Selected Abstracts From 2015 ASH Annual Meeting: Part 2

Focus on Therapies for Acute Leukemias and Myelodysplastic Syndromes


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Here are several more abstracts selected from the proceedings of the 2015 American Society of Hematology (ASH) Annual Meeting and Exposition, highlighting therapeutics in acute leukemias and myelodysplastic syndromes. For five other top abstracts on therapies for acute leukemias and myelodysplastic syndromes from this conference, see the December 25, 2015, issue of The ASCO Post. For full details of these study abstracts, visit https://ash.confex.com/ash/2015/webprogram/start.html.

 

Abstract 81: Updated results of GIMEMA LAL 1509 total therapy protocol on overall survival, disease-free survival, and the impact of a broader genetic-based prognostic stratification of adult patients (n = 60) with BCR/ABL1-positive acute lymphoblastic leukemia (ALL)1

Question Asked: Is a chemotherapy-free induction therapy consisting of dasatinib (day 1 to day 85) and steroids (days –6 to day 31) effective in inducing complete hematologic remission and complete molecular remission (BCR/ABL1 to ABL1 ratio = 0)?

Abstract Conclusion: First, with a median follow-up of 28.4 months (range, 4.2–43.7 months), this study confirms the effectiveness of a chemotherapy-free induction in inducing complete hematologic remission in almost all adult patients with BCR/ABL1-positive ALL (97%) and complete molecular remission in a subgroup of cases. The overall survival is 58.3% (95% confidence interval [CI]: 44.4%–76.3%) at 3-years, and the disease-free survival is 48.9% (95% CI = 36.8.0%–64.9%) at the 30-month mark. Patients who achieved complete molecular remission at day 85 (end of the induction phase as defined by this study) experienced extremely promising results.

Second, this study confirms that patients harboring p210 fusion transcript (not p190 fusion transcript) may require an intensified approach, given the lower rates of complete molecular remission and the higher relapse rates with a chemotherapy-free approach.

Finally, the study provides evidence that a broader genetic characterization using single nucleotide polymorphism array analysis at diagnosis allows a more refined prognostic stratification of BCR/ABL-positive adult patients with ALL. The unfavorable impact of IKZF1 and CDKN2A/B and/or PAX5 deletions was shown to be relevant in patients harboring p190 fusion transcript—but not in a p210 fusion transcript—possibly because of the worse outcome of the latter group of patients with ALL.

Abstract 80: A multicenter phase II study using dose-intensified pegylated asparaginase (pegaspargase ­[Oncaspar]) pediatric regimen in adults (n = 110) with newly diagnosed ALL (a DFCI ALL Consortium Trial)2

Question Asked: Is pegylated asparaginase feasible as a single dose and then every 2 weeks during induction and consolidation phases, respectively?

Abstract Conclusion: Administration of pegylated asparaginase as part of induction and consolidation therapies is feasible in adults with ALL. However, the dose and schedule of pegylated asparaginase that are well tolerated in adults are lower and less frequent (pegylated asparaginase dose was decreased to 2,000 IU/m2 and every 3 weeks during the consolidation phase) than those for pediatric patients with ALL.

Abstract 796: Multicenter U.S. Intergroup study (S0805) of intensive chemotherapy plus dasatinib (Sprycel) followed by allogeneic hematopoietic cell transplant in younger adults (< 60 years; n = 93) with BCR/ABL1-positive ALL3

Question Asked: What is the impact on relapse-free survival of adding dasatinib to the hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone)/methotrexate and cytarabine regimen in younger adults with BCR/ABL1-positive ALL?

Abstract Conclusion: With a median follow-up of 26 months (range, 9–57 months), the relapse-free survival and overall survival at 12 months were 85% and 88%, respectively. The addition of dasatinib significantly improved the 1-year relapse-free survival for those who underwent allogeneic hematopoietic cell transplant in first complete remission and is associated with an improved overall survival compared with historical data prior to the introduction of tyrosine kinase inhibitors. The relapse-free survival and overall survival after allogeneic hematopoietic cell transplant were 71% and 87%, respectively, at 1 year. Dasatinib at 100 mg daily was administered for the first 14 days of each cycle. Later, the protocol was amended, and patients received dasatinib at 70 mg daily continuously from cycle 2 onward. Patients who underwent allogeneic hematopoietic cell transplant received dasatinib at 100 mg daily starting from day +100 for up to 5 years after allogeneic hematopoietic cell transplant, with dose adjustments as necessary.

Abstract 679: Complete molecular and hematologic response in adult patients (n = 45) with relapsed/refractory BCR/ABL1-positive B-precursor ALL following treatment with blinatumomab (Blincyto): Results from a phase II single-arm, multicenter study (ALCANTARA)4

Question Asked: Would the use of blinatumomb be efficacious and tolerable in patients with relapsed/refractory BCR/ABL1-positive ALL who progressed after or were intolerant to a second- or later-generation tyrosine kinase inhibitor?

