Allogeneic hematopoietic cell transplantation (allo-HCT) is indicated for patients with relapsed or refractory Hodgkin lymphoma (HL). Although long-term disease control can be achieved, relapse is ...still frequent. The programmed cell death protein 1 (PD-1) pathway-blocking antibody nivolumab has shown substantial therapeutic activity and an acceptable safety profile in patients with relapsed or refractory HL who did not receive allo-HCT. However, PD-1 blocking strategy can increase the risk of graft-versus-host disease (GVHD) in murine models. We retrospectively assessed the efficacy and toxicity of nivolumab as a single agent in 20 HL patients relapsing after allo-HCT. GVHD occurred in 6 patients (30%) after nivolumab initiation. All 6 patients had prior history of acute GVHD. The patients with nivolumab-induced GVHD were managed by standard treatment for acute GVHD. Two patients died as a result of GVHD, 1 of progressive disease and 1 of complications related to a second allo-HCT. Overall response rate was 95%. At a median follow-up of 370 days, the 1-year progression-free survival rate was 58.2% (95% CI, 33.1%-76.7%) and the overall survival rate was 78.7% (95% CI, 52.4%-91.5%). Among 13 patients still in response, 6 received a single dose of nivolumab and 7 remain on nivolumab. Compared with standard options for this indication, our results show that nivolumab is effective with an acceptable safety profile.
•PD-1 blockade with nivolumab provides durable disease control after allo-HCT.•PD-1 blockade with nivolumab after allo-HCT is associated with 30% acute GVHD.
Anti‐PD‐1 therapy provides high response rates in Hodgkin lymphoma (HL) patients who have relapsed or are refractory (R/R) to autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV), ...but median progression free survival (PFS) is only one year. The efficacy of treatment following anti‐PD‐1 is not well known. We retrospectively investigated the efficacy of salvage therapies for unsatisfactory response to anti‐PD‐1 therapy, assessed by PET‐CT according to the Lugano criteria, in 30 R/R HL patients. Patients were highly pretreated before anti‐PD‐1 (70% received ASCT and 93% BV). Unsatisfactory responses to anti‐PD1 therapy were progressive disease (PD) (n = 24) and partial response (PR) (n = 6). For the 24 PD patients, median anti‐PD‐1 related PFS was 7.5 months (95%CI, 5.7‐11.6); 17 received subsequent CT alone (Group 1) and 7 received CT in addition to anti‐PD‐1 (Group 2). 16/24 patients (67%) obtained an objective response. In the 15 patients treated with the same CT, twelve obtained PR or complete response (CR). In Group 1, there were 7 CR (41%), 3 PR (18%), and 7 PD (41%). In Group 2, there were 4 CR (57%), 2 PR (29%), and 1 SD (14%). No unexpected toxicity was observed. Six patients who achieved response proceeded to allogeneic SCT. With a median follow‐up of 12.1 months (7‐14.7), the median PFS following the initiation of CT was 11 months (95% CI 6.3‐not reached) and the median of overall survival was not reached. These observations in highly pretreated HL patients suggest that anti‐PD‐1 therapy might re‐sensitize tumor cells to CT.
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.
Patients with lymphoma are immunocompromised because of the disease per se and its treatments. We aimed to describe the characteristics of patients with lymphoma hospitalized for Coronavirus Disease ...2019 (Covid-19) and to analyze pre-Covid-19 determinants of mortality.
This retrospective multicentric cohort study used the Programme de Médicalisation des Systèmes d'Information database to identify all adult patients with lymphoma, hospitalized for Covid-19 in March and April 2020, in 12 hospitals of three French regions with pandemic outbreaks. The characteristics of lymphoma and Covid-19 were collected from medical charts.
Eighty-nine patients were included. The median age was 67 years (range, 19–92), 66% were male and 72% had a comorbidity. Most patients had B-cell non-Hodgkin lymphoma (86%) and had received a lymphoma treatment within one year (70%). With a median follow-up of 33 days from admission, 30-day overall survival was 71%, (95% confidence interval, 62–81%). In multivariable analysis, having an age ≥ 70 years (hazard ratio 2·87, 1·20–6·85, p = 0·02) and relapsed/refractory lymphoma (hazard ratio 2·54, 1·14–5·66, p = 0·02) were associated with mortality. Recent bendamustine treatment (n = 9) was also pejorative (hazard ratio 3·20, 1·33–7·72, p = 0·01), but was strongly associated with relapsed/refractory lymphoma. Remarkably, 30-day overall survival for patients < 70 years of age without relapsed/refractory lymphoma was 88% (78% - 99%).
