Ibrutinib Treatment of Mantle Cell Lymphoma Relapsing at Central Nervous System: A Case Report and Literature Review

Mantle cell lymphoma (MCL) accounts for about 5% of all lymphomas. Its clinical and histological features are heterogeneous. After a frequently good initial response, the disease generally and repeatedly relapses and finally the outcome is poor. Particularly severe is the prognosis of the rare occurrence of CNSi (Central Nervous System involvement). Ibrutinib, an oral inhibitor of Bruton tyrosine kinase (BTK), has shown strong activity in relapsing patients with Chronic Lymphocytic Leukemia (CLL) and MCL. Few reports are available about treatment with ibrutinib of patients presenting CNSi by lymphoproliferative diseases (LPD). In all of them, ibrutinib, at the dosage between 420 and 560 mg/day, showed an impressive effectiveness. Here we describe a case of MCL with CNS relapse showing an excellent response to ibrutinib administered at the unusual dose of 280 mg/day because of concomitant treatment of cardiological disease

Effectiveness of biosimilar pegfilgrastim in patients with lymphoma after high-dose chemotherapy and autologous stem cell transplantation: a real-life study

ObjectivesTo evaluate the efficacy of biosimilar (BIO) pegfilgrastim (PEG) in lymphoma patients after autologous stem cell transplantation (ASCT).Methods86 consecutive lymphoma patients who received BIO/PEG after ASCT were assessed. The primary endpoints of this study were the incidence of febrile neutropenia (FN) and time to neutrophil engraftment.ResultsMost patients were males (67.4%) with a median age of 48 years. FN occurred in 66 patients (76.7%), and most of the fever was grade 1-2. The median time to neutrophil engraftment was 9 days. The incidence of FN differs based on lymphoma type (p-value <0.01) and was higher in non-Hodgkin lymphoma (NHL) than in Hodgkin Lymphoma (HL). No statistical difference was found between NHL and HL regarding the time to reach the neutrophil engraftment. Hospitalization lasted from a minimum of 9 to a maximum of 34 days. The restricted mean time to discharge was 15.9 days (95%CI 14-16), without differences based on lymphoma type.ConclusionAlthough the study has the significant limitation of not being randomized and not having a control arm, it highlights the efficacy and safety of a BIO-PEG formulation in patients with Lymphoma and undergoing ASCT

Posttransplant cyclophosphamide as GVHD prophylaxis in patients receiving mismatched unrelated HCT: the PHYLOS trial

Posttransplant high-dose cyclophosphamide (PTCy) is effective in overcoming the negative impact of HLA disparity in the haploidentical setting. In light of these results, we investigated the efficacy of PTCy, in improving clinical outcomes of hematopoietic stem cell transplantation (HSCT) from a mismatched unrelated donor (MMUD) in patients with acute myeloid malignancies by reducing the incidence and severity of acute graft-versus-host disease (aGVHD). A prospective, single-arm, phase 2 study (PHYLOS) was conducted by the Gruppo Italiano Trapianto di Midollo Osseo. The ethical committees of the participating centers approved the study (EURODRACT 2017-003530-85). A total of 77 consecutive patients (acute myeloid leukemia: 64; myelodysplastic syndrome: 13) were enrolled at 26 Italian transplant centers (January 2020-November 2022). Median age of the patients was 53 (range, 19-65) years. The 100-day cumulative incidence of grades 2 to 4 aGVHD was 18.2% (95% CI, 10.6-27.6) and of grades 3 to 4 was 6.5% (95% CI, 3.1-15.1). Seventy-one patients (92%) had full-donor chimerism with complete neutrophil engraftment by day +30. One-year cumulative incidence of chronic GVHD was 13.4% (95% CI, 6.9-22.1). One-year cumulative incidence of nonrelapse mortality was 9.1% (95% CI, 4.0-16.9), and the relapse rate was 23.8% (95% CI, 14.9-33.9). One-year overall survival and graft relapse-free survival were 78.6% (95% CI, 67.4-86.3) and 55.3% (95% CI, 43.4-65.7), respectively. Our study in a homogeneous patient cohort suggests that PTCy leads to a low rate of aGVHD and improves clinical outcomes of HSCT from MMUD. This trial was registered at www.clinicaltrials.gov as #NCT03270748

Chimeric Antigen Receptor T-Cell Therapy: What We Expect Soon

The treatment landscape for hematologic malignancies has changed since the recent approval of highly effective chimeric antigen receptor T-cell therapies (CAR-T). Moreover, more than 600 active trials are currently ongoing. However, early enthusiasm should be tempered since several issues are still unsolved and represent the challenges for the coming years. The lack of initial responses and early relapse are some hurdles to be tackled. Moreover, new strategies are needed to increase the safety profile or shorten the manufacturing process during CAR-T cells therapy production. Nowadays, most clinically evaluated CAR-T cells products are derived from autologous immune cells. The use of allogeneic CAR-T cells products generated using cells from healthy donors has the potential to change the scenario and overcome many of these limitations. In addition, CAR-T cells carry a high price tag, and there is an urgent need to understand how to pay for these therapies as many of today’s current payment systems do not feature the functionality to address the reimbursement gap. Finally, the clinical experience with CAR-T cells for solid tumors has been less encouraging, and development in this setting is desirable

CART-Cell Therapy: Recent Advances and New Evidence in Multiple Myeloma

Despite the improvement in survival outcomes, multiple myeloma (MM) remains an incurable disease. Chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA) represents a new strategy for the treatment of relapsed/refractory MM (R/R). In this paper, we describe several recent advances in the field of anti-BCMA CAR T-cell therapy and MM. Currently, available data on anti-BCMA CART-cell therapy has demonstrated efficacy and manageable toxicity in heavily pretreated R/R MM patients. Despite this, the main issues remain to be addressed. First of all, a significant proportion of patients eventually relapse. The potential strategy to prevent relapse includes sequential or combined infusion with CAR T-cells against targets other than BCMA, CAR T-cells with novel dual-targeting vector design, and BCMA expression upregulation. Another dark side of CART therapy is safety. Cytokine release syndrome (CRS) andneurologic toxicity are well-described adverse effects. In the MM trials, most CRS events tended to be grade 1 or 2, with fewer patients experiencing grade 3 or higher. Another critical point is the extended timeline of the manufacturing process. Allo-CARs offers the potential for scalable manufacturing for on-demand treatment with shorter waiting days. Another issue is undoubtedly going to be access to this therapy. Currently, only a few academic centers can perform these procedures. Recognizing these issues, the excellent response with BCMA-targeted CAR T-cell therapy makes it a treatment strategy of great promise.</jats:p