RATIONALE:Very long-term survival has seldom been reported in primary central nervous system lymphoma (PCNSL) We report the updated outcome of patients treated in the C5R protocol from 1982 to 2001 in the Centre Leon Berard with a median follow-up of 35 years. METHODS:This retrospective analysis included the 43 patients treated within the C5R protocol combining HDMTX ARA-C and alkylating agents, with a consolidation with 20 Gys whole brain radiotherapy (WBRT) and a 30Gys boost. The first cohort includes the 25 patients of the initial C5R publication; the second cohort includes all subsequent 18 patients treated with C5R until 2001 in trials. Information on survival, relapse, second cancers, and post treatment leukoencephalopathy were collected. RESULTS:Thirty-nine deaths are documented. Median OS and PFS are 7.0 years (95%CI:1.9-12.1) and 4.7 years (95%CI: 0.33-9.01) respectively. Three patients are alive disease-free at 27, 28, and 44 years after treatment, 2 retired, 1 professionally active. While no prospective neurocognitive assessment was conducted, 14 patients presented neurocognitive deterioration for a projected incidence of 60% at 20 years. Second primary cancers were reported in 6 patients for a projected incidence of 28% at 20 years. The causes of death were PCNSL, neurotoxicity, and second cancers in 24 (55.8%), 5 (11.6%) and 5 (11.6%) of patients respectively, with 4 (9,3%) deaths during treatment and 1 (2.3%) of unknown cause. CONCLUSION:Very long-term survivors are observed in PCNSL treated 25-44 years ago. Late relapses, late neurocognitive decline and second cancers are common and important causes of deaths.

The management of large B-cell lymphomas (LBCL) has undergone major changes over the last 5 years. These changes reflect the availability of new therapies (immunotherapies, cell therapies, targeted molecules), but also a better compartmentalization of the entities and their specific clinical characteristics. Numerous first-, second- and third-line therapeutic strategies are available, and each practitioner is committed to selecting the treatment that offers the best balance between efficacy and toxicity. Advances in the understanding of LBCL biology, coupled with improvements in diagnostic and monitoring tools and therapeutic approaches, have significantly enhanced patient outcomes in recent years. In this article, we present a set of pragmatic guidelines developed by the LYSA (Lymphoma Study Association) for the management of LBCL. These guidelines address key aspects of diagnosis, staging, response evaluation, and treatment, integrating the latest evidence from clinical trials, expert consensus, and real-world practice. They aim to provide clinicians with a clear, practical framework to optimize care for patients with LBCL, ensuring that the best available evidence is translated into clinical practice.

Due to immunosuppressive treatment, COVID-19 vaccination is challenging in patients with B-cell lymphoma. We prospectively evaluated CD4, CD8 T-cell and serological responses to the COVID-19 mRNA vaccine in a cohort of patients treated for a B-cell lymphoma with anti-CD20 therapy. During lymphoma treatment, CD4, CD8, and CD19 cell dropped. While functional-specific CD4 and CD8 T-cell responses to SARS-CoV-2 were unaffected, vaccination in patients on treatment induced low specific antibody titers, contrasting with a preserved serological response when vaccination was completed before treatment initiation. Those findings reinforce a vaccinal strategy based on completion before lymphoma treatment, with a booster administered afterward.

