scholarly journals FLT3 inhibitor based induction and allogeneic stem cell transplant in CR1 improves outcomes in patients with newly diagnosed AML with very low FLT3 allelic burden

2021 ◽  
Author(s):  
Musa Yilmaz ◽  
Naval Daver ◽  
Gautam Borthakur ◽  
Tapan Kadia ◽  
Courtney DiNardo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Allogeneic Stem Cell Transplant ◽  
Flt3 Inhibitor ◽  
Allelic Burden

Phase II Study of Combination of the Hypercvad Regimen with Dasatinib in the Front Line Therapy of Patients with Philadelphia Chromosome (Ph) Positive Acute Lymphoblastic Leukemia (ALL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 837-837 ◽  
Author(s):  
Farhad Ravandi ◽  
Hagop M. Kantarjian ◽  
Deborah A. Thomas ◽  
Stefan Faderl ◽  
Dan Jones ◽  
...  
Keyword(s):  
Stem Cell ◽  
Phase Ii ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Allogeneic Stem Cell Transplant ◽  
Median Response ◽  
Platelet Recovery

Abstract Abstract 837 Background: Combination therapy with cytotoxic chemotherapy and tyrosine kinase inhibitors has improved the outcome for patients with Ph+ ALL with durable remissions in some patients even without an allogeneic stem cell transplant. The dual Src and Abl inhibitor dasatinib has ∼325 times more potent in vitro kinase inhibition than imatinib against BCR-ABL with significant clinical activity in patients with imatinib-resistant lymphoid blast phase CML (CML-LB) and Ph+ ALL. Aim: To determine the efficacy and safety of combining chemotherapy with dasatinib for treating patients with Ph+ ALL. Methods: In this phase II trial, patients with newly diagnosed Ph+ ALL receive dasatinib 50 mg po bid (or 100 mg daily) for the first 14 days of each of 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate. Patients in CR continue to receive maintenance dasatinib 50 mg po bid (or 100 mg daily) and vincristine and prednisone monthly for 2 years followed by dasatinib indefinitely. Results: We have enrolled in the study 34 patients with untreated Ph+ ALL and 7 patients with 1 prior cycle of chemotherapy (before Ph+/BCR-ABL+ status was known). Patients younger than 50 years old have received a median of 6 cycles (range 2-8) and patients 50 years and older have received a median of 6 cycles (range 1-8). 20 patients are receiving maintenance in CR and two have completed the entire treatment regimen. Median age is 51 years (range 21 – 79); 22 patients were older than 50 years, Median WBC at diagnosis was 13.6 × 109/L (range, 1-276 × 109/L). 12 patients had CNS involvement at presentation. All patients are evaluable for assessment of response to induction; 39 (95%) achieved CR after first cycle or were CR at start. Two patients died before response assessment from infections. Thirty-one of 39 (79%) evaluable patients achieved cytogenetic (CG) CR after 1 cycle; 4 had a major CG response (3 had 5% and one had 15% Ph+), 2 had insufficient metaphases, and 2 are unknown (no CG exam on day 21 marrow). To date, 22 patients (56%) have achieved complete molecular remission (CMR) and another 8 (21%) have achieved a major (but not complete) molecular response (MMR) at a median of 14 weeks from initiation of treatment (range 2 – 59 weeks). Minimal residual disease assessment by flow cytometry is negative in 35 (90%) patients at a median of 3 weeks (range, 2-18 weeks). The median time to neutrophil and platelet recovery for cycle 1 is 18 and 23 days and for subsequent cycles is 15 and 20 days. Grade 3 and 4 adverse events have included bleeding (GI, GU, soft tissue and subdural hematomas)(18), pleural effusions (9), pericardial effusion (1), reversible rise in creatinine (10), deep vein thromboses (6), pulmonary emboli (3), as well as diarrhea, infections, hypophosphatemia, hypokalemia, hypocalcemia, hyperglycemia, and elevated transaminases. With a median follow up of 13 months (range 1-33), 29 patients (71%) are alive and 27 (66%) are in CR; 4 patients died in CR; 1 from an unrelated cardiac event and 3 from infections. Three patients have undergone an allogeneic stem cell transplant. The median disease free survival is 48+ weeks (range,1 to 140+) and the median overall survival is 52+ weeks (range, 3 to 143+). Eight patients have relapsed with a median response duration of 51 weeks (range 23-73) and 6 of them have died. In 5 patients morphological relapse was preceded by flow and molecular relapse. Five relapsed patients had ABL mutations (3 T315I, 1 F359V, and 1 V299L). Conclusion: Combination of chemotherapy with dasatinib is effective in achieving long term remissions in patients with newly diagnosed Ph+ ALL. Disclosures: Ravandi: Bristol Myers Squibb: Honoraria, Research Funding. Kantarjian:Bristol Myers Squibb: Research Funding. Wierda:Genzyme: Research Funding; Genentech: Consultancy, Honoraria. Cortes:Bristol Myers Squibb: Research Funding. O'Brien:Bristol Myers Squibb: Research Funding.

