
Time-dependent Cox HR for OS in the CPX-351 vs. 7 + 3 arms was 0.51 (95% CI, 0.35-0.75).
These data indicate CPX-351 will likely provide treatment to a wide range of patients with AML, Lancet told HemOnc Today.
“Were always going to be battling the issue of chemotherapy ‘unfitness,’ but we also recognize that treatment in AML is very critical, in that not treating patients is always a bad idea, unless the patient is very sick or outright refuses therapy,” Lancet said. “We’re recognizing the increasing need to treat patients, and we have more agents to choose from. But, we also recognize that in AML in particular, the high-risk or secondary subset represents a significant proportion of AML — up to 40% of older adults with AML have secondary AML. That is going to be the primary target population for this drug when it gets approved, but certainly there is reason to believe it could be applicable to other settings as well, given its novel delivery mechanism.” – by Alexandra Todak
Reference:
Lancet JE, et al. Abstract 906. Presented at: ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.
Disclosure: The study was funded by Celator Pharmaceutics. Lancet reports no relevant financial disclosures. Please see the abstract for a list of all other researchers’ relevant financial disclosures.
Perspective
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Mark Levis, MD, PhD
Most of us in the field are expecting that this drug is going to make its way into real-world practice. Regulatory agencies are looking at it, and we are all really looking forward to a potentially important new drug entering our field.
Assuming this drug is approved, I think it will be used relatively quickly — certainly in the older population. We don’t know what the label will show.
What’s more intriguing is, are we going to be able to use it in younger patients? There is no question there was no difference in OS when you compared CPX-351 with 7 + 3 in younger patients. However, if I am a younger patient with AML and I have two treatments that are equally efficacious in terms of OS but one is less toxic, I’d want the less toxic one.
It will be very interesting to see how this drug ultimately is used. If you have a drug that is at least as efficacious as 7 + 3 but less toxic, can you use that to build on adding a new agent that — in the setting of the traditional 7 + 3 — would be too toxic, but with CPX-351 might be better tolerated? I think this is going to open up a whole new world for us in AML.
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