The role of ponatinib in adult BCR-ABL1 positive acute lymphoblastic leukemia after allogeneic transplantation: a real-life retrospective multicenter study

Leotta, Salvatore; Markovic, Uroš; Pirosa, Maria Cristina; Stella, Stefania; Tringali, Stefania; Martino, Massimo; Specchia, Giorgina; Carluccio, Paola; Risitano, Antonio M.; Grimaldi, Francesco; Vigna, Ernesto; Palmieri, Fausto; Palmieri, Raffaele; Annunziata, Mario; Pisapia, Giovanni; Palazzo, Giulia; Milone, Giulio Antonio; Pelle, Angelo Curto; Scalise, Luca; Giorgio, Mary Ann Di; Bulla, Anna; Leotta, Valerio; Raimondo, Francesco Di; Milone, Giuseppe

doi:10.1007/s00277-021-04504-0

Cited by 10 publications

(5 citation statements)

References 29 publications

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“…Data on post-transplant maintenance with third-generation TKIs (such as PONA) are very scarce [ 18 , 22 , 23 ]. In addition, the few studies that have been published so far included both patients transplanted with active cytologic disease and cases that were treated with PONA after Allo-SCT for a cytologic relapse [ 18 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Ponatinib as a Prophylactic or Pre-Emptive Strategy to Prevent Cytological Relapse after Allogeneic Stem Cell Transplantation in Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Transplanted in Complete Cytological Remission

Candoni,

Chiusolo,

Lazzarotto

et al. 2024

Cancers

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The administration of TKIs after Allo-SCT in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) remains controversial, and the TKI approach (prophylactic, pre-emptive or salvage) is still heterogeneous in transplant centers. In this context, very little is known about the feasibility and safety of third-generation TKIs. In this paper, we analyze the efficacy and safety of ponatinib (PONA) administered after Allo-SCT to prevent cytologic relapse of Ph + ALL. This is a multicenter observational study including 48 patients (pts) with Ph + ALL (median age 49 years) who received PONA after Allo-SCT while in complete cytological remission (cCR); 26 (54%) had positive minimal residual disease (MRD pos) before Allo-SCT. PONA was administered after Allo-SCT prophylactically (starting with MRD neg) in 26 pts or pre-emptively (starting with MRD pos post-SCT and without hematological relapse) in 22 pts. Patients treated prophylactically with PONA started treatment earlier, at a median of 4.3 months (range 1.5–6) after Allo-SCT, than those treated pre-emptively, who started PONA at a median of 7.4 months (range 2–63) after Allo-SCT (p = 0.01). The median starting dose of PONA was 30 mg/day (range 15–45). A dose reduction was required in 10/48 (21%) of cases, but a permanent discontinuation of PONA, due to toxicity, was required in only 5/48 pts (10.5%). No deaths due to PONA-related adverse events (AEs) were reported. The median follow-up time after Allo-SCT was 34 months (range 7.7–118). At the last follow-up, the median duration of PONA therapy was 22 months (range 2–100). The 5-year OS and RFS after Allo-SCT were 92% and 71%, respectively. The 5-year RFS after Allo-SCT of pts who received PONA prophylaxis was 95%, and it was 57% for those who received PONA pre-emptively (log-rank p = 0.02). In conclusion, this multicenter analysis of 48 patients with Ph + ALL undergoing Allo-SCT while in CcR, although with the caution of the retrospective data, supports the feasibility of PONA maintenance strategy after Allo-SCT with a low rate of discontinuations (10.5%) due to PONA-related AE.

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Section: Discussionmentioning

confidence: 99%

Ponatinib as a Prophylactic or Pre-Emptive Strategy to Prevent Cytological Relapse after Allogeneic Stem Cell Transplantation in Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Transplanted in Complete Cytological Remission

Candoni,

Chiusolo,

Lazzarotto

et al. 2024

Cancers

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“…A single-center retrospective study showed that a better OS can be achieved through ponatinib and bridged to HSCT in Ph-positive ALL patients, 27 and another study also confirmed this conclusion. 28 Ponatinib may induce GVL effects, thus leading to long-term survival. 17 However, the phase 2 PACE trial of ponatinib in Ph-positive leukemia showed that the patients who did not undergo HSCT had a 73% 5-year overall survival, but this trial excluded CNS disease.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Efficacy and Safety of Ponatinib and Dasatinib in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia With Central Nervous System Relapse: A Retrospective Study

