Case Report: CAR-T cells and subsequent maintenance with ponatinib in an adult Philadelphia acute lymphoblastic leukemia patient with hematological and extramedullary relapse after allogeneic stem cell transplantation.

Relapsed or refractory (r/r) Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) still represent an unmet clinical need despite the new immune therapies available for these patients. We report the case of a Ph + ALL relapsed one year after allogeneic stem cell transplant. After one DLI was started CAR-T program with brexucabtageneautoleucel, using as bridging treatment ponatinib, vincristine and prednisone. Brexu-cel infusion was performed in 2023, without CRS or ICANS onset. One month after Brexu-cel infusion BM aspirate and CT-PET showed recovery of full donor chimerism, MRD negativity and complete metabolic remission. Subsequently was started maintenance with ponatinib: at last follow-up, the patient persisted in leukemia-free status. CAR-T cells represent the most powerful treatment for r/r Ph + ALL but there is no consensus about the optimal bridging strategy and also regarding the management algorithm during "post CAR-T phase". Here, we report the efficacy of ponatinib as a bridge to anti-CD19 CAR-T cell therapy and as post CAR-T maintenance. Our experience suggests that a preserving approach with TKI associated to low-dose chemotherapy can be the optimal bridging therapy prior to CAR-T and that an "MRD-guided" and "TKI-based" maintenance strategy can represent the best choice for Ph + ALL which satisfactorily responds to CAR-T.

Optimizing maintenance therapy in acute myeloid leukemia: where do we stand in the year 2024?

INTRODUCTION: Despite the prognosis of patients affected by acute myeloid leukemia (AML) improved in the last decade, most patients relapse. Maintenance therapy after a chemotherapy approach with or without allogeneic stem cell transplantation could be a way to control the undetectable residual burden of leukemic cells. Several studies are being carried out as maintenance therapy in AML. Some critical points need to be defined, how the physician can choose among the various drugs available. AREAS COVERED: This review discusses the advances and controversies surrounding maintenance therapy for AML patients. EXPERT OPINION: Patients withFLT3-positive AML should receive midostaurin or quizartinib in the first-linesetting. For a patient initially receiving midostaurin, consider switching to sorafenib in the post-transplant setting. Because of the improved safety profile and potency, many experts will lean toward using a second-generation FLT3 inhibitor such as quizartinib or gilteritinib. Finally, no data indicate whether maintenance therapy should be prolonged until progression or for a defined period.

First-Line Use of Daratumumab in Patients with Multiple Myeloma Shows Delayed Neutrophil and Platelet Engraftment after Autologous Stem Cell Transplantation: Results from a Real-Life Single-Center Study.

BACKGROUND: This real-life study aimed to investigate the possible impact of D-VTd induction therapy on hematopoietic engraftment after autologous stem cell transplantation (auto-SCT). METHODS: Sixty consecutive NDMM patients received four cycles of induction therapy with D-VTd. The conditioning regimen consisted of melphalan 200 mg/m2. These patients were compared with a historical control group of 80 patients who received four cycles of VTd as induction therapy. RESULTS: The median days to reach neutrophil and platelet engraftment significantly differed between patients treated with D-VTd (11 and 13 days, respectively) and VTd (10 and 12 days). Univariate Cox analyses show that patients treated with D-VTd had a hazard ratio of neutrophil engraftment that was 42% significantly lower than those in the VTd arm (HR: 0.58, p = 0.002), and a multivariate model confirmed this result. Patients treated with D-VTd developed FN more frequently. Univariate and multivariate logistic regressions revealed an association between D-VTd and FN. Delayed engraftment did not correlate with more extended hospitalization. No patients died in the first six months after transplantation. CONCLUSIONS: Our real-life study showed that a four-drug induction therapy containing DARA does not impact transplant safety outcomes.

Integrating CAR-T cell therapy into the management of DLBCL: what we are learning.

INTRODUCTION: Chimeric Antigen Receptor ;(CAR) T cells therapies have become part of the standard of care for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). The weakness of CAR-T therapies is that there are no comparative clinical trials, although many publications based on real-life data have confirmed the results obtained in pivotal studies. After several years of the commercialization of CAR-T, some points still need to be fully clarified. Healthcare professionals have questions about identifying patients who may benefit from therapy. There are aspects inherent in the accessibility of care related to improved relationships between CAR-T-delivering and referral centers. AREAS COVERED: Open questions are inherent in the salvage and bridge therapy, predictive criteria for response and persistence of CAR-T after infusion. Managing toxicities remain a top priority and one of the points on which further knowledge is needed. EXPERT OPINION: This review aims to describe the current landscape of CAR-T cells in DLBCL, outline their outcomes and toxicities, and explain the outstanding questions that remain to be addressed.

The Role of MicroRNA in Graft-Versus-Host-Disease: A Review.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a clinically challenging modality for the treatment of many hematologic diseases such as leukemia, lymphoma, and myeloma. Graft-versus-host disease (GVHD) is a common complication after allo-HSCT and remains a major cause of morbidity and mortality, limiting the success of a potentially curative transplant. Several microRNAs (miRNAs) have recently been shown to impact the biology of GVHD. They are molecular regulators involved in numerous processes during T-cell development, homeostasis, and activation, and contribute to the pathological function of T-cells during GvHD. Here, we review the key role of miRNAs contributing to the GvHD; their detection might be an interesting possibility in the early diagnosis and monitoring of disease.