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Objectives To compare brain MRI findings in progressive multifocal leukoencephalopathy (PML) associated to rituximab and natalizumab treatments and HIV infection. Materials and methods In this retrospective, multicentric study, we analyzed brain MRI exams from 72 patients diagnosed with definite PML: 32 after natalizumab treatment, 20 after rituximab treatment, and 20 HIV patients. We compared T2- or FLAIR-weighted images, diffusion-weighted images, T2*-weighted images, and contrast enhancement features, as well as lesion distribution, especially gray matter involvement. Results The three PML entities affect U-fibers associated with low signal intensities on T2*-weighted sequences. Natalizumab-associated PML showed a punctuate microcystic appearance in or in the vicinity of the main PML lesions, a potential involvement of the cortex, and contrast enhancement. HIV and rituximab-associated PML showed only mild contrast enhancement, punctuate appearance, and cortical involvement. The CD4/CD8 ratio showed a trend to be higher in the natalizumab group, possibly mirroring a more efficient immune response. Conclusion Imaging features of rituximab-associated PML are different from those of natalizumab-associated PML and are closer to those observed in HIV-associated PML. Key Points • Nowadays, PML is emerging as a complication of new effective therapies based on monoclonal antibodies. • Natalizumab-associated PML shows more inflammatory signs, a perivascular distribution “the milky way,” and more cortex involvement than rituximab- and HIV-associated PML. • MRI differences are probably related to higher levels of immunosuppression in HIV patients and those under rituximab therapy.

Primary mediastinal B‐cell lymphoma (PMBL) is often cured with dose‐dense anthracycline‐based regimens but the prognosis at relapse or progression remains poor. While anti‐CD19 CAR‐T cell therapy has dramatically improved outcomes in relapsed or refractory large B‐cell lymphoma, far less is known about their efficacy in PMBL. Using the systematic record of all patients treated with CAR‐T cells prospectively included in the DESCAR‐T registry in France, along with centrally reviewed positon‐emission tomography (PET) imaging, we describe the outcomes and key determinants of treatment success in PMBL patients treated over a 6‐year period. Among 82 patients infused in the registry we observed a best complete response (CR) rate, 2‐year progression‐free survival (PFS), and 2‐year overall survival (OS) of 68.1%, 57.4%, and 73.8%, respectively. Outcomes were even better for the 62 patients infused with axicabtagene ciloleucel, with best CR rate, 2‐year PFS, and 2‐year OS reaching 74.5%, 70.4%, and 86.9%, respectively. Achieving a Deauville score of 1–4 or a ΔSUVmax reduction of more than 24% at the 1‐month evaluation was associated with excellent outcomes, whereas increased total metabolic tumor volume baseline PET increased the risk of treatment failure. Surprisingly, neither the response to bridging therapy nor the type of bridging therapy (chemotherapy versus immune checkpoint inhibitors) were associated with long‐term outcomes. In conclusion, this study confirms that anti‐CD19 CAR‐T cells as a valid standard‐of‐care for relapsed and refractory PMBL and highlights key determinants of treatment success.

Relapse is a major event in patients with lymphoma. Therefore, early detection may have an impact on quality of life and overall survival. Patient-reported outcome measures have demonstrated clinical benefits for patients with lung cancer; however, evidence is lacking in patients with lymphoma. We evaluated the effect of a web-mediated follow-up application for patients with lymphoma at high risk of relapse. This study aims to demonstrate that monitoring patients via a web application enables the detection of at least 30% more significant events occurring between 2 systematic follow-up consultations with the specialist using an electronic questionnaire. We conducted a prospective, randomized phase 3 trial comparing the impact of web-based follow-up (experimental arm) with a standard follow-up (control arm). The trial was based on a 2-step triangular test and was designed to have a power of 90% to detect a 30% improvement in the detection of significant events. A significant event was defined as a relapse, progression, or a serious adverse event. The study covered the follow-up period after completion of first-line treatment or relapse (24 months). Eligible patients were aged 18 years and older and had lymphoma at a high risk of relapse. In the experimental arm, patients received a 16-symptom questionnaire by email every 2 weeks. An email alert was sent to the medical team based on a predefined algorithm. The primary objective was assessed after the inclusion of the 40th patient. The study was continued for the duration of the analysis. A total of 52 patients were included between July 12, 2017, and April 7, 2020, at 11 centers in France, with 27 in the experimental arm and 25 in the control arm. The median follow-up was 21.3 (range 1.3-25.6) months, and 121 events were reported during the study period. Most events occurred in the experimental arm (83/119, 69.7%) compared with 30.2% (36/119) in the control arm. A median number of 3.5 (range 1-8) events per patient occurred in the experimental arm, and 1.8 (range 1-6) occurred in the control arm (P=.01). Progression and infection were the most frequently reported events. Further, 19 patients relapsed during follow-up: 6 in the experimental arm and 13 in the control arm (P<.001), with a median follow-up of 7.7 (range 2.8-20.6) months and 6.7 (range 1.9-16.4) months (P=.94), respectively. Statistical analysis was conducted after including the 40th patient, which showed no superiority of the experimental arm over the control arm. The study was therefore stopped after the 52nd patient was enrolled. The primary objective was not reached; however, patient-reported outcome measures remain essential for detecting adverse events in patients with cancer, and the electronic monitoring method needs to demonstrate its effectiveness and comply with international safety guidelines.

