scholarly journals SYSTEMIC FRONT LINE THERAPY OF FOLLICULAR LYMPHOMA: WHEN, TO WHOM AND HOW

2016 ◽  
Vol 8 ◽  
pp. e2016062 ◽  
Author(s):  
Francesca Pavanello ◽  
Sara Steffanoni ◽  
Michele Ghielmini ◽  
Emanuele Zucca

The natural history of follicular lymphoma is usually characterized by an indolent course with a high response rate to the first line therapy followed by recurrent relapses, with a time to next treatment becoming shorter after each subsequent treatment line. More than 80% of patients have advanced stage disease at diagnosis. The time of initiation and the nature of the treatment is mainly conditioned by symptoms, tumor burden, lymphoma grading, co-morbidities and patients preference. A number of clinical and biological factors have been determined to be prognostic in this disease, but the majority of them could not show to be predictive of response to treatment, and therefore can’t be used to guide the treatment choice. CD20 expression is the only predictive factor recognized in the treatment of FL and justifies the use of “naked” or “conjugated” anti-CD20 monoclonal antibodies as single agent or in combination with chemo- or targeted therapy. Nevertheless, as this marker is almost universally found in FL, it has little role for the choice of treatment. The outcome of patients with FL improved significantly in the last years, mainly due to the widespread use of rituximab, autologous and allogeneic transplantation in young and fit relapsed patients, the introduction of new drugs and the improvement in diagnostic accuracy and management of side effects. Agents as new monoclonal antibodies, immuno-modulating drugs and target therapy have recently been developed and approved for the relapsed setting, while studies to evaluate their role in first line treatment are still ongoing. Here we report our considerations on first line treatment approach and on the potential factors which could help in the choice of therapy.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1014-1014
Author(s):  
Marek Trneny ◽  
Robert Pytlik ◽  
David Belada ◽  
Katerina Kubackova ◽  
Milada Jankovska ◽  
...  

Abstract Follicular lymphoma is considered to be incurable disease, although rituximab introduction into the first line therapy has changed the outcome of the patients. Repeated relapses are observed and it is accepted, that each subsequent remission in the same patient has significantly shorter duration compared to the previous one (Gallagher, JCO 1986). We have addressed this question in the group of patients diagnosed and treated in the rituximab era. The interval 1999 till 2002 was chosen because in this time rituximab was already labeled for relapse treatment, but not for the first line treatment. Patients and method: Patients diagnosed as FL gr I, II, IIIa (central pathology review) and reported in the 6 centers during the period 1999–2002 were included into the analysis. The cohort consisted out of 176 pts. Median age at the 57.5 y(22–93), B symptoms were observed in 40 pts (2 missing), clinical stage (CS) I had 16 pts, II 32 pts, III 28 pts and IV 95 pts, PS WHO ≥ 2 in 25 pts(four missing), elevated LDH >n 60 pts (8 missing). FLIPI was estimated as poor risk in 52, intermediate risk in 46 and good risk in 66 pts. (13 missing). Median follow up is 7.5 years. Results: Ninety eight (55%) pts experienced 1st progression and 9 deaths without progression, 36 pts 2nd progression and 14 deaths w/o progression, 15 pts 3 rd progression and 6 death w/o progression and 9 pts 4th progression, therefore 176 were evaluable for 1st response, 98 pts were evaluable for duration of 2nd response, 36 for 3rd resp, 15 for 4th response. Median age was 57.5y at dg, 59y at 1st, 64y at 2nd, 66y at 3rd and 77y at 4th progression. The treatment data for the first line: 175 pts evaluable, 3 pts watch and wait (WW), anthracyclin based chemotherapy (A-th) 76%, fludarabine based chemotherapy (F-th) 5.2%, rituximab (R) 28.5%, radiotherapy (RT) 19.1%, ASCT 9.3%. 2nd line therapy: 93 pts available, WW 5pts, A-th 26%, F-th 13.6%, R 70.5%, RT 8.0%, ASCT 20.5%, AlloSCT 2.3%, 3rd line therapy: 35 pts evaluable, WW 3 pts, A-th 9.4%, F-th 28%, R 65.6%, RT 31.3%, ASCT and AlloSCT both 3.1%, 4th line therapy: 10 pts evaluable, WW 1 pt, A-th 1 pt, F-th 3 pts, R 7 pts, RT 3 pts. The significant increase in the relative number of rituximab treated pts in the subsequent treatment lines was observed. Median survival for the all pts PFS was 40 months, median OS not reached (79 month at 7 y). The medians of the time to progression (TTP) in subsequent responses (deaths w/o progression were excluded) were as follows: TTP1 49m, TTP2 43 m, TTP3 52m and TTP4 11m. There was no signifiant difference observed between TTP1, TTP2 and TTP3, but due the the very short TTP4 the overall significance was 0.05. Comparison of the PFS of subsequent lines revealed median PFS1 40 months, PFS2 30 months, PFS3 14 m and PFS4 11m. The difference between PFS1 and PFS2 was not significant, the subsequent PFS were significantly shorter for PFS3 and PFS 4 compared to the previous ones (p<0.05). Conclusion: The present analysis demonstrates that introduction of rituximab in the treatment of relapses led to the same TTP after 1st, 2nd or 3rd line of treatment, and the same PFS after the first and 2nd line therapy. The introduction of the efficient treatment modality - rituximab - into the relapse treatment has changed the concept, that each subsequent response have to have significantly shorter duration. This is important for understanding of natural history of the indolent disease such as follicular lymphoma. The reanalysis however needs to be done on the cohort of patients treated with rituximab as part of the first line treatment in the future with the sufficient follow up Supported by grant IGA MZ CR number NR/9453-3.


Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3745
Author(s):  
Hélène Vellemans ◽  
Marc P. E. André

Hodgkin lymphoma (HL) is a lymphoid-type hematologic disease that is derived from B cells. The incidence of this lymphoid malignancy is around 2–3/100,000/year in the western world. Long-term remission rates are linked to a risk-adapted approach, which allows remission rates higher than 80%. The first-line treatment for advanced stage classical HL (cHL) widely used today is doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc) chemotherapy. Randomized studies comparing these two regimens and a recently performed meta-analysis have demonstrated consistently better disease control with BEACOPPesc. However, this treatment is not the standard of care, as there is an excess of acute hematological toxicities and therapy-related myeloid neoplasms. Moreover, there is a recurrent controversy concerning the impact on overall survival with this regimen. More recently, new drugs such as brentuximab vedotin and checkpoint inhibitors have become available and have been evaluated in combination with doxorubicin, vinblastine, and dacarbazine (AVD) for the first-line treatment of patients with advanced cHL with the objective of tumor control improvement. There are still major debates with respect to first-line treatment of advanced cHL. The use of positron emission tomography-adapted strategies has allowed a reduction in the toxicity of chemotherapy regimens. Incorporation of new drugs into the treatment algorithms requires confirmation.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuejun He ◽  
Jijun You ◽  
Haibing Ding ◽  
Zhisheng Zhang ◽  
Lin Cui ◽  
...  

Abstract Background Vascular mimicry (VM) was associated with the prognosis of cancers. The aim of the study was to explore the association between VM and anticancer therapy response in patients with lung adenocarcinoma. Methods This was a single-center retrospective study of patients with lung adenocarcinoma between March 1st, 2013, to April 1st, 2019, at the Second People’s Hospital of Taizhou City. All included patients were divided into the VM and no-VM groups according to whether VM was observed or not in the specimen. Vessels with positive PAS and negative CD34 staining were confirmed as VM. The main outcome was progression-free survival (PFS). Results Sixty-six (50.4%) patients were male. Eighty-one patients received chemotherapy as the first-line treatment, and 50 patients received TKIs. Forty-five (34.4%) patients were confirmed with VM. There was no difference regarding the first-line treatment between the VM and no-VM groups (P = 0.285). The 86 patients without VM had a median PFS of 279 (range, 90–1095) days, and 45 patients with VM had a median PFS of 167 (range, 90–369) days (P < 0.001). T stage (hazard ratio (HR) = 1.37, 95% confidence interval (CI): 1.10–1.71), N stage (HR = 1.43, 95%CI: 1.09–1.86), M stage (HR = 2.85, 95%CI: 1.76–4.61), differentiation (HR = 1.85, 95%CI: 1.29–2.65), therapy (HR = 0.32, 95%CI: 0.21–0.49), VM (HR = 2.12, 95%CI: 1.33–3.37), and ECOG (HR = 1.41, 95%CI: 1.09–1.84) were independently associated with PFS. Conclusion The benefits of first-line TKIs for NSCLC with EGFR mutation are possibly better than those of platinum-based regimens in patients without VM, but there is no difference in the benefit of chemotherapy or target therapy for VM-positive NSCLC harboring EGFR mutations.


2017 ◽  
Vol 53 (3) ◽  
pp. 139-146
Author(s):  
Urszula Rychlik ◽  
Ewa Wójcik ◽  
Jadwiga Tarapacz ◽  
Katarzyna Brandys ◽  
Zofia Stasik ◽  
...  

