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Central nervous system (CNS) relapse of mantle cell lymphoma (MCL) is a rare phenomenon with dismal prognosis, where no standard therapy exists. Since the covalent Bruton tyrosine kinase (BTK) inhibitor ibrutinib is effective in relapsed/refractory MCL and penetrates the blood–brain barrier (BBB), on behalf of Fondazione Italiana Linfomi and European Mantle Cell Lymphoma Network we performed a multicenter retrospective international study to investigate the outcomes of patients treated with ibrutinib or chemoimmunotherapy. In this observational study, we recruited patients with MCL with CNS involvement at relapse who received CNS-directed therapy between 2000 and 2019. The primary objective was to compare the overall survival (OS) of patients treated with ibrutinib or BBB crossing chemotherapy. A propensity score based on a multivariable binary regression model was applied to balance treatment cohorts. Eighty-eight patients were included. The median age at study entry was 65 years (range, 39-87), 76% were males, and the median time from lymphoma diagnosis to CNS relapse was 16 months (range, 1-122). Patients were treated with ibrutinib (n = 29, ibrutinib cohort), BBB crossing chemotherapy (ie, high-dose methotrexate ± cytarabine; n = 29, BBB cohort), or miscellaneous treatments (n = 30, other therapy cohort). Both median OS (16.8 vs 4.4 months; P = .007) and median progression-free survival (PFS) (13.1 vs 3.0 months; P = .009) were superior in the ibrutinib cohort compared with the BBB cohort. Multivariable Cox regression model revealed that ibrutinib therapeutic choice was the strongest independent favorable predictive factor for both OS (hazard ratio [HR], 6.8; 95% confidence interval [CI], 2.2-21.3; P < .001) and PFS (HR, 4.6; 95% CI, 1.7-12.5; P = .002), followed by CNS progression of disease (POD) >24 months from first MCL diagnosis (HR for death, 2.4; 95% CI, 1.1-5.3; P = .026; HR for death or progression, 2.3; 95% CI, 1.1-4.6; P = .023). The addition of intrathecal (IT) chemotherapy to systemic CNS-directed therapy was not associated with superior OS (P = .502) as the morphological variant (classical vs others, P = .118). Ibrutinib was associated with superior survival compared with BBB-penetrating chemotherapy in patients with CNS relapse of MCL and should be considered as a therapeutic option.

Objectives: High-dose CT (HDCT) is considered the gold-standard imaging for the measurements of skeletal muscle area (SMA), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and intramuscular adipose tissue (IMAT) areas in the abdomen. These parameters may reflect sarcopenia, which can have a prognostic impact in several oncological diseases. The aim of this study was to compare the agreement of measurements of SMA, VAT, SAT and IMAT areas between HDCT and low-dose CT (LDCT) of 18-fludeoxyglucose positron emission tomography (18F-FDG PET)/CT in elderly patients affected by Hodgkin lymphoma (HL). Methods: We retrospectively included 90 patients affected by HL who underwent baseline 18F-FDG-PET/CT and HDCT within a mean interval of 7 days. HDCT and LDCT images were analysed by two blinded observers using segmentation software (Slice-O-Matic, Tomovision) to quantify the areas. HDCT and LDCT measurements were compared using Bland–Altman plots and Passing-Bablock regression analyses. Pearson correlation coefficient (r) was used to correlate measurements from the two imaging modalities. Results: Comparison of HDCT and LDCT data demonstrated a strong correlation for measurement of VAT(r = 0.942, p < 0.0001), SAT (r = 0.894, p < 0.0001) and SMA (r = 0.934, p < 0.0001). Instead considering IMAT, correlation was good but less significant (r = 0.742). The mean difference between the two methods was found to be very small, with a difference of 1% for SAT,+6.1% for VAT,+2.5% for SMA and −1.9% for IMAT. Conclusion: LDCT of PET/CT is a safe, accurate and precise method for the measurements of skeletal muscle area, visceral and subcutaneous adipose tissue. Their measurements are reproducible and correlate closely with HDCT. Advances in knowledge: LLDCT of PET/CT is a safe and accurate method for the measurements of SMA, VAT and SAT; their measurements are closely correlated with HDCT. LDCT can be considered an accurate alternative tool for measuring abdominal fat and muscles in the clinical practice.

Background Elderly classical Hodgkin lymphoma (cHL) (ecHL) is a rare disease with dismal prognosis and no standard treatment. Fitness‐based approaches may help design appropriate treatments. Sarcopenia has been associated with an increased risk of treatment‐related toxicities and worse survival in various solid tumours, but its impact in ecHL is unknown. The aim of this retrospective multicentre study was to investigate the prognostic role of sarcopenia in ecHL. Methods We included newly diagnosed >64 years old cHL patients who performed a baseline comprehensive geriatric assessment and high‐dose computed tomography (CT) or 18fluorine‐fluorodeoxyglucose positron emission tomography/CT before any treatment. Sarcopenia was measured as skeletal muscle index (SMI, cm2/m2) by the analysis of high‐dose CT or low‐dose positron emission tomography/CT images at the L3 level. The specific cut‐offs for the SMI were determined by receiver operator curve analysis and compared with those proposed in literature and studied in diffuse large B‐cell lymphoma. Survival functions [progression‐free survival [PFS] and overall survival (OS)] were calculated for the whole population and for different subgroups defined as per different sarcopenia cut‐off levels. Results We included 154 patients (median age 71 years old, 76 female). The median L3‐SMI was 42 cm2/m2. The specific cut‐off derived in our male population was 45 cm2/m2; using this cut‐off, 27 male patients (35%) were defined as sarcopenic. After a median follow‐up of 5.9 years, the overall 5‐year PFS and OS rates were 53% and 65%, respectively, and were significantly shorter in sarcopenic male patients compared with non‐sarcopenic (PFS 31% vs. 61%, P = 0.008; OS 51% vs. 74%, P = 0.042). Applying diffuse large B‐cell lymphoma‐derived sarcopenic thresholds, there were no significant differences between sarcopenic and non‐sarcopenic patients for both PFS and OS, with a sole exception of a significant reduced PFS in sarcopenic male patients using Namakura cut‐off. The comprehensive geriatric assessment‐determined frail functional status was an independent adverse prognostic factor for both female and male patients. Conclusions Baseline evaluation of sarcopenia through radiological examinations performed for ecHL staging may help define a proportion of male patients with unfavourable outcome with current treatment strategies. Also the functional status evaluation could allow to identify a frail subgroup of patients with worse outcome.

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