Here are several abstracts selected from the proceedings of this year’s American Society of Hematology (ASH) Annual Meeting and Exposition, highlighting therapeutics in acute leukemias and myelodysplastic syndromes. For full details of these study abstracts, visit https://ash.confex.com/ash/2015/webprogram/start.html.
Abstract 6: Results of the global international prospective randomized placebo-controlled double-blind trial CALGB 10603/RATIFY [Alliance]1
Question Asked: Would the addition of midostaurin to induction and consolidation therapies followed by 1 year of maintenance improve overall survival compared with standard chemotherapy in younger (18 to 60 years) adults with acute myeloid leukemia (excluding acute promyelocytic leukemia) harboring any type of FLT3 mutation?
Abstract Conclusion: Yes. The addition of midostaurin significantly improved event-free survival and overall survival (in both uncensored and censored for transplant analyses) in patients whose blasts had a mutation in either tyrosine kinase domain or internal tandem domain (low or high FLT3 mutation burden). It is important to note that induction therapy consisted of 7 days of continuous intravenous infusion of cytarabine (200 mg/m2/d) with 3 once-daily doses of daunorubicin (60 mg/m2).
Abstract 1: Results of the multicenter randomized Graall-R 2005 trial comparing the pediatric-inspired Graall protocol to the same regimen plus rituximab (Rituxan), in patients aged 18 to 59 with newly diagnosed CD20-positive, BCR/ABL-negative B-cell precursor acute lymphocytic leukemia2
Question Asked: Would the addition of rituximab improve event-free survival of adult patients with CD20-positive (defined as expression of CD20 in more than 20% of leukemia blasts), BCR/ABL-negative, B-cell precursor acute lymphocytic leukemia?
Abstract Conclusion: Yes. The addition of rituximab prolonger event-free survival in patients treated in the rituximab arm (2-year event-free survival, 65% [95% CI, 56–75] vs 52% [95% CI, 43–63] in the control arm; hazard ratio = 0.66 [0.45–0.98]; P = .038. Of note, rituximab was administered during maintenance therapy as well.
Abstract 91: Interim results on the efficacy and safety of eltrombopag (Promacta) in inducing platelets responses in patients with low- and intermediate-1 International Prognostic Scoring System (IPSS) risk (myelodysplastic syndromes with severe thrombocytopenia) in a phase II, multicenter, prospective, placebo-controlled, single-blind study3
Question Asked: Is eltrombopag safe and active in patients with myelodysplastic syndromes who have a low- and intermediate-1 IPSS risk with severe thrombocytopenia (defined in this study as platelet count of < 30,000/L)?
Abstract Conclusion: According to these preliminary data, the drug appears to be well tolerated, effective (50% platelet response rate), and not associated with bone marrow fibrosis. Myelodysplastic syndromes disease progression occurred in 11% and 8% of the eltrombopag and placebo arms, respectively (P = not significant). Further follow-up is required to evaluate the impact on survival.
Abstract 908: Additional analyses and results of North American intergroup study SWOG S1117, a randomized phase II study in patients with higher-risk myelodysplastic syndromes and chronic myelomonocytic leukemia4
One of Three Questions Asked: What is the benefit of adding either vorinostat (Zolinza) or lenalidomide (Revlimid) to azacitidine in patients with higher-risk myelodysplastic syndromes or chronic myelomonocytic leukemia?
Abstract Conclusion: No, for higher-risk myelodysplastic syndromes; however, yes, for chronic myelomonocytic leukemia. In higher-risk patients with myelodysplastic syndromes, overall response rate and overall survival were similar for azacitidine monotherapy compared with combination arms, whereas for patients with chronic myelomonocytic leukemia, the overall response rate was significantly higher with azacitidine plus lenalidomide (63% vs 29%, P = .04), with a trend for longer response duration for combination therapies (P = .06).
Abstract 83: Results with frontline inotuzumab ozogamicin in combination with lower-intensity chemotherapy (mini-hyper-CVD [cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m2 x four doses]) with or without rituximab for older (≥ 60 years) adults with B-cell acute lymphoblastic leukemia5
Question Asked: Does the addition of inotuzumab ozogamicin, targeted nonmyelosuppressive therapy, to effective low-intensity chemotherapy improve outcomes without additional toxicity in older (60–79 years of age) adults with B-cell acute lymphoblastic leukemia?
Abstract Conclusion: According to these preliminary results, with a median follow-up of 19 months, yes. The mini-hyper-CVD (n = 34) appears to be superior to the historical hyper-CVAD with or without rituximab (n = 46) in a similar patient population (2-year overall survival, 70% and 38%, respectively). Of note: Sinusoidal obstructive syndrome was observed in 11% of patients (n = 4) who received mini-hyper-CVD and in three patients without a history of allogeneic transplant. ■
Disclosure: Dr. Abutalib reported no potential conflicts of interest.
1. Stone RM, Mandrekar S, Sanford BL, et al: The multi-kinase inhibitor midostaurin prolongs survival compared with placebo in combination with daunorubicin/cytarabine induction, high-dose C consolidation, and as maintenance therapy in newly diagnosed acute myeloid leukemia patients age 18–60 with FLT3 mutations: An international prospective randomized placebo-controlled double-blind trial (CALGB 10603/RATIFY [Alliance]). 2015 ASH Annual Meeting and Exposition. Abstract 6. Presented December 6, 2015.
2. Maury S, Chevret S, Thomas X, et al: Addition of rituximab improves the outcome of adult patients with CD20-positive, Ph-negative, B-cell precursor acute lymphoblastic leukemia: Results of the randomized Graall-R 2005 study. 2015 ASH Annual Meeting and Exposition. Abstract 1. Presented December 6, 2015.
3. Oliva EN, Santini V, Alati C, et al: Eltrombopag for the treatment of thrombocytopenia of low and intermediate-1 IPSS risk myelodysplastic syndromes: Interim results on efficacy, safety, and quality of life of an international, multicenter prospective, randomized, trial. 2015 ASH Annual Meeting and Exposition. Abstract 91. Presented December 5, 2015.
4. Sekeres MA, Othus M, List AF, et al: Additional analyses of a randomized phase II study of azacitidine combined with lenalidomide or with vorinostat vs. azacitidine monotherapy in higher-risk myelodysplastic syndromes and chronic myelomonocytic leukemia: North American Intergroup Study SWOG S1117. 2015 ASH Annual Meeting and Exposition. Abstract 908. Presented December 7, 2015.
5. Jabbour E, O’Brien S, Sasaki K, et al: Frontline inotuzumab ozogamicin in combination with low-intensity chemotherapy (mini-hyper-CVD) for older patients with acute lymphoblastic leukemia. 2015 ASH Annual Meeting and Exposition. Abstract 83. Presented December 5, 2015.
Dr. Abutalib is Assistant Director, Hematology & Bone Marrow Transplantation Service, Cancer Treatment Centers of America, Zion, Illinois.