Introduction: The aim of the study was to assess the prognostic value of indicators calculated on the basis of initial hematology test results of neutrophil, lymphocyte, monocyte and platelet counts (NLR – neutrophil-to-lymphocyte ratio, LMR – lymphocyte-to-monocyte ratio, PLR – platelet-to-lymphocyte ratio) in patients with ovarian cancer and their compliance with the overall response to treatment. Materials and methods: Hematological tests were performed before first course of first-line chemotherapy in 145 patients with ovarian cancer. Response to treatment was assessed according to the RECIST1.1 criteria in all patients. Results: After the completion of first-line treatment, 70 (48.3%) patients had a complete response (CR) to the therapy. In this group, progression of disease occurred in 22 (31.4%) patients during 12 months of follow-up. In the CR group with progression, 17 (77.2%) presented high NLR and PLR levels. Among 48 (68.6%) patients with CR without progression after 12 months of follow-up, high levels of NLR and PLR were observed in 21 (43.8%) and 17 (35.4%) of them, respectively. Low LMRs were observed in 16 (72.7%) patients with progression and 16 (33.3%) without progression. Conclusion: High levels of NLR and PLR and low levels of LMR before treatment seems to predict 12-month disease progression in patients with complete response to first-line treatment.


1995 ◽  
Vol 13 (11) ◽  
pp. 2722-2730 ◽  
Author(s):  
B L Weber ◽  
C Vogel ◽  
S Jones ◽  
H Harvey ◽  
L Hutchins ◽  
...  

PURPOSE We evaluated single-agent intravenous (IV) vinorelbine as first- and second-line treatment for advanced breast cancer (ABC) in patients who were not resistant to anthracyclines. Objective tumor response (TR) and toxicity were assessed. PATIENTS AND METHODS A total of 107 women were enrolled onto this multicenter, nonrandomized, open-label phase II study. Patients were stratified into first- and second-line treatment groups, based on prior treatment history. Vinorelbine was initially given at 30 mg/m2/wk, with dose modification for toxicity as indicated. Therapy was continued until disease progression or severe toxicity mandated withdrawal or until the patient asked to be removed from the study. RESULTS The objective response rate for all patients was 34% (95% confidence interval [CI], 25% to 44%): 35% (95% CI, 23% to 48%) for first-line patients and 32% (95% CI, 20% to 47%) for second-line patients. Nine first-line and three second-line patients obtained a complete response (CR). The median duration of objective response was 34 weeks in both groups. The overall survival durations of first- and second-line patients were 67 weeks and 62 weeks, respectively. Granulocytopenia was the predominant dose-limiting toxicity. Two patients died on study as a result of granulocytopenic sepsis. CONCLUSION Single-agent vinorelbine is an effective and well-tolerated agent for first- and second-line therapy of ABC. The results of this study confirm the findings of similar international trials and suggest vinorelbine should be considered a valid treatment option for patients with ABC and a potential component in future combination regimens for this disease.


2019 ◽  
Vol 217 (1) ◽  
Author(s):  
Immo Prinz ◽  
Inga Sandrock ◽  
Ulrich Mrowietz

The IL-17 cytokine family comprising IL-17A to IL-17F and receptor subunits IL-17RA to IL-17RE represents a genetically ancient intercellular network regulating local tissue homeostasis. Its pivotal role in antifungal defense and its central position in the pathogenesis of inflammatory diseases including psoriasis were discovered only relatively late in the early 2000s. Since the connection of dysregulated IL-17 and psoriasis pathogenesis turned out to be particularly evident, a number of monoclonal antibodies targeting IL-17 pathways have been approved and are used as first line treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis, and further agents are currently in clinical development.


Blood ◽  
2020 ◽  
Vol 135 (24) ◽  
pp. 2133-2136 ◽  
Author(s):  
Christopher R. Flowers ◽  
John P. Leonard ◽  
Nathan H. Fowler

Abstract Lenalidomide is an immunomodulatory drug approved in the United States for use with rituximab in patients with relapsed/refractory follicular lymphoma. We reviewed data from trials addressing the safety and efficacy of lenalidomide alone and in combination with rituximab as a first-line therapy and as a treatment of patients with relapsed/refractory follicular lymphoma. Lenalidomide-rituximab has been demonstrated to be an effective chemotherapy-free therapy that improves upon single-agent rituximab and may become an alternative to chemoimmunotherapy.


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