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Background: Autologous anti‐CD19 chimeric antigen receptor (CAR) T‐cell therapy is an effective treatment for approximately 40% of relapsed/refractory large B cell lymphomas (LBCL), and early identification of patients at risk for relapse or progression after CAR T‐cell therapy represents a clinical need. Methods: The authors conducted a single‐center prospective study on 47 relapsed/refractory LBCL receiving CAR T‐cell therapy to evaluate the prognostic value of baseline and after infusion 18F‐fluorodeoxyglucose positron emission tomography (PET)‐computed tomography. Qualitative and quantitative metabolic parameters were evaluated before lymphodepletion, at day 30 and 90 post‐infusion. Results: Deep variation of standardized uptake value (SUV)mean between baseline and day 30 correlated with response at day 90 (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.01–2.2); p =.04) and better progression‐free survival (PFS) (HR, 0.63; 95% CI, 0.41–0.97); p =.04). In the overall population, 1‐year PFS was 63% for Deauville score (DS)1–3 and 39% for DS4–5 patients, respectively (p =.02), however, the prognostic role of DS was lost when survivals are analyzed by considering 38 patients not progressing at 30 days. In these patients, in partial response or stable disease, the combination of DS and variation of SUVmean allowed identification of three groups with different prognosis: patients with DS1–3 and those with DS4–5 and decreased SUVmean had similar 1‐year PFS of 62% and 61%, whereas patients with DS4–5 and increased SUVmean had a poorer 1‐year PFS of 33% (p =.04). Conclusions: PET parameters and association of DS and variation of SUVmean at 30 days could help in identify patients at high risk of CAR T‐cell failure. Lay summary: This is a single‐center prospective study on 47 lymphoma patients receiving commercial chimeric antigen receptor T‐cell therapy aimed to evaluate the prognostic value of baseline and after infusion 18F‐fluorodeoxyglucose positron emission tomography.Among patients in partial remission or stable disease at day 30, the authors observed two subgroups with significantly different prognosis; patients with Deauville score (DS)4–5 and a concomitant reduction of standardized uptake value (SUV)mean had higher probability of long‐lasting response than those with DS4–5 and an increase of SUVmean. The combination of qualitative and quantitative positron emission tomography parameters assessed at day 30 after chimeric antigen receptor T‐cell treatment could help identify prognostically different subgroups among patients with partial response or stable disease. At day 30, patients in partial remission (PR)/stable disease (SD) and a concomitant reduction of standardized uptake value (SUV)mean had higher probability of long‐lasting response than those with PR/SD and an increase of SUVmean. [ABSTRACT FROM AUTHOR]

Summary: Patients affected by lymphoid malignancies (LM) are frequently immune‐compromised, suffering increased mortality from COVID‐19. This prospective study evaluated serological and T‐cell responses after complete mRNA vaccination in 263 patients affected by chronic lymphocytic leukaemia, B‐ and T‐cell lymphomas and multiple myeloma. Results were compared with those of 167 healthy subjects matched for age and sex. Overall, patient seroconversion rate was 64·6%: serological response was lower in those receiving anti‐cancer treatments in the 12 months before vaccination: 55% vs 81·9% (P < 0·001). Anti‐CD20 antibody plus chemotherapy treatment was associated with the lowest seroconversion rate: 17·6% vs. 71·2% (P < 0·001). In the multivariate analysis conducted in the subgroup of patients on active treatment, independent predictors for seroconversion were: anti‐CD20 treatment (P < 0·001), aggressive B‐cell lymphoma diagnosis (P = 0·002), and immunoglobulin M levels <40 mg/dl (P = 0·030). The T‐cell response was evaluated in 99 patients and detected in 85 of them (86%). Of note, 74% of seronegative patients had a T‐cell response, but both cellular and humoral responses were absent in 13·1% of cases. Our findings raise some concerns about the protection that patients with LM, particularly those receiving anti‐CD20 antibodies, may gain from vaccination. These patients should strictly maintain all the protective measures. [ABSTRACT FROM AUTHOR]

Background: The authors describe a family with a high penetrance of plasma cell dyscrasias, suggesting inheritance of an autosomal dominant risk allele.Methods: The authors performed whole-exome sequencing and reported on a combined approach aimed at the identification of causative variants and risk loci, using the wealth of data provided by this approach.Results: The authors identified gene mutations and single-nucleotide polymorphisms of potential significance, and pinpointed a known risk locus for myeloma as a potential area of transmissible risk in the family.Conclusions: To the authors' knowledge, the current study is the first to provide a whole-exome sequencing approach to such cases, and a framework analysis that could be applied to further understanding of the inherited risk of developing plasma cell dyscrasias. Cancer 2017;123:3701-3708. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objectives The efficacy of a novel vaccine against influenza virus A ( H1 N1) in patients with hematologic malignancies is largely unknown. Methods We prospectively evaluated the humoral and cellular immune responses after one injection of monovalent adjuvanted 2009 H1 N1 vaccine in 47 adults with hematologic malignancies and 77 controls by hemagglutination-inhibition assay and flow-cytometry analysis on day 0, 28, 50, and 90. Results On day 28 postvaccination, patients had lower seroprotection (95.2% vs. 75.2%, P < 0.01) and seroconversion (88.7% vs. 51.1%, P < 0.01) rates, as well as geometric mean titer ( GMT; 256 vs. 134, P < 0.05), relative to controls. Response to vaccination varied according to the evaluated time point and the patient status: Patients not receiving chemotherapy had seroprotection and GMTs similar to controls in all time points, while patients receiving chemotherapy or allogeneic hematopoietic stem cell transplant ( HSCT) had lower seroprotection and seroconversion levels than controls on day 28 and 50. EMEA cutoffs for efficacy were reached from day 28 by patients in follow-up or under treatment and only from day 90 by those with HSCT, especially if still under immunosuppressants. Patients treated with immunomodulatory drugs had higher antibody responses in terms of seroprotection and GMTs. T- and NK cell-mediated responses mounted from day 50 and did not differ between patients and controls. Conclusions According to EMEA recommendation, H1 N1 vaccination strategy was effective at protecting most of the hematologic patients, but needed to be improved in those more immunocompromised. [ABSTRACT FROM AUTHOR]