- Email: [email protected]
R AML) Patients Receiving Stem Cell Transplantation (SCT)
Abstracts / Biol Blood Marrow Transplant 25 (2019) S100 S289
the only factors independently predictive of higher overall mortality. Increasing age (HR=1.3, 95% 0.9-1.9 CI; p=0.13 for age 6569, and HR=1.0, 95% 0.6-1.6 CI; p=0.097 for age 70) and diagnosis (HR=0.9, 95% 0.6-1.3 CI; p=0.6 for MDS) had no significant impact on survival. Our findings suggest that most elderly patients with AML and MDS benefit from potentially curative alloHCT. Survival was worse for patients with combined high risk DRI and many comorbidities (HR DRI+ HCTCI 3). Thus, combining DRI and HCT-CI can serve as an effective pre-HCT tool to prognosticate survival after alloHCT. Age alone should not be a limiting factor in transplant decision making in otherwise eligible patients with AML and MDS.
167 Survival of Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) Patients Receiving Stem Cell Transplantation (SCT) Rajneesh Nath MD1, Vijay Reddy MD, PhD2, Anil Kapur2, Samron Gebregergish3, Laura Gurskyte3, Margarita Kulakova3, Bart Heeg3, Mark S. Berger MD2. 1 Banner MD Anderson Cancer Center, Gilbert, AZ; 2 Actinium Pharmaceuticals, New York, NY; 3 Ingress Health, Rotterdam, Netherlands Background: The prognosis of patients with R/R AML is poor. The aim of salvage therapy in R/R AML patients is to bring patients to complete response (CR) and subsequently proceed to SCT. CR rate is generally low among R/R AML patients, particularly after 2nd salvage therapy, which can be as low as 13% according to a recent large-scale retrospective analysis (Kantarjian HM et al, Cancer 2018;124(12):2534-2540). Objective: To evaluate the survival of R/R AML patients receiving SCT, we systematically reviewed survival outcomes of R/R AML patients who underwent SCT after salvage therapy and compared with outcomes of R/R AML patients who didn’t undergo SCT after salvage therapy. Evidence Acquisition: A systematic review was conducted in PubMed, Embase, Cochrane and grey literature. Studies in R/R AML patients reporting survival of both patients receiving SCT and not receiving SCT after salvage therapy were included. Results: Twenty-four studies were included. Median CR rate after salvage chemotherapy, among the included studies, was 30% (range: 3.3% - 75%). The highest value corresponds to a population with translocation (t)(8;21) (classified within the favourable prognosis group). Eligibility for proceeding to SCT varied among studies. Median SCT rate, among the included studies, was 26.6% (range: 5% - 76.3%). Median time from salvage chemotherapy to SCT ranged from 2.1 to 4.8 months. Survival of SCT and non-SCT population was compared in a non-randomized setting in all the included studies. Median OS for patients who proceeded to SCT ranged from 6.5 to 39 months, whereas for patients who were not able to proceed to SCT median OS ranged from 1.5 to 11.9 months. Significantly lower hazard ratio (HR) for SCT compared to non-SCT was also reported, with HRs ranging from 0.25 - 0.58. Additionally, 1 thru 5-year OS rate favored SCT in all studies. Furthermore, four studies evaluated OS of SCT recipients after CR or no-CR. Median OS of SCT after CR and no-CR ranged from 11.7 to 60 months and 4 to 15 months respectively. Age, blast counts, and performance status were among the significant prognostic factors of survival after salvage chemotherapy. While in some studies blast counts and white blood cell count were also significant predictors of, respectively, OS and DFS after SCT, not all studies provided information on whether patients had active disease. Conclusion: R/R AML patients who have managed to receive SCT demonstrated better survival compared to those who did not. A limitation of this review was that no randomized controlled trials comparing SCT with chemotherapies were found
S125
and patient characteristics between the SCT and non-SCT populations differed in the included studies. Novel targeted conditioning with anti-leukemia therapies may make SCT achievable, with a reduced time to transplant, and may improve outcomes in R/R AML patients.