Introduction: Diffuse large B-cell lymphoma (DLBCL) is one of the most common forms of blood cancer worldwide. Outcomes for patients with relapsed or refractory (r/r) DLBCL have remained dismal. Chimeric antigen receptor (CAR) T-cell therapy targeting the B-cell surface marker CD19 has recently emerged as a novel, effective approach capable of producing durable responses in r/r DLBCL patients. Indeed, nearly all r/r DLBCL patients in the United States are considered candidates for FDA-approved CAR-T therapy. However, CAR-T therapy has a number of major shortcomings. First, it has limited efficacy. The median progression-free survival (PFS) of r/r DLBCL patients treated with CAR-T therapy is roughly six months. Second, it has major toxicities. CAR-T therapy is associated with risk of life-threatening side effects such as cytokine release syndrome (CRS) and CAR-T cell-related encephalopathy syndrome (CRES). Third, it is highly expensive. Strategies for identifying, a priori, those patients likely to respond to this therapy could provide an important tool for clinical decision-making and improving outcomes in patients with r/r DLBCL. Methods & Results: We enrolled a real-world cohort of 161 r/r DLBCL patients treated with CD19-directed CAR-T therapy and applied whole exome and transcriptome sequencing on their pre-treatment biopsies to identify predictors of outcome. A number of clinical variables were associated with worse PFS or overall survival (OS) including a higher International Prognostic Index (IPI) score at diagnosis, involvement of multiple extranodal sites, poor performance status at the time of apheresis, high-grade CRES, and the need for ICU admission. Conversely, lower IPI score, activated B cell type (ABC) subtype of DLBCL, need for tocilizumab administration, and achievement of complete remission trended with more favorable survival outcomes. As expected, the most frequently mutated genes were involved in histone modification (e.g. KMT2D, CREBBP, EP300), B-cell signaling (e.g. MYD88, PIM1, CD79B) and DNA damage-response/repair (e.g. TP53, DDX3X, BCL6, ATM). Gene mutations associated with the least favorable prognosis were SOCS1, BCL7A, and MYC, while HIST1H1E, CD79B, and MPEG1 mutations were associated with a favorable prognosis. We further developed a supervised approach for analysis and validation of gene expression profiles and their association with outcome. We first divided the patients into independent training and test sets. In the training set, we applied the Cox proportional hazards model to identify individual genes that were associated with PFS in CAR-T therapy treated patients. We identified two gene expression signatures that were associated with superior outcomes and poor outcomes, respectively. These two signatures were combined to generate a single prognostic score that comprised the genomic model that was validated in the independent test set. The first “low-risk” signature appeared to be derived predominantly from tumor cells with a number of B-cell related genes including CD19, PAX5, CD79A and CXCR5 as well as genes associated with the NF-kB pathway. The second signature included macrophage-related genes such as CD163, FCGR1A (CD64) and MSR1, as well as genes associated with MYC targets, ferroptosis and iron transport. We found that the model distinguished patients with significantly different outcomes. Patients in the lowest quartile of prognostic scores had a median PFS of 2.8 months, while those in the highest quartile of scores had a significantly longer median PFS of 18 months (Wilcoxon rank-sum test p< 0.001). 73% of patients identified as having favorable risk achieved complete remission. Conclusion: The management of CAR-T treated patients remains challenging owing to limitations in efficacy, cost and side effects. Our study indicates that genomic features of the tumor prior to treatment are significantly associated with response to CAR-T therapy in DLBCL. We anticipate that the translation of these findings into clinical practice will enable the development of precision medicine approaches using CAR-T therapy in in this challenging disease.

SummaryIdecabtagene vicleucel (ide‐cel), a chimeric antigen receptor T‐cell therapy targeting B‐cell maturation antigen (BCMA), received early access program (EAP) authorization in France in April 2021 for relapsed/refractory multiple myeloma (RRMM). We conducted a real‐world registry‐based multicentre observational study in 11 French hospitals to evaluate ide‐cel outcomes. Data from 176 RRMM patients who underwent apheresis between June 2021 and November 2022 were collected from the French national DESCAR‐T registry. Of these, 159 patients (90%) received ide‐cel. Cytokine release syndrome occurred in 90% with 2% grade ≥3, and neurotoxicity occurred in 12% with 3% grade ≥3. Over the first 6 months, the best overall response and ≥complete response rates were 88% and 47% respectively. The median progression‐free survival (PFS) from the ide‐cel infusion was 12.5 months, the median overall survival (OS) was 20.8 months and the estimated OS rate at 12 months was 73.3%. Patients with extra‐medullary disease (EMD) had impaired PFS (6.2 months vs. 14.8 months). On multivariable analysis, EMD and previous exposure to BCMA‐targeted immunoconjugate or T‐cell‐redirecting GPRC5D bispecific antibody were associated with inferior PFS. Our study supports ide‐cel's feasibility, safety and efficacy in real‐life settings, emphasizing the importance of screening for EMD and considering prior treatments to optimize patient selection.