Introduction We retrospectively analysed bortezomib–dexamethasone–rituximab (BDR) combination in patients with Waldenström macroglobulinaemia (WM) in a real world setting. Methods A total of 87 patients were included: 49 patients (56%) were treated in frontline, 22 (25%) in second line and 16 (19%) in third or further line settings. A log‐rank test was used to compare overall and event‐free survival (OS and EFS) whereas a Gray's test was performed to compare cumulative incidence of deaths and relapse (CID and CIR) according to the IPSS‐WM groups, MYD88/CXCR4 mutational status and line of therapy. Results The overall response rate was 88% with five patients (6%) achieving complete response, 20 (24%) very good partial response, 38 (45%) partial response and 11 (13%) minor response. The median time to achieve the best overall response was 9 months and the median EFS was 33 months for whole cohort. Patients treated in third line or further relapse settings had significantly lower median EFS compared to those treated in second‐ or first‐line setting (13 vs. 36 vs. 47 months, respectively, p = 0.01) and a higher 7‐year CID (50% vs. 13% vs. 12% respectively, p = 0.02). Among patients for whom mutational status was available, MYD88L265P mutation or double mutation MYD88/CXCR4 did not influence OS or EFS. Severe peripheral neurotoxicity affected 7% of patients and 52 (62%) patients relapsed or died as result of WM whereas 21 patients (24%) died of unrelated causes. Conclusion BDR represents an interesting chemo‐free, fixed duration regimen for patients in first or second line, regardless of mutational status. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission.

Background Besides International Prognostic Index (IPI) score, baseline prognostic factors of post-transplant lymphoproliferative disorders (PTLD) are poorly identified due to the rarity of the disease. New indexes derived from healthy organ uptake in baseline 18F-FDG PET/CT have been studied in immunocompetent lymphoma patients. The aim of this study is to evaluate the performances of the cerebellum-to-liver uptake ratio (denoted as CLIP) as a prognostic factor for PFS and OS. This retrospective multicenter study is based on patients with PTLD included in the K-VIROGREF cohort. The previously published threshold of 3.24 was used for CLIP in these analyses. Results A total of 97 patients was included with a majority of monomorphic diffuse large B-cell lymphoma subtype (78.3%). Both IPI score (≥ 3) and CLIP (< 3.24) were significant risk factors of PFS with corresponding hazard ratios of 2.0 (1.0–4.0) and 2.4 (1.3–4.5) respectively. For OS, CLIP was not significant and resulted in a hazard ratio of 2.6 ( p  = 0.059). Neither IPI score or Total Metabolic Tumor Volume reached significance for OS. Conclusion CLIP is a promising predictor of PFS and perhaps OS in PTLD. Further prospective studies are needed to confirm these results.

