Clinical use of immune-checkpoints inhibitors (anti PD-1/PD-L1) resulted very effective for the treatment of relapsed/refractory classic Hodgkin Lymphoma (CHL). Recently, T cell Ig and ITIM domains ...(TIGIT) has been recognized as an immune checkpoint receptor able to negatively regulate T cell functions. Herein, we investigated the expression of TIGIT in CHL microenvironment in order to find a potential new target for inhibitor therapy. TIGIT, PD-1 and PD-L1 expression was evaluated in 34 consecutive patients with CHL. TIGIT expression in T lymphocytes surrounding Hodgkin Reed-Sternberg (HRS) cells was observed in 19/34 patients (56%), of which 11 (58%) had advanced stages. In 16/19 (84%) cases, TIGIT+ peritumoral T lymphocytes showed also PD-1 expression. All 15 TIGIT- patients had PD-L1 expression in HRS cells (100%) while among 19 TIGIT+ patients, 11 (58%) were PD-L1+ and 8 (42%) were PD-L1-. Using a new scoring system for TIGIT immunoreactivity, all TIGIT+ cases with higher score (4/19) were PD-L1-. Our results confirm co-expression of TIGIT and PD-1 in peritumoral T lymphocytes. Of relevance, we demonstrated a mutually exclusive expression of TIGIT and PD-L1 using new TIGIT scoring system able to identify this immunocheckpoints' modulation. These results pave the way to new therapeutic strategies for relapsed/refractory CHL.
Cytomegalovirus (CMV) infection represents one of the main cause mortality after Stem Cell Transplantation. Recently, a protective effect of the T allele of rs12979860 IL28B Single Nucleotide ...Polymorphisms (SNPs) against CMV infection in the allogenic stem cell transplantation was suggested. We investigate whether the rs12979860 IL28B SNP and the relative rs368234815 (IFNλ4) genotype may affect the incidence of active CMV infection in Autologous stem cell transplantation (Auto-SCT) setting. The study included 99 patients who underwent to Auto-SCT. IL28 and IFNΔ4 SNPs were correlated with CMV reactivation along with other clinical and treatment parameters. CMV reactivation by CMV DNAemia was evaluated once a week until day 100 from Auto-SCT. CMV reactivation was documented in 50% (TT-ΔG/ΔG), 35% (CC-TT/TT) and 29.2% (CT-TT/ΔG) of the patients respectively. No differences in CMV copies number were recorded at reactivation between different IL28/IFNλ4 genotypes. The analysis of patients older than 60 years showed a significantly higher incidence of active CMV infection in the TT-ΔG/ΔG (83%) population with respect to CC-TT/TT (21%) and CT-TT/ΔG (40%) patients. Our data suggest a negative role of TT-ΔG/ΔG genotype in the CMV reactivation in Auto-SCT. The exposure to rituximab and the pre-infusion presence of anti CMV IgG also significantly influenced CMV reactivation.
Achieving successful hematopoietic stem cell transplantation (HSCT) relies on two fundamental pillars: effective mobilization and efficient collection through apheresis to attain the optimal graft ...dose. These cornerstones pave the way for enhanced patient outcomes. The primary challenges encountered by the clinical unit and collection facility within a transplant program encompass augmenting mobilization efficiency to optimize the harvest of target cell populations, implementing robust monitoring and predictive strategies for mobilization, streamlining the apheresis procedure to minimize collection duration while ensuring adequate yield, prioritizing patient comfort by reducing the overall collection time, guaranteeing the quality and purity of stem cell products to optimize graft function and transplant success, and facilitating seamless coordination between diverse entities involved in the HSCT process. In this review, we aim to address key questions and provide insights into the critical aspects of mobilizing and collecting hematopoietic stem cells for transplantation purposes.
Background: Positron emission tomography (PET) with the use of 18F-fluorodeoxyglucose (FDG), implemented with low-dosage computer tomography, is to be considered as the most important evolution of ...imaging in the management and assessment of classical Hodgkin lymphoma patients. Summary: According to Lugano response criteria, FDG-PET is mandatory to define metabolic response to frontline therapy and moreover it is important in the definition of nonresponders or refractory disease patients. Refractory disease is reported in about 15% of patients, with some variations based on the choice of first-line chemotherapy, and particularly in advanced stages, up to 40% eventually relapse within 3 years. Key Messages: The aim of this review was to highlight a practical way to use FDG-PET in the subset of HL, with some notes of its use in first-line patients, and particularly centered on relapsed or refractory setting with a final focus of the evaluation of response by FDG-PET in the new treatment era of immunocheckpoint inhibitors.
