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Author: Chunlan Qiugui This article is authorized by the author to publish by Yimaitong, please do not reprint without authorization.
In recent years, anthracycline-containing chemotherapy combined with rituximab has improved the prognosis of patients with follicular lymphoma (FL).
However, there is still no cure for FL, and all patients will eventually face relapse or refractory.
Therefore, how to develop a reasonable treatment strategy for patients with relapsed or refractory FL (R/R FL) is particularly important.
This article aims to sort out the treatment principles of R/R FL for your reference.
R/R FL patients need clear details before treatment.
For FL patients, when disease progression or recurrence is suspected, PET/CT scan is recommended, and the lesion site with the highest abnormal uptake value is selected for re-pathological biopsy to rule out aggressive lymphoma transformation .
In addition, for patients with relapsed advanced FL, it is also necessary to determine whether the patient has specific treatment indications.
For patients with low tumor burden and no treatment indications, you can choose to wait and see.
Rescue induction therapy selection strategy for R/R FL patients For limited-stage R/R FL patients, low-dose involved field radiotherapy (ISRT) can be selected.
For patients with systemic R/R FL, the choice of rescue induction therapy depends on the previous treatment plan, the efficacy of the previous treatment, the duration of the previous treatment response, and the time to relapse.
If the patient has an early relapse (<12-24 months), non-cross-resistance re-induction chemotherapy is the first choice, such as CHOP (cyclophosphamide, vincristine, doxorubicin, prednisone) followed by bendammus Ting’s chemotherapy regimen, and vice versa.
Other chemotherapy regimens including fludarabine, platinum-based or alkylating agents are also available.
Should patients with R/R FL use rituximab? If the patient's previous rituximab-containing regimen achieves a duration of remission> 6-12 months, rituximab should be added to the rescue induction therapy.
For patients with R/R FL whose previous treatment is clearly refractory to rituximab or who have previously used rituximab-containing regimens, the duration of remission is less than 6 months, the new anti-CD20 monoclonal antibody Otto can be used Rizumab combined with bendamustine (subsequent maintenance therapy with otuzumab), compared with bendamustine monotherapy, the combination of the two can improve patient progression-free survival (PFS) and overall survival (OS) [1].
The results of clinical studies have shown that in patients with relapsed FL, lenalidomide combined with rituximab (R2) regimen has a significant benefit in terms of patient efficiency and PFS compared with rituximab monotherapy.
OS also has an improvement trend [2].
Therefore, for R/R FL, especially for patients who only get short-term remission after first-line chemotherapy, R2 can be chosen as a rescue induction therapy.
For elderly R/R FL patients with comorbidities who are not suitable for chemotherapy, radioimmunotherapy can be selected.
For R/R FL patients with late recurrence (>24 months), the original induction treatment plan can be adopted, and a more moderate treatment plan can also be adopted, such as the R2 plan.
For patients with high tumor burden and elevated lactate dehydrogenase levels, non-cross-resistance second-line induction therapy can be used, such as bendamustine combined with rituximab.
The results of a phase II clinical study evaluating the phosphoinositide 3-kinase (PI3K) inhibitor idelalisib in the treatment of R/R FL patients confirmed the effective clinical activity of idelalisib, but suffered from treatment-related side effects such as infection, delayed colitis and lung The effect of toxicity [3].
Therefore, it is strongly recommended to conduct anti-infection prevention and cytomegalovirus monitoring when using idelalisib.
In recent years, new methods including B-cell signaling pathway inhibitors and other targeted drugs have shown activity in phase II studies, but so far, their benefits have not been confirmed in randomized phase III studies.
Targeting CD19 chimeric antigen receptor (CAR) T cell therapy can provide long-term remission in some patients with R/R FL.
However, due to its treatment-related toxicity, this method is still only suitable for patients with aggressive lymphoma transformation.
patient.
Consolidation/maintenance treatment strategy for R/R FL patients According to previous research results [4], high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (ASCT) can prolong the PFS of R/R FL patients, and there is a trend to prolong OS.
Therefore, for patients with R/R FL suitable for transplantation, ASCT consolidation therapy should be considered after the salvage induction therapy is effective, especially for the short first remission time (<2-3 years) after the previous treatment with rituximab-containing regimen.
Of patients.
In addition, for the above patients after ASCT consolidation therapy, rituximab maintenance therapy can further improve the patient's PFS [5].
For a very small number of special young R/R FL patients, such as early relapse or refractory patients, and patients with high risk of recurrence or relapse after ASCT, allogeneic hematopoietic stem cell transplantation (Allo-HSCT) with a reduced-dose pretreatment regimen can be considered ) It is expected that the patient will be cured.
A systematic meta-analysis showed [6] that even in R/R FL patients who were rescued induction therapy with a monoclonal antibody-containing regimen, rituximab was subsequently given as maintenance therapy every 3 months (for 2 years) , The patient still has good tolerance, and can significantly prolong the patient’s PFS and OS.
However, for those patients who have received monoclonal antibody maintenance therapy in the first-line treatment, whether the monoclonal antibody maintenance therapy can still be used in the second-line treatment is currently lacking relevant research data, and it is not recommended for the time being.
References: 1.