168 The Impact of Hematopoietic Cell Transplantation (HCT) on Survival: An Exploratory Analysis of a Phase 3 Study of CPX351 Versus 7+3 in Older Patients with Newly Diagnosed, High-Risk/Secondary AML (sAML) Tara L. Lin1, Jorge E. Cortes2, Laura F. Newell MD3, Ellen K. Ritchie4, Donna E. Hogge5, Scott R. Solomon6, Gary J. Schiller7, Matthew J. Wieduwilt8, Daniel H. Ryan9, Robert J. Ryan10, Arthur C. Louie10. 1 University of Kansas Medical Center, Kansas City, KS; 2 The University of Texas MD Anderson Cancer Center, Houston, TX; 3 Oregon Health & Science University, Portland, OR; 4 Weill Cornell Medical College, New York, NY; 5 Leukemia/BMT Program of British Columbia, Vancouver, BC, Canada; 6 The Leukemia Program at Northside Hospital Cancer Center Institute, Atlanta, GA; 7 David Geffen School of Medicine/UCLA, Los Angeles, CA; 8 University of California San Diego, Moores Cancer Center, San Diego, CA; 9 University of Rochester, Rochester, NY; 10 Jazz Pharmaceuticals, Palo Alto, CA Introduction: CPX-351 (VyxeosÒ ), a dual-drug liposomal encapsulation of cytarabine (C) and daunorubicin (D) at a synergistic ratio, is approved by the FDA and EMA for adults with newly diagnosed therapy-related AML or AML with myelodysplasiarelated changes. In a phase 3 study, CPX-351 significantly improved median overall survival (OS; 9.56 vs 5.95 mo; HR = 0.69 [95% CI: 0.52-0.90]; 1-sided P = 0.003) and event-free survival (EFS; 2.53 vs 1.31 mo; HR = 0.74 [95% CI: 0.58-0.96]; 2sided P = 0.021), and produced a higher rate of complete remission (CR) or CR with incomplete platelet or neutrophil recovery (CR+CRi; 47.7% vs 33.3%; 2-sided P = 0.016) vs 7+3 in patients (pts) aged 60-75 y with newly diagnosed high-risk/sAML. The higher CR+CRi rate may contribute to a higher rate of HCT, which is a potentially curative therapy that can impact long-term survival. Objective: This exploratory analysis used a time-dependent proportional hazards model to assess the impact of CPX-351 vs 7+3 on survival independent of HCT status. Methods: Pts could receive up to 2 induction cycles of CPX351 (100 units/m2 [C 100 mg/m2 + D 44 mg/m2] on Days 1, 3, and 5 [2nd induction: Days 1 and 3]) or 7+3 (C 100 mg/m2/d continuously for 7 d [2nd induction: 5 d] + D 60 mg/m2 on Days 1-3 [2nd induction: Days 1-2]). Pts achieving CR or CRi could receive up to 2 consolidation cycles with CPX-351 (65 units/m2 [C 65 mg/m2 + D 29 mg/m2] on Days 1 and 3) or 5+2 (as in 2nd induction). HCT was performed at the physician’s discretion. Results: Baseline characteristics were balanced between arms. The HCT rate was 34.0% (n = 52) with CPX-351 and 25.0% (n = 39) with 7+3. Median time to HCT was 114.5 d with CPX351 and 113.0 d with 7+3. Median OS landmarked from the time of HCT was significantly improved with CPX-351 vs 7+3 (not reached vs 10.25 mo; HR = 0.46 [95% CI: 0.24-0.89]). When HCT was treated as a time-dependent covariate, the HRs favored CPX-351 vs 7+3 for OS and EFS (Table), suggesting CPX-351 may be associated with prolonged OS and EFS independent of HCT. The safety profile of CPX-351 was generally consistent with that of 7+3. Early mortality rates with CPX-351 and 7+3, respectively, were 5.9% and 10.6% at Day 30 and 13.7% and 21.2% at Day 60.
