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

Hodroj, Mohammad Hassan; Dalle, Iman Abou; Moukalled, Nour; Cheikh, Jean El; Mohty, Mohamad; Bazarbachi, Ali

doi:10.3389/fimmu.2023.1191912

Cited by 2 publications

(4 citation statements)

References 72 publications

(50 reference statements)

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“…Several salvage options are now available to treat cytologic relapse following Allo-SCT, including drug-conjugated monoclonal antibodies (inotuzumab), bispecific antibodies (blinatumomab), and CAR-T therapy [ 1 , 2 , 4 , 5 , 7 ]. However, the molecular target therapy with TKIs remains a significant preventive option for cytological relapse post-Allo-SCT, and the EBMT provided specific recommendations on this topic in 2016 [ 8 , 9 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that the different TKIs have distinct safety profiles, and the major extra-hematologic toxicities for first- and second-generation TKI (imatinib, dasatinib, and nilotinib) were infections, pleural effusions (dasatinib), gastrointestinal toxicity, cutaneous rash and edema. For PONA (third-generation TKI), the main concern is the cardiovascular risks [ 1 , 6 , 7 , 9 ].…”

Section: Discussionmentioning

confidence: 99%

“…Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) still has a poor prognosis, and allogeneic hematopoietic stem cell transplantation (Allo-SCT) remains an important therapeutic option, although many advances have been made in biological knowledge and therapeutic approaches of this disease [ 1 , 2 , 3 , 4 , 5 ]. The main concerns after Allo-SCT are still transplant-related mortality and leukemia relapse prevention [ 1 , 2 , 3 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…The use of tyrosine kinase inhibitors (TKIs) in the induction and consolidation phase of Ph + ALL therapy has improved clinical outcomes and is now considered a key component of the therapeutic program [ 1 , 2 , 3 , 4 , 5 ]. However, the appropriate administration of TKIs following Allo-SCT in Ph + ALL remains controversial, and the TKI approach (prophylactic, pre-emptive or salvage) is still heterogeneous across transplant centers, although the European Bone Marrow Transplantation Society (EBMT) published specific related recommendations in 2016 [ 6 , 7 , 8 ]. In this context, little is known about the efficacy and safety of third-generation TKIs after Allo-SCT [ 6 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

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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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