Metabolic programs contribute to hematopoietic stem and progenitor cell (HSPC) fate, but it is not known whether the metabolic regulation of protein synthesis controls HSPC differentiation. Here, we show that SLC7A1/CAT1-dependent arginine uptake and its catabolism to the polyamine spermidine control human erythroid specification of HSPCs via activation of the eukaryotic translation initiation factor 5A (eIF5A). eIF5A activity is dependent on its hypusination, a post-translational modification resulting from the conjugation of the aminobutyl moiety of spermidine to lysine. Notably, attenuation of hypusine synthesis in erythroid progenitors--by inhibition of deoxyhypusine synthase--abrogates erythropoiesis but not myeloid cell differentiation. Proteomic profiling reveals mitochondrial translation to be a critical target of hypusinated eIF5A and accordingly, progenitors with decreased hypusine activity exhibit diminished oxidative phosphorylation. This impacted pathway is critical for eIF5A-regulated erythropoiesis as interventions augmenting mitochondrial function partially rescue human erythropoiesis under conditions of attenuated hypusination. Levels of mitochondrial ribosomal proteins were especially sensitive to the loss of hypusine and we find that the ineffective erythropoiesis linked to haploinsufficiency of RPS14 in del(5q) myelodysplastic syndrome is associated with a diminished pool of hypusinated eIF5A. Moreover, patients with RPL11-haploinsufficient Diamond-Blackfan anemia as well as CD34+ progenitors with downregulated RPL11 exhibit a markedly decreased hypusination in erythroid progenitors, concomitant with a loss of mitochondrial metabolism. Thus, eIF5A-dependent protein synthesis regulates human erythropoiesis and our data reveal a novel role for RPs in controlling eIF5A hypusination in HSPC, synchronizing mitochondrial metabolism with erythroid differentiation.

Exhaustion describes a condition in which T cells are unable to perform any function. It has been characterized by chronic infections and cancers.1 Various features within the tumour microenvironment led to dysfunction of T infiltrating lymphocytes, such as antigen persistence, nutrient deprivation and/or PDCD1 demethylation.2 This gene codes for the protein PD-1, whose expression is the most known feature of exhaustion. Targeting PD-1 with nivolumab or pembrolizumab led to impressive clinical success in the context of various metastatic tumours and Hodgkin lymphoma.3 Even though single-agent anti-PD1 showed low and transient antitumor activity in R/R DLBCL,4 with the exception of patients with HIV-related lymphoma, that may benefit of a long-term disease control.5 About 60 per cent of patients treated with axicabtagene ciloleucel for a relapsing or refractory diffuse large B cell lymphoma (R/R DLBCL) do not achieve a persistent response.6 Massive research effort has been undertaken to dissect CAR T cell failure. Among other causes, absence/low expansion, functionality or persistence of those engineered T cells had been related to exhaustion features. These characteristics have been described among harvested T cells, CAR T cells from the final product and/or circulating CAR T cells, themselves linked to tumour burden, tumour microenvironment and/or systemic inflammation.7 In this issue, Gazeau et al. report on their experience with nivolumab in that context. With that drug, they have been trying to rescue 11 patients that did not achieve a complete remission 30 days after axicabtagene ciloleucel for a R/R DLBCL. They treated patients in 3 different situations. The "primary refractory" group included patients who showed stable or progressive disease at initial evaluation, the "booster" group included patients who achieved a partial response and were belief to require additional therapy, and the "salvage" group included patients who progressed after achieving a partial response and therefore required salvage therapy. Nivolumab was administrated every 2 weeks, and efficacy was evaluated by PET/CT after four injections. Regarding safety, four mild respiratory tract infections were reported, and no CRS/ICANS was observed. Four patients achieved a complete response after 2 months of treatment, two patients were in the situation of partial response at D30 and two others were experiencing relapsing disease after a partial response. A second expansion of circulating CAR T cells was observed, after a single injection of nivolumab, which argues on reversion of CAR T cell exhaustion: Cmax was 0.035 G/L, lower that the initial expansion but following a long period when the CAR T cells were undetectable. Moreover, the secretion of pro-inflammatory cytokines is probably reflecting the functionality of those CAR T cells. Another group recently reported three patients with early progression or relapse, after being treated with 4-1BB costimulated CD19 CAR T cells, who responded to pembrolizumab.8 Ten out of the 12 patients treated in this study experienced a second expansion of circulating CAR T cell. Interestingly, pretreatment biopsy from seven out of nine patients had positive PD1 ligand expression (PD-L1). Other groups described that PD-L1 expression by DLBCL tumour cells is associated with activated B cell genotype, as well as poor outcomes.9 Taken together, those clinical data suggest a potential therapeutic benefit of the reversion of CAR T cell exhaustion with anti-PD-1 therapy. Ongoing clinical trials will help to determine the best candidates and modalities for such salvage.