the only factors independently predictive of higher overall mortality. Increasing age (HR=1.3, 95% 0.9-1.9 CI; p=0.13 for age 6569, and HR=1.0, 95% 0.6-1.6 CI; p=0.097 for age 70) and diagnosis (HR=0.9, 95% 0.6-1.3 CI; p=0.6 for MDS) had no significant impact on survival. Our findings suggest that most elderly patients with AML and MDS benefit from potentially curative alloHCT. Survival was worse for patients with combined high risk DRI and many comorbidities (HR DRI+ HCTCI 3). Thus, combining DRI and HCT-CI can serve as an effective pre-HCT tool to prognosticate survival after alloHCT. Age alone should not be a limiting factor in transplant decision making in otherwise eligible patients with AML and MDS.
167 Survival of Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) Patients Receiving Stem Cell Transplantation (SCT) Rajneesh Nath MD1, Vijay Reddy MD, PhD2, Anil Kapur2, Samron Gebregergish3, Laura Gurskyte3, Margarita Kulakova3, Bart Heeg3, Mark S. Berger MD2. 1 Banner MD Anderson Cancer Center, Gilbert, AZ; 2 Actinium Pharmaceuticals, New York, NY; 3 Ingress Health, Rotterdam, Netherlands Background: The prognosis of patients with R/R AML is poor. The aim of salvage therapy in R/R AML patients is to bring patients to complete response (CR) and subsequently proceed to SCT. CR rate is generally low among R/R AML patients, particularly after 2nd salvage therapy, which can be as low as 13% according to a recent large-scale retrospective analysis (Kantarjian HM et al, Cancer 2018;124(12):2534-2540). Objective: To evaluate the survival of R/R AML patients receiving SCT, we systematically reviewed survival outcomes of R/R AML patients who underwent SCT after salvage therapy and compared with outcomes of R/R AML patients who didn’t undergo SCT after salvage therapy. Evidence Acquisition: A systematic review was conducted in PubMed, Embase, Cochrane and grey literature. Studies in R/R AML patients reporting survival of both patients receiving SCT and not receiving SCT after salvage therapy were included. Results: Twenty-four studies were included. Median CR rate after salvage chemotherapy, among the included studies, was 30% (range: 3.3% - 75%). The highest value corresponds to a population with translocation (t)(8;21) (classified within the favourable prognosis group). Eligibility for proceeding to SCT varied among studies. Median SCT rate, among the included studies, was 26.6% (range: 5% - 76.3%). Median time from salvage chemotherapy to SCT ranged from 2.1 to 4.8 months. Survival of SCT and non-SCT population was compared in a non-randomized setting in all the included studies. Median OS for patients who proceeded to SCT ranged from 6.5 to 39 months, whereas for patients who were not able to proceed to SCT median OS ranged from 1.5 to 11.9 months. Significantly lower hazard ratio (HR) for SCT compared to non-SCT was also reported, with HRs ranging from 0.25 - 0.58. Additionally, 1 thru 5-year OS rate favored SCT in all studies. Furthermore, four studies evaluated OS of SCT recipients after CR or no-CR. Median OS of SCT after CR and no-CR ranged from 11.7 to 60 months and 4 to 15 months respectively. Age, blast counts, and performance status were among the significant prognostic factors of survival after salvage chemotherapy. While in some studies blast counts and white blood cell count were also significant predictors of, respectively, OS and DFS after SCT, not all studies provided information on whether patients had active disease. Conclusion: R/R AML patients who have managed to receive SCT demonstrated better survival compared to those who did not. A limitation of this review was that no randomized controlled trials comparing SCT with chemotherapies were found
S125
and patient characteristics between the SCT and non-SCT populations differed in the included studies. Novel targeted conditioning with anti-leukemia therapies may make SCT achievable, with a reduced time to transplant, and may improve outcomes in R/R AML patients.