Final Report Of Single-Center Study Of Chemotherapy Plus Dasatinib For The Initial Treatment Of Patients With Philadelphia-Chromosome Positive Acute Lymphoblastic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3914-3914
Author(s):  
Farhad Ravandi ◽  
Susan O'Brien ◽  
Rebecca Garris ◽  
Stefan H. Faderl ◽  
Deborah A. Thomas ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Allogeneic Stem Cell Transplant

Abstract Background The dual Src and Abl inhibitor dasatinib has significant in vitro kinase inhibition against wild-type and mutant BCR-ABL, and significant clinical activity in patients with imatinib-resistant lymphoid blast phase CML (CML-LB) and Philadelphia-chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). Aim To determine the long-term efficacy of the combination of the hyperCVAD regimen with dasatinib for treating patients with Ph+ ALL. Methods In this phase II trial, patients with newly diagnosed Ph+ ALL received dasatinib 50 mg po bid (or 100 mg daily) for the first 14 days of each of 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate (induction/consolidation cycles). After 42 patients, the protocol was amended to give dasatinib 100 mg daily in the first 14 days of the first cycle and then 70 mg daily continuously from the second cycle. Patients in complete remission (CR) continued to receive maintenance dasatinib 50 mg po bid (or 100 mg daily) and vincristine and prednisone monthly for 2 years followed by dasatinib indefinitely. Patients eligible for allogeneic stem cell transplant proceeded to it in first CR. Results 63 patients with untreated Ph+ ALL and 9 patients with 1 or 2 prior cycles of chemotherapy (before Ph+/BCR-ABL+ status was known) have been enrolled in the study from September 2006 to March 2012. Patients have received a median of 6 cycles (range 1-8) of induction/consolidation. Median age is 55 years (range 21 – 80); 46 patients were older than 50 years, Median WBC at diagnosis was 12 x 109/L (range, 0.4 - 658.1 x 109/L). Ten patients had CNS involvement at presentation. All patients are evaluable for assessment of response to induction; 69 (96%) achieved CR after first cycle or were CR at start. 3 patients died before response assessment from infections. 57 of 69 (83%) evaluable patients achieved cytogenetic (CG) CR after 1 cycle; 5 had a major CG response (4 had 5% and one had 15% Ph+), 2 had insufficient metaphases, and 5 are unknown (no CG exam on day 21 marrow). To date, 45 patients (65%) have achieved complete molecular remission (CMR) and another 19 (28%) have achieved a major (but not complete) molecular response (MMR) at a median of 4 weeks from initiation of treatment (range, 2 – 38 weeks). Minimal residual disease assessment by flow cytometry is negative in 65 (94 %) patients at a median of 3 weeks (range, 2-37 weeks). The median time to neutrophil and platelet recovery for cycle 1 is 18 and 22 days and for subsequent cycles is 15 and 20 days. Grade 3 and 4 adverse events have included bleeding (GI, GU, soft tissue and subdural hematomas), pleural effusions, pericardial effusions, reversible rise in creatinine, deep vein thromboses, pulmonary emboli, as well as diarrhea, infections, hypophosphatemia, hypokalemia, hypocalcemia, hyperglycemia, and elevated transaminases. With a median follow up of 48 months in the surviving patients (range 16.5 - 81.5), 36 patients (50%) are alive and 31 (43%) are in CR. Twelve patients have undergone an allogeneic stem cell transplant. Thirty six patients have died [3 at induction, 16 after relapse, 7 post stem cell transplant performed in CR1, and 10 in CR (6 from infections, 1 from unrelated cardiac event, 1 from unrelated cancer, and 2 from an unknown cause)]. The median disease free survival is 31 months (range, 0.3 to 81) and the median overall survival is 44 months (range, 0.2 to 82). Twenty-one patients have relapsed with a median response duration of 16 months (range, 5 - 62) and 16 of them have died. In 6 patients morphological relapse was preceded by flow and molecular relapse. Six relapsed patients had ABL mutations (4 T315I, 1 F359V, and 1 V299L). Conclusion Combination of chemotherapy with dasatinib is effective in achieving long term remissions in patients with newly diagnosed Ph+ ALL. Disclosures: Ravandi: Bristol Myers Squibb: Honoraria, Research Funding. Off Label Use: Use of dasatinib for the frontline therapy of Ph+ ALL. O'Brien:Pharmacyclics: Research Funding. Jabbour:Bristol Myers Squibb: Consultancy, Honoraria. Cortes:Bristol Myers Squibb: Research Funding. Kantarjian:Bristol Myers Squibb: Research Funding.

scholarly journals GIMEMA AML1310 trial of risk-adapted, MRD-directed therapy for young adults with newly diagnosed acute myeloid leukemia

Blood ◽  
2019 ◽  
Vol 134 (12) ◽  
pp. 935-945 ◽  
Author(s):  
Adriano Venditti ◽  
Alfonso Piciocchi ◽  
Anna Candoni ◽  
Lorella Melillo ◽  
Valeria Calafiore ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Myeloid Leukemia ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Allogeneic Stem Cell Transplant ◽  
Younger Adults ◽  
Key Points ◽  
Acute Myeloid

Key Points A risk-adapted, MRD-driven transplant strategy is a feasible approach for the treatment of younger adults with AML. Pretransplant MRD positivity should not contraindicate delivery of an allogeneic stem cell transplant.

Sign in / Sign up

Export Citation Format

Share Document