INTRODUCTION - Relapsed-refractory B-cell non-Hodgkin's lymphomas (R/R-B-NHL) treatment remains challenging. In this context, CAR T-cell therapy has shown sustained efficacy in 40-60% of patients. Early progressions and pseudo-progression have been described after CAR T-cell therapy, but data are scarce. This study aims to assess incidence, risk factors and outcomes of early progression in patients treated with CAR T-cells for R/R B-NHL. PATIENTS & METHODS - All patients were consecutively treated at the University Hospital of Montpellier with a commercial CAR T-cells for R/R-B-NHL between December 2019 and June 2022 and included in the CARTBANK cohort (ID RCB: 2019-A03032-55, NCT04290000). Cases were retrospectively reviewed for early progression. No antitumor treatment was initiated before the day 28 evaluation. Early Progressions of Undetermined Significance (EPUS) were defined as either: self-reported symptom of lymphoma (possible EPUS), clinically assessed progression (probable), or measured through imaging procedure (highly probable) after CAR T-cell infusion and before day 28 (D28) post evaluation. Pseudo-progression was defined as EPUS with partial or complete response on D28 evaluation. On the contrary, hyper-progression was defined as EPUS with confirmed progression on D28 evaluation. RESULTS - A total of 105 patients were included in the study, with a median age of 65 years (interquartile range: 55;70]) and 70% were male. Diffuse large B-cell lymphoma (DLBCL) was the most common histology (89%), followed by follicular lymphoma (6%) and mantle cell lymphoma (5%). Patients had received a median of 2 previous lines of anti-cancer therapy [2;3]. Axicabtagene-ciloleucel was used in 77% of the cases, tisagenlecleucel in 18%, and brexucabtagene-autoleucel in 5%. Overall 18 patients (17%) had EPUS: 2 possible EPUS (11%), 6 (33%) probable EPUS and 10 (56%) highly probable EPUS (panel A). D28 evaluation revealed that most of EPUS were pseudo-progressions (n=13/18, 72%). Hyper-progression was observed in one patient (6%) and 4 patients (22%) died before first metabolic assessment and remained unclassified (panel B). The cause of death was suspected of progression for three of them and sepsis for one. All EPUS occurred before day 21 (median: 7 days [3;8]). Comparison of patients with and without EPUS showed that no clear risk factors for EPUS were identified. EPUS occurrence had no impact on PFS nor OS. The blood expansion of CAR-T cells and their level of exhaustion were monitored by multi-parametric flow cytometry. Regarding these pharmacokinetic parameters, no significant difference was obtained between patients with and without EPUS. Analysis of data regarding total metabolic volume is ongoing and will be presented. DISCUSSION - In this cohort, EPUS is observed in 17% of patients after CAR T-cells infusion for R/R B-NHL. Most of EPUS are related to pseudo-progression. These results should be confirmed in a dedicated study. Thus, early treatment before first evaluation should be avoided.

Patients with previous CD19 directed chimeric antigen receptor T cell therapy (CAR T)-cell therapy have a prolonged vulnerability to viral infections. Coronavirus diseases 2019 (COVID-19) has a great impact and has previously been shown to cause high mortality in this population. Until now, real world data of the impact of vaccination and treatment on patients with COVID-19 after CD19 directed CAR T-cell therapy are lacking. Therefore, this multicenter retrospective study was conducted with data from the EPICOVIDEHA survey. Sixty-four patients were identified. The overall mortality caused by COVID-19 was 31%. Patients infected with the Omicron variant had a significantly lower risk of death due to COVID-19 compared to patients infected with previous variants (7% versus 58% (P=0.012)). Twenty-six patients were vaccinated at time of COVID-19 diagnosis. Two vaccinations showed marked but unsignificant reduction risk of COVID-19 caused mortality (33.3% versus 14.2% (P=0.379)).Also the course of disease appears milder with less frequent ICU admissions (39% versus 14% (P=0.054)) and shorter duration of hospitalization (7 versus 27.5 days (P=0.022)). Of the available treatment options, only monoclonal antibodies seemed to be effectively reducing mortality from 32% to zero (P=0.036). We conclude that survival rates of CAR T-cell recipients with COVID-19 improved over time and that the combination of prior vaccination and monoclonal antibody treatment significantly reduces their risk of death.