168 The Impact of Hematopoietic Cell Transplantation (HCT) on Survival: An Exploratory Analysis of a Phase 3 Study of CPX351 Versus 7+3 in Older Patients with Newly Diagnosed, High-Risk/Secondary AML (sAML) Tara L. Lin1, Jorge E. Cortes2, Laura F. Newell MD3, Ellen K. Ritchie4, Donna E. Hogge5, Scott R. Solomon6, Gary J. Schiller7, Matthew J. Wieduwilt8, Daniel H. Ryan9, Robert J. Ryan10, Arthur C. Louie10. 1 University of Kansas Medical Center, Kansas City, KS; 2 The University of Texas MD Anderson Cancer Center, Houston, TX; 3 Oregon Health & Science University, Portland, OR; 4 Weill Cornell Medical College, New York, NY; 5 Leukemia/BMT Program of British Columbia, Vancouver, BC, Canada; 6 The Leukemia Program at Northside Hospital Cancer Center Institute, Atlanta, GA; 7 David Geffen School of Medicine/UCLA, Los Angeles, CA; 8 University of California San Diego, Moores Cancer Center, San Diego, CA; 9 University of Rochester, Rochester, NY; 10 Jazz Pharmaceuticals, Palo Alto, CA Introduction: CPX-351 (VyxeosÒ ), a dual-drug liposomal encapsulation of cytarabine (C) and daunorubicin (D) at a synergistic ratio, is approved by the FDA and EMA for adults with newly diagnosed therapy-related AML or AML with myelodysplasiarelated changes. In a phase 3 study, CPX-351 significantly improved median overall survival (OS; 9.56 vs 5.95 mo; HR = 0.69 [95% CI: 0.52-0.90]; 1-sided P = 0.003) and event-free survival (EFS; 2.53 vs 1.31 mo; HR = 0.74 [95% CI: 0.58-0.96]; 2sided P = 0.021), and produced a higher rate of complete remission (CR) or CR with incomplete platelet or neutrophil recovery (CR+CRi; 47.7% vs 33.3%; 2-sided P = 0.016) vs 7+3 in patients (pts) aged 60-75 y with newly diagnosed high-risk/sAML. The higher CR+CRi rate may contribute to a higher rate of HCT, which is a potentially curative therapy that can impact long-term survival. Objective: This exploratory analysis used a time-dependent proportional hazards model to assess the impact of CPX-351 vs 7+3 on survival independent of HCT status. Methods: Pts could receive up to 2 induction cycles of CPX351 (100 units/m2 [C 100 mg/m2 + D 44 mg/m2] on Days 1, 3, and 5 [2nd induction: Days 1 and 3]) or 7+3 (C 100 mg/m2/d continuously for 7 d [2nd induction: 5 d] + D 60 mg/m2 on Days 1-3 [2nd induction: Days 1-2]). Pts achieving CR or CRi could receive up to 2 consolidation cycles with CPX-351 (65 units/m2 [C 65 mg/m2 + D 29 mg/m2] on Days 1 and 3) or 5+2 (as in 2nd induction). HCT was performed at the physician’s discretion. Results: Baseline characteristics were balanced between arms. The HCT rate was 34.0% (n = 52) with CPX-351 and 25.0% (n = 39) with 7+3. Median time to HCT was 114.5 d with CPX351 and 113.0 d with 7+3. Median OS landmarked from the time of HCT was significantly improved with CPX-351 vs 7+3 (not reached vs 10.25 mo; HR = 0.46 [95% CI: 0.24-0.89]). When HCT was treated as a time-dependent covariate, the HRs favored CPX-351 vs 7+3 for OS and EFS (Table), suggesting CPX-351 may be associated with prolonged OS and EFS independent of HCT. The safety profile of CPX-351 was generally consistent with that of 7+3. Early mortality rates with CPX-351 and 7+3, respectively, were 5.9% and 10.6% at Day 30 and 13.7% and 21.2% at Day 60.