Safety and Efficacy of Blinatumomab in Combination with a Tyrosine Kinase Inhibitor for the Treatment of Relapsed Philadelphia Chromosome-Positive Leukemia

Assi, Rita; Kantarjian, Hagop; Short, Nicholas J.; Daver, Naval; Takahashi, Koichi; DiNardo, Courtney D.; Khouri, Rita; Burger, Jan A.; Jain, Nitin; Wierda, William G.; Chamoun, Salim; Konopleva, Marina; Jabbour, Elias

doi:10.1016/j.clml.2017.07.033

Cited by 37 publications

(50 citation statements)

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“…14 In addition, preliminary results have shown that the combination of TKIs and blinatumomab is feasible and effective in adult patients with recurrent or refractory (R/R) Ph+ ALL. 15 There are scarce studies focused on the outcome of patients with Ph+ ALL in first disease recurrence. A recently reported series from The University of Texas MD Anderson Cancer Center included 57 patients with first overt recurrence among 233 patients with Ph+ ALL who were treated with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) combined with either imatinib, dasatinib, or ponatinib, 16 and described an incidence (24%) similar to that found in the current study (22%).…”

Section: Discussionmentioning

confidence: 99%

“…A third possible approach could be the combination of a TKI and immunotherapy, but to the best of our knowledge experience with this combination is only preliminary and limited to patients with overt R/R status. 15 The possibility of performing allo-HSCT is attractive for patients with Ph+ ALL with low tumor burden at the time of first recurrence. However, all patients in the current study with first molecular recurrence had previously undergone transplantation and the majority of molecular recurrences occurred early (median time from CR to molecular recurrence of only 9.7 months), a feature that anticipates a high probability of transplantation-related mortality in the second allo-HSCT.…”

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confidence: 99%

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Incidence and outcome after first molecular versus overt recurrence in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia included in the ALL Ph08 trial from the Spanish PETHEMA Group

Ribera

García

Moreno

et al. 2019

Cancer

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Background Disease recurrence occurs in 20% to 40% of adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) who are treated with chemotherapy and tyrosine kinase inhibitors (TKIs). In the current study, the authors report the incidence, treatment, and outcome after first disease recurrence in young and older adults treated in the ALL Ph08 trial (ClinicalTrials.gov identifier NCT01491763). Methods Patients aged 18 to 55 years with de novo Ph+ ALL were treated with imatinib concurrently with standard‐dose induction and consolidation therapy followed by allogeneic hematopoietic stem cell transplantation (allo‐HSCT) when possible. In patients with first disease recurrence, the authors analyzed the type of recurrence, timing, location, presence of kinase domain mutations, type of treatment, and outcomes. Results Of the 125 patients, 28 patients (22%) developed disease recurrence before (4 patients) or after (24 patients) HSCT, with the recurrences being molecular in 11 patients (39%) and overt in 17 patients (61%). T315I was the most common mutation noted at the time of disease recurrence. Change in TKI was the most frequent treatment for patients with molecular disease recurrence whereas rescue chemotherapy and TKI change followed by second allo‐HSCT when possible were performed for the most part in patients with overt disease recurrence. A total of 20 patients (71%) achieved response. The median disease‐free survival (DFS) and overall survival (OS) were 8.5 months and 15.3 months, respectively. A trend for better DFS and OS was observed in patients with molecular recurrence compared with those with overt recurrence (median of 16.9 months vs 6.3 months [P = .05] and 28.7 months vs 11.5 months [P = .05] for DFS and OS, respectively). Conclusions Disease recurrence was frequent in young and older adults with Ph+ ALL who were treated with imatinib and chemotherapy with HSCT. Although the majority of patients responded to rescue therapy, their outcomes were poor, especially with regard to overt disease recurrence.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Incidence and outcome after first molecular versus overt recurrence in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia included in the ALL Ph08 trial from the Spanish PETHEMA Group

Ribera

García

Moreno

et al. 2019

Cancer

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“…114 We are currently evaluating a nonchemotherapy regimen of ponatinib and blinatumomab (because blinatumomab is superior to intensive chemotherapy in ALL salvage) to test whether this would be as effective as, if not superior to, a TKI-intensive chemotherapy regimen. 115 Rituximab as a single agent has no activity in ALL. Because of the high expression of CD20 on the surface of Burkitt and pre-B-ALL cells, we added rituximab (8 doses) to hyper-CVAD in Burkitt ALL and demonstrated that, compared with hyper-CVAD historic data, there was an improvement in survival.…”

Section: Acute Lymphocytic Leukemiamentioning

confidence: 99%

Toward the potential cure of leukemias in the next decade

Kantarjian

Keating

Freireich

2018

Cancer

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Historically, progress in leukemia research has been slow, but it has accelerated recently as a result of understanding the pathophysiology of leukemias and implementing more effective and targeted therapies. This review summarizes the progress across leukemia subsets and projects the potential cure of most leukemias in the next decade. Cancer 2018;124:4301-4313.APL constitutes 5% to 10% of AML cases. It is characterized by the translocation between chromosomes 15 and 17-t(15,17)(q22; q12)-and the corresponding promyelocytic leukemia/retinoic acid receptor α (PML-RARα) molecular abnormality. The discovery of daunorubicin and other anthracyclines in the 1970s was the first step toward

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“…The selection of TKI should be based on patient-related factors. Ponatinib plus blinatumomab is preferred as this combination has been shown to be highly effective in the relapsed setting [19][20][21]. Patients should be admitted for the first course to monitor for CRS.…”

Section: Acute Lymphoblastic Leukemiamentioning

confidence: 99%

Treating Leukemia in the Time of COVID-19

et al. 2020

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The coronavirus disease 2019 (COVID-19) pandemic poses several challenges to the management of patients with leukemia. The biology of each leukemia and its corresponding treatment with conventional intensive chemotherapy, with or without targeted therapies (venetoclax, FLT3 inhibitors, IDH1/2 inhibitors, Bruton's tyrosine kinase inhibitors), introduce additional layers of complexity during COVID-19 highrisk periods. The knowledge about COVID-19 is accumulating rapidly. An important distinction is the prevalence of "exposure" versus "clinical infectivity," which determine the risk versus benefit of modifying potentially highly curative therapies in leukemia. At present, the rate of clinical infection is < 1-2% worldwide. With a mortality rate of 1-5% in CO-VID-19 patients in the general population and potentially of > 30% in patients with cancer, careful consideration should be given to the risk of COVID-19 in leukemia. Instead of reducing patient access to specialized cancer centers and modifying therapies to ones with unproven curative benefit, there is more rationale for less intensive, yet effective therapies that may require fewer clinic visits or hospitalizations. Here, we offer recommendations on the optimization of leukemia management during high-risk COVID-19 periods.

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Safety and Efficacy of Blinatumomab in Combination with a Tyrosine Kinase Inhibitor for the Treatment of Relapsed Philadelphia Chromosome-Positive Leukemia

Cited by 37 publications

References 0 publications

Incidence and outcome after first molecular versus overt recurrence in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia included in the ALL Ph08 trial from the Spanish PETHEMA Group

Incidence and outcome after first molecular versus overt recurrence in patients with Philadelphia chromosome–positive acute lymphoblastic leukemia included in the ALL Ph08 trial from the Spanish PETHEMA Group

Toward the potential cure of leukemias in the next decade

Treating Leukemia in the Time of COVID-19

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