Primary refractory follicular lymphoma: a poor outcome entity with high risk of transformation to aggressive B cell lymphoma

Alonso‐Álvarez, Sara; Manni, Martina; Montoto, Silvia; Sarkozy, Clémentine; Morschhauser, Franck; Wondergem, Mariëlle J.; Guarini, Attilio; Magnano, Laura; Alcoceba, Miguel; Galimberti, Sara; Silva, Maria Gomes da; Holte, Harald; Zucca, Emanuele; Lockmer, Sandra; Aurer, Igor; Marcheselli, Luigi; Stepanishyna, Yana; Barrigón, María Dolores Caballero; Salles, Gilles; Federico, Massimo

doi:10.1016/j.ejca.2021.08.005

Cited by 7 publications

(4 citation statements)

References 27 publications

(39 reference statements)

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“…Lymphoma is one of the common malignant hematological diseases [7] . Unfortunately, treatment reaction to conventional radiotherapy and chemotherapy is not ideal, the disease control and prognosis are poor in high-risk and relapse, refractory patients [8][9][10] . Recurrence and drug resistance seriously limit the further improvement of efficacy [11] .…”

Section: Results and Disscutionmentioning

confidence: 99%

Comparison of Efficacy and Safety of BEAC BEAM and Be-EAM Conditioning Regimens Prior to Autologous Stem Cell Transplantation in Lymphoma

Chen¹,

Jiang²,

He³

et al. 2022

IJPS

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Autologous hematopoietic stem cell transplantation is recommended and significantly improved the prognosis of lymphoma patients. However, the preferred conditioning regimen prior to autologous hematopoietic stem cell transplantation is still a controversial topic. Current experiment was aim to explore the efficacy and safety of BEAC (carmustine, etoposide, cytarabine and cyclophosphamide), BEAM (carmustine, etoposide, cytarabine and melphalan) and Be-EAM (bendamustine, cytarabine, etoposide and melphalan) preparative regimens in lymphoma patients who underwent autologous hematopoietic stem cell transplantation. 19 lymphoma cases were enrolled and followed-up for 13 mo, 6 cases were treated with BEAC, 5 cases were treated with BEAM and 8 cases were treated with Be-EAM. We found the median progression free survival was 23 mo in BEAC group, but the progression free survival and the overall survival in the other 2 groups had not been reached due to the short follow-up time. The median of patients achieved neutrophil and platelet engraftment were 12.500 and 15.167 d in BEAC group, 11.200 and 14.000 d in BEAM group and Be-EAM cohort were 11.250 and 11.750 d. Statistically differences on platelet engraftment were observed in Be-EAM comparing with BEAC and BEAM regimens. Additionally, the volume of platelet transfusion in the Be-EAM group was the least in three groups. The main adverse events included bone marrow suppression, fever, mucositis, nausea and vomiting and all of them were acceptable. The efficacy and safety were favorable in lymphoma patients who received conditioning treatment with Be-EAM comparing with BEAC and BEAM regimens. The Be-EAM regimen has a shorter hospital stay, faster hematopoietic reconstitution, fewer platelet infusions and the superiority of storage conditions and drug cost of bendamustine, the Be-EAM regimen could be a potential optimistic option for lymphoma conditioning treatment.

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Section: Results and Disscutionmentioning

confidence: 99%

Comparison of Efficacy and Safety of BEAC BEAM and Be-EAM Conditioning Regimens Prior to Autologous Stem Cell Transplantation in Lymphoma

Chen¹,

Jiang²,

He³

et al. 2022

IJPS

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“… 4 An additional population of concern is primary refractory, these patients also have a worse prognosis. 5 …”

Section: Introductionmentioning

confidence: 99%

Targeted Therapy for Relapsed/Refractory Follicular Lymphoma: Focus on Clinical Utility of Tazemetostat

Raychaudhuri¹,

Ujjani²

2022

OTT

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The management of follicular lymphoma (FL) in the relapsed and refractory setting is challenging and an area of ongoing investigation. Epigenetic dysregulation has recently been shown to be a hallmark of FL. Mutations in histone-modifying genes are likely early, driver events in FL pathogenesis, and so are attractive targets to drug. Gain-of-function mutations in the histone methyltransferase EZH2 are common in FL and maintained through disease evolution. With mounting data supporting a critical role for EZH2 as an oncogenic driver for FL, the small molecule inhibitor, tazemetostat, was developed. Tazemetostat has shown promising activity in preclinical models and early phase trials. Importantly, responses were seen in patients with high-risk features. Based on these data, tazemetostat was approved in the US in 2020 for EZH2 mut patients with FL who had received at least two prior lines of systemic therapy, or for EZH2 wt patients without alternative treatment options. Here, we will review the biology of FL as it pertains to tazemetostat, the available clinical trial data, and future directions for this new therapy.

