Summary
Autologous hematopoietic stem cell transplant (ASCT) is the standard curative treatment for patients with high‐risk relapsed/refractory Hodgkin lymphoma (R/R HL). The AETHERA study showed ...survival gain with Brentuximab Vedotin (BV) maintenance after ASCT in BV‐naive patients, which was recently confirmed in the retrospective AMAHRELIS cohort, including a majority of BV‐exposed patients. However, this approach has not been compared to intensive tandem auto/auto or auto/allo transplant strategies, which were used before BV approval. Here, we matched BV maintenance (AMAHRELIS) and tandem SCT (HR2009) cohorts, and observed that BV maintenance was associated with better survival outcome in patients with HR R/R HL.
Introduction
Patients with relapsed/refractory Hodgkin lymphoma (R/R HL) experience high response rates upon anti-PD1 therapy. In these patients, the optimal duration of treatment and the risk of ...relapse after anti-PD1 discontinuation are unknown.
Methods
We retrospectively analyzed patients with R/R HL who responded to anti-PD1 monotherapy and discontinued the treatment either because of unacceptable toxicity or prolonged remission. A machine learning algorithm based on 17 candidate variables was trained and validated to predict progression-free survival (PFS) landmarked at the time of discontinuation of anti-PD1 therapy.
Results
Forty patients from 14 centers were randomly assigned to training (n = 25) and validation (n = 15) sets. At the time of anti-PD1 discontinuation, patients had received treatment for a median duration of 11.2 (range, 0—time to best response was not statistically significant in discriminating patients with PFS lesser or greater than 12 months). Considering PFS status as a binary variable (alive or dead) at a specific time point (12 months) is convenient, intuitive and allows for comparing the value of potential predicting variables in these two groups of patients. Nonetheless, this approach has two drawbacks: first, it binarizes outcome; second, it excludes patients alive with a time to last follow up lesser 12 months. Therefore, it is less powerful to demonstrate statistically significant association with PFS even if it exists 5 months. Patients discontinued anti-PD1 treatment either because of prolonged remission (N = 27, 67.5%) or unacceptable toxicity (N = 13, 32.5%). Most patients were in CR (N = 35, 87.5%) at the time of anti-PD1 discontinuation. In the training set, the machine learning algorithm identified that the most important variables to predict PFS were patients’ age, time to best response, and presence or absence of CR. The performance observed in the training set was validated in the validation set.
Conclusion
In this pilot, proof of concept study using a machine learning algorithm, we identified biomarkers capable of predicting the risk of relapse after anti-PD1 discontinuation (age, time to best response, quality of response). Once confirmed, these simple biomarkers will represent useful tools to guide the management of these patients.
Abstract
Background and Aims
The prognosis of lymphoma that occurs in patients with inflammatory bowel disease IBD is poorly known.
Methods
A multicentre retrospective cohort analysis was done in ...seven French tertiary centres from 1999 to 2019. Only lymphoma occurring in patients with previous established diagnosis of IBD were analysed. The primary outcome was progression-free survival at 3 years.
Results
A total of 52 patients male 65%, Crohn’s disease 79%, median age 48.3 years, median duration of IBD 10.1 years were included, of whom 37 had been previously exposed to immunosuppressants and/or biologics for at least 3 months and 20 had primary intestinal lymphomas. The lymphoma histological types were: diffuse large B cell lymphomas N = 17, Hodgkin lymphomas N = 17, indolent B cell lymphomas N = 12, and others including T cell lymphomas, mantle cell lymphomas, and unclassifiable B cell lymphoma N = 6. The median follow-up after lymphoma was 5.1 years (interquartile range IQR 4–7.8). Progression-free survival at 3 years was 85% in the overall population (95% confidence interval CI 75%–96%) with no significant difference between the exposed and unexposed group, 79% for patients exposed to immunosuppressants and/or biologics 95% CI 67%–94%, and 83% for patients diagnosed with primary intestinal lymphoma 95% CI 67%–100%. No relapse of IBD has been observed during chemotherapy. The IBD relapse rate at the end of the last chemotherapy cycle was 23% at 3 years 95% CI 11%-39% in the overall population.