Thirty-day mortality was associated with being older and relapsed/refractory lymphoma. Survival of patients younger than 70 years without relapsed/refractory lymphoma was comparable to that of the general population.
There have been no specific funds to run this study.
Immunotherapy (IT) is a major therapeutic strategy for lymphoma, significantly improving patient prognosis. IT remains ineffective for a significant number of patients, however, and exposes them to ...specific toxicities. The identification predictive factors around efficacy and toxicity would allow better targeting of patients with a higher ratio of benefit to risk. PRONOSTIM is a multicenter and retrospective study using the Clinical Data Warehouse (CDW) of the Greater Paris University Hospitals network. Adult patients with Hodgkin lymphoma or diffuse large-cell B lymphoma treated with immune checkpoint inhibitors or CAR T (Chimeric antigen receptor T) cells between 2017 and 2022 were included. Analysis of covariates influencing progression-free survival (PFS) or the occurrence of grade ≥3 toxicity was performed. In total, 249 patients were included. From this study, already known predictors for response or toxicity of CAR T cells such as age, elevated lactate dehydrogenase, and elevated C-Reactive Protein at the time of infusion were confirmed. In addition, male gender, low hemoglobin, and hypo- or hyperkalemia were demonstrated to be potential predictive factors for progression after CAR T cell therapy. These findings prove the attractiveness of CDW in generating real-world data, and show its essential contribution to identifying new predictors for decision support before starting IT.
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.
Patients (pts) with asymptomatic low‐burden follicular lymphoma (FL) are usually observed at diagnosis. Time to lymphoma treatment (TLT) initiation can however be very heterogeneous and risk factors ...of progression are poorly studied. Our study evaluated 201 pts with grade 1–3a low‐tumor burden FL diagnosed in four French centers between 2010 and 2020 and managed by a watch and wait strategy in real‐life settings. After a median follow‐up of 4.8 years, the median TLT was 4.2 years (95% confidence interval, 3.1‐5.5). On multivariate analysis, elevated lactate dehydrogenase (hazard ratio HR = 2.2; P = 0.02), more than 4 nodal areas involved (HR = 1.7; P = 0.02) and more than 1 extranodal involvement (HR = 2.7; P = 0.01) were identified as independent predictors of TLT. The median TLT was 5.8 years for pts with no risk factor, 2.4 years for 1 risk factor, and 1.3 years for >1 risk factors (P < 0.01). In a subanalysis of 75 pts staged with positron emission tomography‐computed tomography (PET‐CT), total metabolic tumor volume (TMTV) ≥14 cm3 and standardized Dmax (reflecting tumor dissemination) >0.32 m−1 were also associated with shorter TLT (HR = 3.4; P = 0.004 and HR = 2.4; P = 0.007, respectively). In multivariate models combining PET‐CT parameters and clinical variables, TMTV remained independent predictor of shorter TLT. These simple parameters could help to identify FL patients initially observed at higher risk of early progression. The role of PET‐CT (extranodal sites and PET metrics) in low‐burden FL appears promising and warrants further assessment in large cohorts.
Post‐transplant lymphoproliferative disorder (PTLD) is a rare complication of immunosuppression. Sequential treatment is commonly proposed, combining induction with rituximab (R‐induction) followed ...by either continuation of treatment or addition of chemotherapy depending on response. Response to R‐induction, often assessed by CT scan, is a major predictor of overall survival (OS). The aim of the study was to analyze predictive factors of R‐induction response, including total metabolic tumor volume (TMTV), and investigate the role of 18F‐FDG PET/CT in response assessment. This retrospective multicenter study is based on patients with PTLD included in the K‐VIROGREF cohort. Only patients treated by R‐induction with a baseline 18F‐FDG PET/CT were included. Response to R‐induction was assessed by 18F‐FDG PET/CT. The optimal threshold of TMTV for rituximab response was determined using receiver operating characteristic curves. Univariate and multivariate analyses were conducted to identify predictive factors of response. A total of 67 patients were included. Survival characteristics were similar to those previously reported: the complete response rate to R‐induction was 30%, the 3‐year OS estimate was 66%, and the treatment‐related mortality was 4%. The optimal threshold for TMTV to predict R‐induction response was 135 cm3. The response rate to R‐induction was 38% in the 21 patients with TMTV ≥ 135 cm3 and 72% in the 46 patients with TMTV < 135 cm3. TMTV was a significant predictor of response, both at univariate and multivariate analyses (odd ratios = 3.71, P = 0.022). Baseline TMTV is predictive of response to R‐induction. Early assessment of patient response is feasible with 18F‐FDG PET/CT.
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