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 M.; Short, Nicholas J.; Takahashi, Koichi; Garcia‐Manero, Guillermo; DiNardo, Courtney D.; Burger, Jan A.; Cortes, Jorge; Jain, Nitin; Wierda, William G.; Chamoun, S; Konopleva, Marina

doi:10.1016/j.clml.2017.08.101

Cited by 135 publications

(46 citation statements)

References 21 publications

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“…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 . The possibility of performing allo‐HSCT is attractive for patients with Ph+ ALL with low tumor burden at the time of first recurrence.…”

Section: Discussionmentioning

confidence: 99%

“…To the best of our knowledge, there is no standard approach in routine clinical practice for the treatment of first disease recurrence in patients with Ph+ ALL, and the current recommendation is to try to include these patients in clinical trials with more potent and extended‐spectrum TKIs or with immunological approaches with monoclonal antibodies or CAR T‐cell programs . 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 …”

Section: Discussionmentioning

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%

Section: Discussionmentioning

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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“…On the basis of these observations, we developed the hyper-CVAD plus ponatinib regimen, which was associated with CR and cytogenetic CR rates of 100% and with CMR rates of 75%. 115 Rituximab as a single agent has no activity in ALL. Patients in CMR were not referred for allogeneic SCT.…”

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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“…New drugs, such as monoclonal antibodies or third generation TKIs, offer new possibilities for treatment of these patients. Few clinical experiences published so far evaluate the use of these drugs in the “posttransplant” setting [19, 20]. We described the case of a patient affected by Ph’+ ALL following early relapse after a second HSCT, who was treated with a combination of IO, DLI, and ponatinib.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Molecular Remission Achieved by Antibody Anti-CD22 and Ponatinib in a Patient Affected by Ph’+ Acute Lymphoblastic Leukemia Relapsed after Second Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report

et al. 2018

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Ph’+ acute lymphoblastic leukemia (Ph’+-ALL) is an oncohematologic disorder for which allogeneic bone marrow transplantation still offers the only chance of cure. However, relapse is the main reason for treatment failure, also after hematopoietic stem cell transplantation (HSCT). New drugs, such as third generation tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, have expanded the therapeutic landscape, especially in patients who relapsed before HSCT. Very few reports, up to now, have described the use of both classes of these new agents in combination with donor lymphocyte infusions (DLI) in the setting of patients who relapsed after HSCT. We report on a young patient affected by Ph’+-ALL, who relapsed after the second HSCT and who reached molecular remission and long-term disease control by treatment with the anti-CD22 monoclonal antibody inotuzumab ozogamicin, DLI, and the 3rd generation TKI ponatinib.

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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 135 publications

References 21 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

Long-Term Molecular Remission Achieved by Antibody Anti-CD22 and Ponatinib in a Patient Affected by Ph’+ Acute Lymphoblastic Leukemia Relapsed after Second Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report

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