Background and Objectives Chimeric antigen receptor (CAR) T-cell therapies have dramatically improved the prognosis of patients with relapsed or refractory hematologic malignancies; however, cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome (ICANS) occur in ∼100 and 50% of patients, respectively. This study aimed to determine whether EEG patterns may be considered as diagnostic tools for ICANS. Methods Patients who received CAR T-cell therapy at Montpellier University Hospital between September 2020 and July 2021 were prospectively enrolled. Neurologic signs/symptoms and laboratory parameters were monitored daily for 14 days after CAR T-cell infusion. EEG and brain MRI were performed between day 6 and 8 after CAR T-cell infusion. EEG was performed again on the day of ICANS occurrence, if outside this time window. All collected data were compared between patients with and without ICANS. Results Thirty-eight consecutive patients were enrolled (14 women; median age: 65 years, interquartile range: [55–74]). ICANS was observed in 17 of 38 patients (44%) after a median time of 6 days after CAR T-cell infusion (4–8). The median ICANS grade was 2 (1–3). Higher C-reactive protein peak (146 mg/L [86–256], p = 0.004) at day 4 (3–6), lower natremia (131 mmol/L [129–132], p = 0.005) at day 5 (3–6), and frontal intermittent rhythmic delta activity (FIRDA, p < 0.001) on EEG between days 6 and 8 after infusion were correlated with ICANS occurrence. FIRDA was only observed in patients with ICANS (N = 15/17, sensitivity of 88%) and disappeared after ICANS resolution, usually after steroid therapy. Except for hyponatremia, no other toxic/metabolic marker was associated with FIRDA (p = 0.002). The plasma concentration of copeptin, a surrogate marker of antidiuretic hormone secretion, assessed at day 7 after infusion, was significantly higher in patients with (N = 8) than without (N = 6) ICANS (p = 0.043). Discussion FIRDA is a reliable diagnostic tool for ICANS, with a sensitivity of 88% and a negative predictive value of 100%. Moreover, as this EEG pattern disappeared concomitantly with ICANS resolution, FIRDA could be used to monitor neurotoxicity. Finally, our study suggests a pathogenic pathway that starts with increased C-reactive protein, followed by hyponatremia and eventually ICANS and FIRDA. More studies are required to confirm our results. Classification of Evidence This study provides Class III evidence that FIRDA on spot EEG accurately distinguishes patients with ICANS compared with those without after CAR T-cell therapy for hematologic malignancy.

Data on outcome of patients with mantle cell lymphoma (MCL) and COVID-19 infection are limited. The European MCL (EMCL) registry is a centralized registry of the EMCL network, collecting real-world information about treatments and disease courses. During the COVID-19 pandemic, additional data on MCL patients with COVID-19 infection were collected, aiming to identify risk factors for mortality from COVID-19. In our retrospective, multicenter, international study, we collected data from 63 MCL patients with a median age of 64 years (range, 44-84) in 9 countries with evidence of a COVID-19 infection between February 2020 and October 2021. The overall mortality rate was high (44.4%), especially in hospitalized patients (61%) and in patients with need for intensive care unit care (94%). Patients receiving rituximab had significantly poorer survival than patients not receiving rituximab (P = 0.04). Our data highlight the importance of prevention strategies and underline the need for effective vaccination in this vulnerable cohort.

de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

The following clinical and epidemiological data from patients with a laboratory-based diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are collected: underlying conditions before SARS-CoV-2, hematological malignancy status, and management before SARS-CoV-2 infection. The severity of COVID-19 is graded according to the China Centers for Disease Control and Prevention and the cause of mortality. 13