Conclusions
In this large cohort, the prognosis for lymphomas occurring in IBD appears to be good and similar to what is expected, irrespective of the exposure to biologics and/or immunosuppressants.
Hodgkin lymphoma is a highly curable malignancy involving lymph nodes and the lymphatic system. Even at late stage disease, about 70% of patients will be cured with standard first line therapy. For ...patients who experience relapse or refractory classical Hodgkin lymphoma, the standard treatment option is high-dose chemotherapy followed by autologous stem cell rescue or transplant. However about 50% of patients will have recurrence after high-dose chemotherapy followed by autologous stem cell rescue or transplantation and have worse prognosis with median overall survival of 32% at 5 years. The anti-PD1 checkpoints inhibitors pembrolizumab and nivolumab have remarkably improved outcomes of patients with relapse of refractory classical Hodgkin lymphoma after high-dose chemotherapy followed by autologous stem cell rescue or transplantation. On the other hand, radiotherapy is an entire component of salvage therapy and its efficacy is now well established in term of local disease control in sites of relapsed or refractory Hodkin lymphoma. Defining the optimal modality and timing of radiotherapy as these new agents arrive is a challenge. An interesting approach is the combination of radiotherapy with checkpoint inhibitor and the possibility of stopping the treatment when complete response is achieved. We add to the literature two new cases of combination of radiotherapy with immunotherapy in patients who relapsed after high-dose chemotherapy followed by autologous stem cell rescue or transplantation and consolidation with brentuximab vedotin, resulting in excellent outcomes.
Le lymphome de Hodgkin est une maladie des ganglions et du système lymphatique hautement curable. Même s’il est évolué, environ 70 % des patients seront guéris avec une chimiothérapie standard de première ligne. Pour les patients atteints d’un lymphome de Hodgkin classique en rechute ou réfractaire, le traitement standard repose sur une chimiothérapie de haute dose suivie d’une autogreffe de cellules souches hématopoïétiques. Cependant, environ 50 % des lymphomes récidiveront après autogreffe et auront un pronostic plus défavorable, avec une probabilité de survie globale médiane de 32 % à 5 ans. Les inhibiteurs des checkpoints immunitaires anti-PD1 (programmed cell death 1), pembrolizumab et nivolumab, ont amélioré remarquablement le pronostic des lymphomes de Hodgkin en récidive après intensification-autogreffe. D’autre part, la radiothérapie est un composant à part entière de la stratégie de sauvetage et son efficacité est maintenant bien établie en termes de contrôle local des sites de récidives. Définir les modalités et le timing optimaux de la radiothérapie à l’arrivée de ces nouvelles immunothérapies est un défi. Une approche intéressante consiste à combiner la radiothérapie avec les inhibiteurs de checkpoints et la possibilité d’arrêter le traitement quand une réponse complète est obtenue. Nous ajoutons à la littérature deux nouveaux cas de combinaison de radiothérapie et d’immunothérapie chez des patients en situation de rechute après intensification-autogreffe et consolidation par brentuximab vedotin, conduisant à d’excellents résultats.
The Hodgkin's Lymphoma Committee of the Lymphoma Study Association (LYSA) gathered in 2012 to prepare guidelines on the management of transplant-eligible patients with relapsing or refractory ...Hodgkin's lymphoma. The working group is made up of a multidisciplinary panel of experts with a significant background in Hodgkin's lymphoma. Each member of the panel of experts provided an interpretation of the evidence and a systematic approach to obtain consensus was used. Grades of recommendation were not required since levels of evidence are mainly based on phase II trials or standard practice. Data arising from randomized trials are emphasized. The final version was endorsed by the scientific council of the LYSA. The expert panel recommends a risk-adapted strategy (conventional treatment, or single/double transplantation and/or radiotherapy) based on three risk factors at progression (primary refractory disease, remission duration < 1 year, stage III/IV), and an early evaluation of salvage chemosensitivity, including (18)fluorodeoxy glucose-positron emission tomography interpreted according to the Deauville scoring system. Most relapsed or refractory Hodgkin's lymphoma patients chemosensitive to salvage should receive high-dose therapy and autologous stem-cell transplantation as standard. Efforts should be made to increase the proportion of chemosensitive patients by alternating non-cross-resistant chemotherapy lines or exploring the role of novel drugs.
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