Vyxeos Helps More Patients With AML Proceed to Transplant

After treatment with Vyxeos (CPX-351), there were more patients with acute myeloid leukemia who could proceed to transplant after treatment, compared to the traditional 7+3 chemotherapy regimen, according to an exploratory analysis presented at the 2017 BMT Tandem Meetings.

The exploratory analysis was conducted on data from a phase 3 study comparing Vyxeos with 7+3 for patients with secondary untreated AML. Overall, 34 of the 52 patients (65 percent) in the Vyxeos arm who proceeded to transplant remained alive after a median follow-up of 521 days. In the 7+3 arm, after 442 days of follow-up, 13 of 39 patients remained alive (33 percent).

From the time of transplant, the median overall survival (OS) was not reached in the Vyxeos arm versus 10.25 months for 7+3, representing a 54 percent reduction in the risk of death. Furthermore, 100 days after transplant, the rate of mortality from any cause was 53 percent lower in the Vyxeos arm versus 7+3.

"A greater proportion of patients treated with CPX-351 versus 7+3 in both age subgroups eventually went on to receive an allogeneic transplant," said Jeffrey E. Lancet, M.D., from the Moffitt Cancer Center, during the presentation. "We believe that these results may indicate CPX-351 could provide a potential bridge to successful allogeneic transplant in an otherwise poor-risk group of AML patients, keeping in mind that these results should be interpreted with caution as they do represent an exploratory analysis of a non-randomized subgroup of a larger phase 3 trial."

Vyxeos is a liposomal bound coformulation of cytarabine and daunorubicin which delivers the two medications in a 5 to 1 molar ratio. The phase 3 trial consisted of 309 patients aged 60 to 75 who were stratified evenly between each arm into groups aged 60 to 69 (198 patients) or from 70 to 75 (111 patients). Patient characteristics were well-balanced between the two arms and groups.

Findings from the full cohort of patients in the study showed a 3.61-month improvement in OS for Vyxeos versus 7+3. The complete response (CR) or CR with incomplete platelet or neutrophil recovery (CRi) rate was 47.7 percent versus 33.3 percent for Vyxeos and 7+3, respectively.

"In this phase 3 trial, CPX-351 was associated with a significantly longer median OS and higher response rates compared with 7+3 in patients over age 60 with newly diagnosed, high-risk or secondary AML," noted Lancet.

More patients in the Vyxeos arm went on to receive a stem cell transplant (34 percent versus 25 percent); however, this difference was not statistically significant. When looking at age demographics for those who received transplant, significantly more patients aged 70 to 75 years could proceed to transplant in the Vyxeos arm versus 7+3 (28.1 percent vs 11.1 percent).

Overall, in the age 60 to 69 group, there were 36 patients in the Vyxeos arm and 33 in the 7+3 arm who proceeded to transplant. In those aged 70 to 75, there were 16 in the Vyxeos arm and six in the 7+3 group. In the younger group, approximately 55 percent of patients were male and most had an ECOG performance status of 0 to 1 (94 percent). In the older age group, the population consisted more heavily of males (77 percent). AML subtypes and karyotypes were well balanced between the groups.

In the age 60 to 69 group, the median OS from the time of transplant was not reached in the Vyxeos arm versus 12.16 months with 7+3. In the aged 70 to 75 arm, the median OS was not reached with Vyxeos versus 6.64 months with 7+3.

"Overall, the survival of transplanted patients was longer in patients treated with CPX-351 versus 7+3, although in the 70 to 75 subgroup this difference did not quite reach statistical significance," noted Lancet.

Those with FLT3 mutations appeared to respond better to treatment with Vyxeos. In this population, those treated with Vyxeos (22 patients) had a CR or CRi of 68.2 percent, and 45 percent went on to receive a transplant. In the 7+3 group of FLT3-mutant AML (20 patients), the CR plus CRi rate was 25 percent and 10 percent proceeded to transplant.

"Of those patients who had a FLT3 mutation, a higher percentage achieved a CR or CRi with CPX-351 versus 7+3. Not surprisingly, probably because of this, a higher proportion of patients with FLT3 went on to transplant, if they received CPX-351 as their initial therapy," said Lancet.

The analysis looked at the safety profiles prior to transplant for those in the Vyxeos arm (52 patients) and 7+3 (38 patients). There were differences in infection and bleeding events in the Vyxeos arm that delayed recovery from myelosuppression, Lancet noted. Eighty-five percent of those in the Vyxeos arm experienced febrile neutropenia versus 71 percent of those in the 7+3 group. Additionally, the epistaxis rates were 38 percent versus 24 percent, for Vyxeos and 7+3, respectively.

The adverse events for each agent remained consistent in the 60 to 69 age group and those aged 70 to 75. "When we did the same analysis based on the age breakdown, there really was no significant difference in the safety profile for Vyxeos in the transplant patients in the different age subgroups," said Lancet.

Based on data from the full study, the FDA granted Vyxeos a breakthrough therapy designation in May 2016 as a treatment for patients with therapy-related AML or AML with myelodysplasia-related changes. Final OS data from the phase 3 study were initially presented at the 2016 ASCO Annual Meeting. The company developing the treatment, Jazz Pharmaceuticals, is working to complete a new drug application.