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“…In fact, both POD24 9 and POD30 6 patients have been reported to have a five‐year OS between 41% and 50% and a 10‐year OS of 53% respectively. These subgroups, which account for around 20% of all FL cases, have been allocated to the high‐risk categories of various prognostic indexes (i.e., FLIPI, FLIPI‐2, PRIMA‐PI, m7‐FLIPI and FLEX) at the time of lymphoma diagnosis, 15–20 and are associated to a higher risk of histological transformation (HT) 21,22 . However, tools for identifying at diagnosis individual patients who will become POD24 are not well defined.…”

Section: Introductionmentioning

confidence: 99%

“…These subgroups, which account for around 20% of all FL cases, have been allocated to the high-risk categories of various prognostic indexes (i.e., FLIPI, FLIPI-2, PRIMA-PI, m7-FLIPI and FLEX) at the time of lymphoma diagnosis, [15][16][17][18][19][20] and are associated to a higher risk of histological transformation (HT). 21,22 However, tools for identifying at diagnosis individual patients who will become POD24 are not well defined. Moreover, this group of poor prognosis is heterogeneous and even after adjusting for the Follicular Lymphoma International Prognostic Index (FLIPI) score, early relapse confers an increased risk of death by itself.…”

Section: Introductionmentioning

confidence: 99%

Early progression in follicular lymphoma in the absence of histological transformation or high‐risk Follicular Lymphoma International Prognostic Index still has a favourable outcome

et al. 2022

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Although follicular lymphoma (FL) patients relapsing within 24 months after firstline treatment (POD24) have a poor prognosis, some cases show notable survival after first relapse (SF1R). We aimed to characterize the POD24 FL population and to identify the main prognostic factors at progression. We selected 162 POD24 patients (80F; median age at first relapse 59 years) from a cohort of 1067 grades 1-3a FL-treated patients. The remaining 905 patients treated with first-line immunochemotherapy and diagnosed during the same period were used to compare outcomes in terms of survival. After a median follow-up of 11.0 years, 96 patients died (10y-SF1R of 40%). Age over 60 years (p < 0.001), high lactate dehydrogenase (LDH) (p < 0.001), haemoglobin (Hb) less than 120 g/L (p < 0.001), advanced stage (p < 0.001), high-risk Follicular Lymphoma International Prognostic Index (FLIPI) (p < 0.001), histological transformation (HT) (p < 0.001) and reaching less than complete response (CR) after salvage therapy (p < 0.001), predicted poor SF1R at relapse. In multivariate analysis only high-risk FLIPI and HT maintained prognostic significance for SF1R. POD24patients not transformed and with low/intermediate FLIPI at relapse behaved better than the remaining cases. POD24 patients showed an excess mortality of 38% compared to the general population. Although outcome of POD24 FL patients is poor, a considerable group of them (low/intermediate FLIPI and not transformed at first relapse) behave better.

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Primary refractory follicular lymphoma: a poor outcome entity with high risk of transformation to aggressive B cell lymphoma

Cited by 7 publications

References 27 publications

Comparison of Efficacy and Safety of BEAC BEAM and Be-EAM Conditioning Regimens Prior to Autologous Stem Cell Transplantation in Lymphoma

Comparison of Efficacy and Safety of BEAC BEAM and Be-EAM Conditioning Regimens Prior to Autologous Stem Cell Transplantation in Lymphoma

Targeted Therapy for Relapsed/Refractory Follicular Lymphoma: Focus on Clinical Utility of Tazemetostat

Early progression in follicular lymphoma in the absence of histological transformation or high‐risk Follicular Lymphoma International Prognostic Index still has a favourable outcome

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