Limited data are available on breakthrough COVID-19 in patients with hematologic malignancy (HM) after anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Adult patients with HM, ≥1 dose of anti-SARS-CoV-2 vaccine, and breakthrough COVID-19 between January 2021 and March 2022 were analyzed. A total of 1548 cases were included, mainly lymphoid malignancies (1181 cases, 76%). After viral sequencing in 753 cases (49%), the Omicron variant was prevalent (517, 68.7%). Most of the patients received ≤2 vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received COVID-19-specific treatment. After 30-day follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with the Omicron variant was 7.9%, comparable to other variants, with a significantly lower 30-day mortality rate than in the prevaccine era (31%). In the univariable analysis, older age (P < .001), active HM (P < .001), and severe and critical COVID-19 (P = .007 and P < .001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (P < .001). In the multivariable model, older age, active disease, critical COVID-19, and 2-3 comorbidities were correlated with a higher mortality, whereas monoclonal antibody administration, alone (P < .001) or combined with antivirals (P = .009), was protective. Although mortality is significantly lower than in the prevaccination era, breakthrough COVID-19 in HM is still associated with considerable mortality. Death rate was lower in patients who received monoclonal antibodies, alone or in combination with antivirals.

Patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we describe and analyze the outcome of 366 adult patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between February 2020 and January 2022. Median follow-up was 70.5 days (IQR 0-609). Most used targeted drugs were Bruton-kinase inhibitors (BKIs) (N= 201, 55%), anti-CD20 other than rituximab (N=61, 16%), BCL2 inhibitors (N=33, 9%) and lenalidomide (N=28, 8%).Only 16.2% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Mortality was 24% (89/366) on day 30 and 36%(134/366) on the last day of follow-up. Age >75 years (p<0.001, HR 1.036), active malignancy (p<0.001, HR 2.215), severe COVID-19 (p=0.017, HR 2.270) and admission to ICU (p<0.001, HR 5.751) were risk factors for mortality at last day of follow up. There was no difference in OS rates in NHL vs CLL patients (p=0.306), nor in patients treated with or without BKIs (p=0.151). Mortality in ICU was 66% (CLL 61%, NHL 76%). Overall mortality rate decreased according to vaccination status, being 39% in unvaccinated patients, 32% and 26% in those having received one or two doses, respectively, and 20% in patients with a booster dose (p=0.245). Overall mortality rate dropped from 41% during the first semester of 2020 to 25% at the last semester of 2021. These results show increased severity and mortality from COVID-19 in LPDs patients treated with targeted drugs.

In a Plenary Paper, Mittelman and colleagues assess the relative clinical efficacy of mRNA vaccination on COVID-19 disease incidence and outcomes in patients with hematologic malignancies compared with healthy matched controls. This population-based study from Israel links prior observations of poor serologic responses to vaccination to higher risk for breakthrough infection, hospitalization, and death in patients with blood cancer, especially those on active antineoplastic therapy. In an accompanying Letter to Blood, Pagano et al provide supportive data using a multination survey approach to capture outcomes for COVID-19 in vaccinated patients with hematologic neoplasms. They also emphasize the higher risk among patients with lymphoid malignancies. Together, these findings argue for both continued deployment of booster programs and ongoing public health guidance for this vulnerable group.

Patients with hematological malignancy and COVID-19 display a high mortality rate. In such patients, immunosuppression due to underlying disease and previous specific treatments impair humoral response, limiting viral clearance. Thus, COVID-19 convalescent plasma (CCP) therapy appears as a promising approach through the transfer of neutralizing antibodies specific to SARS-CoV-2. We report the effect of CCP in a cohort of 112 patients with hematological malignancy and COVID-19 and a propensity score analysis on subgroups of patients with B-cell lymphoid disease treated ( n = 81) or not ( n = 120) with CCP between May 1, 2020 and April 1, 2021. The overall survival of the whole cohort was 65% (95% CI = 56–74.9) and 77.5% (95% CI = 68.5–87.7) for patients with B-cell neoplasm. Prior anti-CD20 monoclonal antibody therapy was associated with better overall survival, whereas age, high blood pressure, and COVID-19 severity were associated with a poor outcome. After an inverse probability of treatment weighting approach, we observed in anti-CD20–exposed patients with B-cell lymphoid disease a decreased mortality of 63% (95% CI = 31–80) in the CCP-treated group compared to the CCP-untreated subgroup, confirmed in the other sensitivity analyses. Convalescent plasma may be beneficial in COVID-19 patients with B-cell neoplasm who are unable to mount a humoral immune response.