The multiple myeloma (MM) treatment has changed over the last years due to the introduction of novel drugs. Despite improvements in the MM outcome, MM remains an incurable disease. Daratumumab is a ...human IgGK monoclonal antibody targeting CD38 with tumor activity associated with immunomodulatory mechanism. In combination with standard of care regimens, including bortezomib (Vd) or lenalidomide (Rd), daratumumab prolonged progression‐free survival (PFS) in patients (pts) with relapsed/refractory multiple myeloma (RRMM) and in new diagnosis MM. We report the data of the MM GIMEMA Lazio group in 171 heavily treated pts who received daratumumab, lenalidomide and dexamethasone (DRd) or daratumumab, velcade and dexamethasone (DVd). The overall response rate was 80%, and the overall survival (OS) and PFS were 84% and 77%, respectively. In addition, pts treated with DRd showed a better median PFS compared to pts treated with DVd, at 12 and 24 months, respectively. The most common hematologic treatment‐emergent adverse events (TAEs) were neutropenia, thrombocytopenia, and anemia. The most common nonhematologic TAEs were peripheral sensory neuropathy and infections. Our data confirmed that DRd or DVd therapy is effective and safe in RRMM pts, and our real‐life analysis could support the physicians regarding the choice of optimal therapy in this setting of pts.
Introduction: The use of immune-checkpoints (anti PD-1/PD-L1) resulted very effective in the treatment of relapsed/refractory classical Hodgkin Lymphoma (cHL). T cell Ig and ITIM domains (TIGIT) is ...another immune checkpoint receptor known to negatively regulate T cell functions.
Methods: In this study, we investigated the expression of TIGIT in cHL microenvironment in order to find a potential new target for inhibitor therapy. TIGIT, PD-1 and PD-L1 expression was evaluated in 34 consecutive patients with cHL referred to Campus Bio-Medico University Hospital for diagnosis and treatment during the last eight years.
Results: TIGIT positivity was observed in 19/34 patients (56%), of these 11 (58%) had advanced stages and 10 (52%) B symptoms. Among the 8 patients with IPS ≥ 4, 6 (75%) were TIGIT +.
Out of the 19 TIGIT + (score 1 to 3) peritumoral T lymphocytes, 16 (84%) were also PD-1+. While out of 15 TIGIT- peritumoral T lymphocytes only 4 (27%) were PD-1+ and 11 (73%) were PD1- (P=0.001). Moreover all 15 TIGIT- patients were PD-L1+ (100%) while out of 19 TIGIT + patients, 11 (58%) were PD-L1+ and 8 (42%) PD-L1- (P=0.004).
Conclusion: This study indicate that the great majority of TIGIT+ patients are also PD-1+, while those who are TIGIT- are all PD-L1+. These results may offer a new therapeutic possibility in the treatment of Relapsed/Refractory (R/R) cHL by the use of anti-TIGIT monoclonal antibodies.
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High‐dose chemotherapy followed by autologous stem cell transplantation (auto‐SCT) is the standard treatment for young patient ≤65 years with multiple myeloma (MM). The role of auto‐SCT in elderly ...patients older than 70 years remains controversial in the era of novel agents and especially since the recent introduction of monoclonal antibodies (AbMo). In this study, we evaluated 12 patients with MM over 70 years old undergoing auto‐SCT (elderly graft cohort) in seven centers of GIMEMA Working Group Lazio. We compared the baseline characteristics, treatment and outcome with 97 MM elderly patients who did not receive auto‐SCT (nontransplant patients) from the same registry who were ≥ 70 years old, but did not undergo auto‐SCT. The median progression free survival (PFS) for graft versus no‐graft cohort was 56.4 versus 26.1 months, respectively. There was a trend for better PFS among graft compared to nontransplant patient (p = .1). On the other hand, the median overall survival for transplant versus nontransplant cohort was 107.6 versus 49.5 months (p = .02). Despite the small number of patients aged ≥70 years and ≤74 years, it seems that auto‐SCT is well tolerated, safe and effective. Therefore, we propose that it should be considered an important treatment option in the era of new drugs in elderly fit patients with MM.
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