2021
DOI: 10.1002/ajh.26175
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An effective chemotherapy‐free regimen of ponatinib plus venetoclax for relapsed/refractory Philadelphia chromosome‐positive acute lymphoblastic leukemia

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Cited by 22 publications
(10 citation statements)
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“…This observation is consistent with results from other studies, 25,46 suggesting that a non-BCR-ABL1dependent mechanism of resistance underlies most relapses. T315L was previously shown to confer resistance to ponatinib, 47 and it is sensitive to axitinib in vitro. 48,49 Future studies are needed to evaluate mechanisms of relapse for patients with Ph + ALL treated with ponatinib-based regimens.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…This observation is consistent with results from other studies, 25,46 suggesting that a non-BCR-ABL1dependent mechanism of resistance underlies most relapses. T315L was previously shown to confer resistance to ponatinib, 47 and it is sensitive to axitinib in vitro. 48,49 Future studies are needed to evaluate mechanisms of relapse for patients with Ph + ALL treated with ponatinib-based regimens.…”
Section: Resultsmentioning
confidence: 99%
“…46 Moreover, the combination of ponatinib, venetoclax, and dexamethasone has demonstrated early clinical efficacy in heavily pretreated patients with relapsed/refractory Ph + ALL (complete remission or complete remission with incomplete hematologic recovery in 5/6 [83%] patients who received venetoclax 800 mg). 47 Combinations of the bispecific anti-CD3/CD19 monoclonal antibody blinatumomab with TKIs (ponatinib, dasatinib, or bosutinib) have also shown efficacy in the treatment of Ph + ALL, with high rates of CMR and favorable survival outcomes. 45,48,49 Taken together, these findings suggest that combining TKIs with steroids and/or other nonchemotherapy agents may be an effective strategy to avoid chemotherapy without compromising efficacy in patients with Ph + ALL.…”
Section: Resultsmentioning
confidence: 99%
“…Several pre-clinical studies suggested that dual targeting of pro-survival BCL2 signaling and BCR-ABL with the combination of venetoclax and a TKI may have an anti-leukemic effect and prevent resistance in the Ph+ ALL setting [ 143 , 144 , 145 ]. Combination of ponatinib, venetoclax and dexamethasone (VPD regimen) was evaluated in a phase 1/2 clinical trial that enrolled 9 patients with R/R Ph+ ALL [ 146 ]. Three patients received venetoclax at the dosage of 400 mg daily and 6 patients at the dosage of 800 mg daily.…”
Section: Treatment Of Relapsed/refractory Ph+ All Patientsmentioning
confidence: 99%
“…Preclinical evidence also suggests that Ph-positive ALL is highly dependent on Bcl-2 for survival, supporting a potential role for venetoclax in this setting [44]. Initial results in nine patients from a phase I/II study of the oral combination of ponatinib, venetoclax and dexamethasone showed a CR/CRi rate of 56% and CMR rate of 44% in a heavily pretreated population of patients with relapsed/ refractory Ph-positive ALL (78% with prior ponatinib, 56% with prior blinatumomab, and 67% with prior HSCT) [45]. With a median follow-up of 13.2 months, the median OS was not reached and none of the five responding patients had relapsed.…”
Section: Other Novel Therapiesmentioning
confidence: 99%