Hereditary combined vitamin K-dependent clotting factors deficiency (VKCFD) is a rare congenital bleeding disorder resulting from variably decreased levels of coagulation factors II, VII, IX and X as well as natural anticoagulants protein C, protein S and protein Z. The spectrum of bleeding symptoms ranges from mild to severe with onset in the neonatal period in severe cases. The bleeding symptoms are often life-threatening, occur both spontaneously and in a surgical setting, and usually involve the skin and mucosae. A range of non-haemostatic symptoms are often present, including developmental and skeletal anomalies. VKCFD is an autosomal recessive disorder caused by mutations in the genes of either gamma-glutamyl carboxylase or vitamin K2,3-epoxide reductase complex. These two proteins are necessary for gamma-carboxylation, a post-synthetic modification that allows coagulation proteins to display their proper function. The developmental and skeletal anomalies seen in VKCFD are the result of defective gamma-carboxylation of a number of non-haemostatic proteins. Diagnostic differentiation from other conditions, both congenital and acquired, is mandatory and genotype analysis is needed to confirm the defect. Vitamin K administration is the mainstay of therapy in VKCFD, with plasma supplementation during surgery or severe bleeding episodes. In addition, prothrombin complex concentrates and combination therapy with recombinant activated FVII and vitamin K supplementation may constitute alternative treatment options. The overall prognosis is good and with the availability of several effective therapeutic options, VKCFD has only a small impact on the quality of life of affected patients.

Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) exhibits substantial clinical heterogeneity and poor prognosis in relapsed/refractory (R/R) settings. PRO-MIND is a prospective, multicenter real-world study evaluating tafasitamab–lenalidomide followed by tafasitamab monotherapy in patients with transplant-ineligible R/R DLBCL in Italy. This ad hoc, cross-sectional, baseline analysis aimed to characterize health-related quality of life (HRQoL) and symptom burden before tafasitamab–lenalidomide initiation in the PRO-MIND cohort. Methods: Thirty-eight patients across 30 centers completed the EORTC QLQ-C30 and QLQ-NHL-HG29 questionnaires at pretreatment baseline, prior to starting tafasitamab–lenalidomide. EORTC QLQ-C30 scores (0–100) were compared with age-specific normative values for the Italian general population using Welch’s t-test. Differences of ≥5 points were considered clinically meaningful and ≥10 points clearly clinically important. Effect sizes (Cohen’s d) were calculated to complement p-values for between-group comparisons. Results: Compared with normative data, the PRO-MIND cohort had significantly lower EORTC QLQ-C30 functioning scores for physical (Δ 12.7, p = 0.0135), role (Δ 16.1, p = 0.0168), social (Δ 15.2, p = 0.0019), and cognitive (Δ 8.5, p = 0.0460) functioning. Symptom scales revealed worse fatigue (Δ 14.8, p = 0.0097), insomnia (Δ 13.9, p = 0.0291), appetite loss (Δ 9.4, p = 0.0435), and pain (Δ 8.7, p = 0.0430) in the PRO-MIND cohort versus normative data, with effect sizes in the small-to-moderate range. EORTC QLQ-NHL-HG29 scores indicated a high prevalence of concerns about future health (84.2%), disease recurrence (81.6%), and dependency (78.9%), as well as physical symptoms, including lack of energy (71.1%), sleep difficulties (63.2%), and pain or discomfort (60.5%). Conclusions: This cross-sectional, baseline-only analysis of the PRO-MIND real-world cohort showed that patients with transplant-ineligible R/R DLBCL scheduled to receive tafasitamab–lenalidomide already had pronounced impairments in physical, role, social, and cognitive functioning, along with substantial fatigue, insomnia, pain, appetite loss, and psychological concerns. These baseline benchmarks underscore the importance of systematic HRQoL assessment and targeted supportive interventions focusing on these domains before and during treatment. Future longitudinal PRO-MIND analyses will complement these findings by describing how HRQoL evolves after tafasitamab–lenalidomide initiation.