Zhu

Zhu²,

Miao

et al. 2023

Technol Cancer Res Treat

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Introduction Central nervous system leukemia (CNSL) is the most common extramedullary relapse site in patients with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL), with a poor prognosis and high relapse rate. Methods We characterized the clinical data of 21 Ph-positive B-ALL patients to analyze the efficacy and safety of ponatinib for patients with central nervous system relapsed Ph-positive ALL retrospectively. Results There were 11 males and 10 females in the cohort, and their median age was 45 (9-58) years old. The total CR (complete remission) rate was 90.5%. All 9 patients achieved CR in the ponatinib group, and 10 patients achieved CR in the dasatinib group (100% vs 83.3%, respectively; P = .486) and minimal residual disease-positive CR in the ponatinib group and dasatinib group (88.9% vs 58.3%, P = .178). The medium time after achieving CR was 5 and 8 weeks ( P = .047). The total median overall survival (OS) was 31.1 months, and the 3-year OS was 49.0%. The median relapse-free survival (RFS) was 31.0 months, and the 3-year RFS was 45.2%. Patients in the ponatinib group showed a significantly longer OS than those patients in the dasatinib group with (medium OS not reached vs 27.6 months, P = .045) or without (medium OS not reached vs 27.6 months, P = .039) T315I mutations. The median RFS between the ponatinib group and the dasatinib group with T315I was not reached and 16.2 months, P = .065. The median RFS between the ponatinib group and the dasatinib group without T315I was not reached and 16.2 months, P = .036. No treatment-related deaths were observed during the therapy. Conclusion (1) Ph-positive CNSL patients seemed to have a high rate of response and postinduction MRD negativity with ponatinib and dasatinib, but ponatinib seemed to show a shorter time to achieve remission than dasatinib. (2) Ponatinib maintenance treatment might show superior survival for Ph-positive CNSL patients with or without the T315I mutation. (3) Ponatinib and dasatinib seemed to be both safe for the clinical application of Ph-positive CNSL.

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“…Furthermore, up to 50% of relapses post allo-HCT are caused by the BCR-ABL T315I mutation. Thus, prophylactic or pre-emptive use of ponatinib in this setting was tested in retrospective studies showing good tolerability of 15 mg daily dosing, and efficacy in molecular response as well as long-term OS and leukemia-free survival (31,32). The use of TKIs (from all generations) after allo-HCT for patients in first CR improved OS when given as a prophylactic or preemptive regimen (33).…”

Section: The Role Of Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Novel strategies to prevent and overcome relapse after allogeneic hematopoietic cell transplantation in acute lymphoblastic leukemia

et al. 2023

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The outcome of B-cell acute lymphoblastic leukemia (B-ALL) has improved over time with the incorporation of multi-agent chemotherapy in the treatment landscape as well as the recent approval of immunotherapeutic agents allowing a larger proportion of patients to undergo allogeneic hematopoietic cell transplantation (allo-HCT) which is still considered a potential curative approach. However, relapse post-transplant is still occurring and constitutes a common cause of treatment failure in B-ALL. The present review aims to discuss the novel strategies and therapies used to prevent and overcome relapse post allo-HCT in patients with ALL, focusing on the role of tyrosine kinase inhibitors in Philadelphia chromosome positive B-ALL, the role of innovative agents such as blinatumomab and inotuzumab ozogamicin, and finally the role of cellular therapy.

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The role of ponatinib in adult BCR-ABL1 positive acute lymphoblastic leukemia after allogeneic transplantation: a real-life retrospective multicenter study

Cited by 10 publications

References 29 publications

Ponatinib as a Prophylactic or Pre-Emptive Strategy to Prevent Cytological Relapse after Allogeneic Stem Cell Transplantation in Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Transplanted in Complete Cytological Remission

Ponatinib as a Prophylactic or Pre-Emptive Strategy to Prevent Cytological Relapse after Allogeneic Stem Cell Transplantation in Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Transplanted in Complete Cytological Remission

Comparison of the Efficacy and Safety of Ponatinib and Dasatinib in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia With Central Nervous System Relapse: A Retrospective Study

Novel strategies to prevent and overcome relapse after allogeneic hematopoietic cell transplantation in acute lymphoblastic leukemia

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