Abstract Conclusion: In this study, 16 patients achieved complete response or complete response with partial hematologic recovery during the first two cycles, for a response rate of 36% (95% CI = 22%–51%). Among 16 responders, 7 patients were able to proceed to allogeneic hematopoietic cell transplant, and 14 patients achieved minimal residual disease–negative (defined as no reverse transcriptase–polymerase chain reaction amplification of BCR-ABL at a sensitivity of 105) status. The incidence of grade ≥ 3 treatment-emergent adverse events was 82%, most commonly febrile neutropenia (27%), thrombocytopenia (22%), anemia (16%), and pyrexia (11%). The majority of these patients (96%) had prior exposure to chemotherapy as well.

 

Abstract 319: Addition of sorafenib during chemotherapy phases and as maintenance in older (≥ 60 years; median age of 67 years) adults (n = 39) with FLT3-ITD–mutated acute myeloid leukemia (AML; Alliance C11001)5

Question Asked: What is the influence on 1-year overall survival of adding sorafenib to conventional chemotherapy and as maintenance for patients with FLT3-ITD–mutated AML?

Abstract Conclusion: This single-arm phase II study met its primary endpoint, demonstrating that sorafenib at 400 mg twice daily administration during induction (days 1–7), consolidation (days 1–28 × 2 cycles) and maintenance (28-day cycle × 12 cycles) phases for FLT3-ITD–mutated AML improves the survival of older adults to more than doubling the 1-year overall survival compared with historical controls (62% [95% CI = 45%–78%] vs 30%, respectively, P < .0001).

 

Late-Breaking Abstract 8: Results of a phase III randomized, multicenter study of allogeneic hematopoietic cell transplant after myeloablative conditioning or reduced-intensity conditioning in patients with myelodysplastic syndromes (n = 54) or AML (n = 218): Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 09016

Question Asked: Could myeloablative intensity of conditioning be replaced by less toxic, reduced-intensity conditioning in patients with myelodysplastic syndromes and AML who are otherwise suitable candidates to receive myeloablative conditioning regimen (18–65 years, hematopoietic cell transplant–specific comorbidity index score ≤ 4)?

Abstract Conclusion: No. This trial confirms that reduced-intensity conditioning regimens result in higher relapse rates than myeloablative conditioning regimens, with a statistically significant advantage in relapse-free survival for patients receiving myeloablative conditioning regimen. Overall survival at 18 months for patients who received myeloablative conditioning vs reduced-intensity conditioning were 77.4% (95% CI = 69.3%–83.6%) and 67.7% (95% CI = 59.1%–74.8%), respectively, based on intention-to-treat analysis. The relapses at 18 months for patients who received myeloablative conditioning vs reduced-intensity conditioning were 13.5% (95% CI = 8.3%–19.9%) and 48.3% (95% CI = 39.6%–56.4%), respectively. Relapse-free survival for patients on the reduced-intensity conditioning arm was 47.3% (95% CI = 38.7%–55.4%) vs 67.7% (95% CI = 59.0%–74.9%) on the myeloablative conditioning arm, and the difference was statistically significant (difference of 20.4%, 95% CI = 8.8%–31.9%, P < .01). ■

Disclosure: Dr. Abutalib reported no potential conflicts of interest.

References

  1. Chiaretti S, Vitale A, Elia L, et al: Multicenter total therapy Gimema LAL 1509 protocol for de novo adult Ph+ acute lymphoblastic leukemia patients: Updated results and refined genetic-based prognostic stratification. 2015 ASH Annual Meeting. Abstract 81.
  2. DeAngelo DJ, Stevenson K, Neuberg DS, et al: A multicenter phase II study using a dose intensified pegylated-asparaginase pediatric regimen in adults with untreated acute lymphoblastic leukemia: A DFCI ALL Consortium Trial. 2015 ASH Annual Meeting. Abstract 80.
  3. Ravandi F, Othus M, O’Brien S, et al: Multi-center US intergroup study of intensive chemotherapy plus dasatinib followed by allogeneic stem cell transplant in patients with Philadelphia chromosome positive acute lymphoblastic leukemia younger than 60. 2015 ASH Annual Meeting. Abstract 796.
  4. Martinelli G, Dombret H, Chevallier P, et al: Complete molecular and hematologic response in adult patients with relapsed/refractory Philadelphia chromosome-positive B-precursor acute lymphoblastic leukemia following treatment with blinatumomab: Results from a phase 2 single-arm, multicenter study (ALCANTARA). 2015 ASH Annual Meeting. Abstract 679.
  5. Uy GL, Mandrekar S, Laumann K, et al: Addition of sorafenib to chemotherapy improves the overall survival of older adults with FLT3-ITD mutated acute myeloid leukemia (Alliance C11001). 2015 ASH Annual Meeting. Abstract 319.
  6. Scott BL, Pasquini MC, Logan B, et al: Results of a phase III randomized, multi-center study of allogeneic stem cell transplantation after high versus reduced intensity conditioning in patients with myelodysplastic syndrome or acute myeloid leukemia: Blood and Marrow Transplant Clinical Trials Network 0901. 2015 ASH Annual Meeting. Abstract LBA-8.


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