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) have both demonstrated impressive clinical activity in relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). In this study, we analyzed the outcome of 809 patients with R/R DLBCL after two or more previous lines of treatment who had a commercial chimeric antigen receptor (CAR) T cells order for axi-cel or tisa-cel and were registered in the retrospective French DESCAR-T registry study ( NCT04328298 ). After 1:1 propensity score matching ( n  = 418), the best overall response rate/complete response rate (ORR/CRR) was 80%/60% versus 66%/42% for patients treated with axi-cel compared to tisa-cel, respectively ( P  < 0.001 for both ORR and CRR comparisons). After a median follow-up of 11.7 months, the 1-year progression-free survival was 46.6% for axi-cel and 33.2% for tisa-cel (hazard ratio (HR) = 0.61; 95% confidence interval (CI), 0.46–0.79; P  = 0.0003). Overall survival (OS) was also significantly improved after axi-cel infusion compared to after tisa-cel infusion (1-year OS 63.5% versus 48.8%; HR = 0.63; 95% CI, 0.45–0.88; P  = 0.0072). Similar findings were observed using the inverse probability of treatment weighting statistical approach. Grade 1–2 cytokine release syndrome was significantly more frequent with axi-cel than with tisa-cel, but no significant difference was observed for grade ≥3. Regarding immune effector cell-associated neurotoxicity syndrome (ICANS), both grade 1–2 and grade ≥3 ICANS were significantly more frequent with axi-cel than with tisa-cel. In conclusion, our matched comparison study supports a higher efficacy and also a higher toxicity of axi-cel compared to tisa-cel in the third or more treatment line for R/R DLBCL. Analysis of outcomes of over 800 patients with relapsed/refractory diffuse large B cell lymphoma, treated with commercially available CAR T cell therapy, supports higher efficacy and also a higher toxicity of axicabtagene ciloleucel compared to tisagenlecleucel as the third or more treatment line for this type of tumor.

Background Extranodal nasal-type NK/T-cell lymphoma is a rare and severe disease. Considering the rarity of this lymphoma in Europe, we conducted a multicentric retrospective study on nasal-type NK/T cell lymphoma to determine the optimal induction strategy and identify prognostic factors. Methods Thirty-six adult patients with nasal-type NK/T-cell lymphoma were recruited and assessed. In total, 80 % of patients were classified as having upper aerodigestive tract NK/T-cell lymphoma (UNKTL) and 20 % extra-upper aerodigestive tract NK/T-cell lymphoma (EUNKTL). Results For advanced-stage disease, chemotherapy alone (CT) was the primary treatment (84 % vs. 10 % for combined CT + radiation therapy (RT), respectively), while for early-stage disease, 50 % of patients received the combination of CT + RT and 50 % CT alone. Five-year overall survival (OS) and progression-free survival (PFS) rates were 39 % and 33 %. Complete remission (CR) rates were significantly higher when using CT + RT (90 %) versus CT alone (33 %) (p < 0.0001). For early-stage disease, CR rates were 37 % for CT alone versus 100 % for CT + RT. Quality of response was significantly associated with survival, with 5-year OS being 80 % for CR patients versus 0 % for progressive disease patients (p  <  0.01). Conclusion Early RT concomitantly or sequentially with CT led to improved patient outcomes, with quality of initial response being the most important prognosticator for 5-year OS.

Background Expression of SRY [sex-determining region Y]-box11 (SOX11) is specific to mantle cell lymphoma (MCL) and contributes, in conjunction with immunoglobulin variable heavy chain gene mutation status, to the identification of two forms of this disease. Methods The aim of this report was firstly, to design an easy and suitable RT-qPCR method to quantify SOX11 mRNA expression in mantle cell lymphoma and other B cell malignancies with the proper reference gene; secondly, to define the best threshold of relative quantity of SOX11 mRNA in order to reach the best compromise between sensitivity and specificity. Results For best discrimination of MCL and non-MCL groups we determined an area under the curve (AUC) of 0.9750 and a threshold of 1.76 with 100% sensitivity and 88% specificity. AUC and threshold values of respectively 0.91/1.346 [87% sensitivity, 80% specificity] and 0.9525/1.7120 [100% sensitivity, 88% specificity] for GAPDH and RPLP0 respectively denote that the RPLP0 reference gene alone is sufficient for PCR housekeeping gene. Conclusion This work describes an RT-qPCR assay for SOX11 expression in order to better characterize MCL at diagnosis. Further studies on larger cohorts are needed to evaluate this molecular tool, especially for the follow-up of minimal residual disease.

Among 15 patients with relapsed ALCL after the failure of brentuximab vedotin therapy, the ALK inhibitor brigatinib led to a complete response in 73%, and progression-free survival at 2 years was 73%.