CPX-351 prolongs OS compared with 7 + 3 chemotherapy in AML with myelodysplasia-related changes
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ORLANDO — CPX-351 extended OS compared with 7 + 3 chemotherapy among patients with acute myeloid leukemia and myelodysplasia-related changes who achieved complete remission or complete remission with incomplete neutrophil or platelet recovery, according to an exploratory subgroup analysis of a phase 3 study presented at TCT | Transplantation & Cellular Therapy Meetings.
“The longer OS with CPX-351 in this subgroup suggests potentially deeper responses may be achieved with [this treatment],” Stefan Faderl, MD, executive medical director of clinical development in hematology and oncology at Jazz Pharmaceuticals, said during a presentation.
CPX-351 (Vyxeos, Jazz Pharmaceuticals), a liposomal preparation of cytarabine and daunorubicin at synergistic ratio, received FDA approval for treatment of adults with untreated, therapy-related AML or AML with myelodysplasia-related changes.
Results of the phase 3 trial showed CPX-351 significantly prolonged median OS compared with standard 7 + 3 chemotherapy among 309 patients aged 60 to 75 years with newly diagnosed high-risk/secondary AML.
Faderl and colleagues analyzed 246 patients enrolled in the trial who were diagnosed with AML with myelodysplasia-related changes. Half of these patients (n = 123) had been randomly assigned to one to two induction cycles of CPX-351 at 100 units/m2 (100 mg/m2 cytarabine plus 44 mg/m2 daunorubicin) on days 1, 3 and 5 as a 90-minute infusion, with second induction on days 1 and 3. The other half (n = 123) received 7 + 3 chemotherapy, consisting of 100 mg/m2 cytarabine daily through continuous infusion for 7 days, with second induction for 5 days, and 60 mg/m2 daunorubicin on days 1 to 3, with second induction on days 1 and 2.
Patients who achieved complete remission or complete remission with incomplete neutrophil or platelet recovery could receive as many as two consolidation cycles with CPX-351 or 5 + 2 chemotherapy. Patients also could receive HSCT at the discretion of their physician.
Results of the subgroup analysis showed 48% of patients who received CPX-351 achieved complete remission or complete remission with incomplete neutrophil or platelet recovery, compared with 33% who received 7 + 3 chemotherapy (OR = 1.83; 95% CI, 1.09-3.09).
Median OS was superior in the CPX-351 group compared with the 7 + 3 group among patients who achieved complete remission with or without neutrophil or platelet recovery (19.15 months vs. 11.58 months).
Patients who received CPX-351 vs. 7 + 3 chemotherapy and achieved complete remission with or without neutrophil or platelet recovery also had a higher HSCT rate (54% vs. 43%; RR = 1.18; 95% CI, 0.79-1.76).
OS landmarked from the transplant date also was longer in the CPX-351 group.
Safety profiles appeared similar in both groups.
“The safety profile of CPX-351 in this subgroup was consistent with that of the overall study population and the known safety profile of 7 + 3,” Faderl said. “These results may suggest better remissions following CPX-351, with the caveat that data on minimal residual disease from these patients [are] not available.”– by John DeRosier
Reference:
Ryan D, et al. Abstract 9. Presented at: TCT | Transplantation & Cellular Therapy Meetings; Feb. 19-23, 2020; Orlando.
Disclosures: Faderl reports employment with and stock ownership in Jazz Pharmaceuticals. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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Bart Scott, MD
The HR crossed over 1 in the post-transplant setting, so you can’t really say there is a benefit with CPX-351 because it’s not significantly different.
If you go into transplant in complete remission, there was no significant difference between the two treatments. Now, if you look at the curves, it’s true that the CPX-351 curve looked better than for those who got induction chemotherapy. But we tend to believe that medicine is a science, and we try to look at it from a scientific perspective. Just because one thing is on top of another doesn’t mean it’s better. To say that something is better implies that it is statistically significant.
I believe the researchers also need to look at the molecular data. They do have the bank specimens from patients who are in complete remission, so I really encourage them to look at them to see who still has genome sequencing that is positive and who does not. If they are able to show that more patients who got CPX-351 are genome sequencing negative, that would be a very compelling story.
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