Cheson BD, Chua N, Mayer J, et al.
Overall survival benefit in patients with rituximab-refractory indolent non-hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN study.
J Clin Oncol.
2018 ;36(22):2259-2266.
2.
Leonard JP, Trneny M, Izutsu K, et al.
AUGMENT: a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma.
J Clin Oncol.
2019 ;37(14):1188-1199.
3.
Gopal AK, Kahl BS, de Vos S, et al.
PI3Kd inhibition by idelalisib in patients with relapsed indolent lymphoma.
N Engl J Med.
2014;370:1008-1018.
4 .
Casulo C, Byrtek M, Dawson KL, et al.
Early relapse of follicular lymphoma after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone defines patients at high risk for death:an analysis from the national LymphoCare study.
J Clin Oncol.
2015;33:2516-2522.
5.
Pettengell R, Schmitz N, Gisselbrecht C, et al.
Rituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma: a prospective randomized trial from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.
J Clin Oncol.
2013;31:1624-1630.
6.
Vidal L, Gafter-Gvili A, Salles G, et al.
Rituximab maintenance for the treatment of patients with follicular lymphoma: an updated systematic review and meta-analysis of randomized trials.
J Natl Cancer Inst.
2011;103:1799-1806.
Stamp "Read the original text", we make progress togetherRituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma: a prospective randomized trial from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.
J Clin Oncol.
2013;31:1624-1630.
6.
Vidal L, Gafter-Gvili A, Salles G, et al.
Rituximab maintenance for the treatment of patients with follicular lymphoma: an updated systematic review and meta-analysis of randomized trials.
J Natl Cancer Inst.
2011;103:1799-1806.
Stamp "Read the original", we make progress togetherRituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma: a prospective randomized trial from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.
J Clin Oncol.
2013;31:1624-1630.
6.
Vidal L, Gafter-Gvili A, Salles G, et al.
Rituximab maintenance for the treatment of patients with follicular lymphoma: an updated systematic review and meta-analysis of randomized trials.
J Natl Cancer Inst.
2011;103:1799-1806.
Stamp "Read the original", we make progress togetherRituximab maintenance for the treatment of patients with follicular lymphoma: an updated systematic review and meta-analysis of randomized trials.
J Natl Cancer Inst.
2011;103:1799-1806.
Stamp "Read the original text", we make progress togetherRituximab maintenance for the treatment of patients with follicular lymphoma: an updated systematic review and meta-analysis of randomized trials.
J Natl Cancer Inst.
2011;103:1799-1806.
Stamp "Read the original text", we make progress together
In recent years, anthracycline-containing chemotherapy combined with rituximab has improved the prognosis of patients with follicular lymphoma (FL).
However, there is still no cure for FL, and all patients will eventually face relapse or refractory.
Therefore, how to develop a reasonable treatment strategy for patients with relapsed or refractory FL (R/R FL) is particularly important.
This article aims to sort out the treatment principles of R/R FL for your reference.
R/R FL patients need clear details before treatment.
For FL patients, when disease progression or recurrence is suspected, PET/CT scan is recommended, and the lesion site with the highest abnormal uptake value is selected for re-pathological biopsy to rule out aggressive lymphoma transformation .
In addition, for patients with relapsed advanced FL, it is also necessary to determine whether the patient has specific treatment indications.
For patients with low tumor burden and no treatment indications, you can choose to wait and see.
Rescue induction therapy selection strategy for R/R FL patients For limited-stage R/R FL patients, low-dose involved field radiotherapy (ISRT) can be selected.
For patients with systemic R/R FL, the choice of rescue induction therapy depends on the previous treatment plan, the efficacy of the previous treatment, the duration of the previous treatment response, and the time to relapse.
If the patient has an early relapse (<12-24 months), non-cross-resistance re-induction chemotherapy is the first choice, such as CHOP (cyclophosphamide, vincristine, doxorubicin, prednisone) followed by bendammus Ting’s chemotherapy regimen, and vice versa.
Other chemotherapy regimens including fludarabine, platinum-based or alkylating agents are also available.
Should patients with R/R FL use rituximab? If the patient's previous rituximab-containing regimen achieves a duration of remission> 6-12 months, rituximab should be added to the rescue induction therapy.
For patients with R/R FL whose previous treatment is clearly refractory to rituximab or who have previously used rituximab-containing regimens, the duration of remission is less than 6 months, the new anti-CD20 monoclonal antibody Otto can be used Rizumab combined with bendamustine (subsequent maintenance therapy with otuzumab), compared with bendamustine monotherapy, the combination of the two can improve patient progression-free survival (PFS) and overall survival (OS) [1].
The results of clinical studies have shown that in patients with relapsed FL, lenalidomide combined with rituximab (R2) regimen has a significant benefit in terms of patient efficiency and PFS compared with rituximab monotherapy.
OS also has an improvement trend [2].
Therefore, for R/R FL, especially for patients who only get short-term remission after first-line chemotherapy, R2 can be chosen as a rescue induction therapy.
For elderly R/R FL patients with comorbidities who are not suitable for chemotherapy, radioimmunotherapy can be selected.
For R/R FL patients with late recurrence (>24 months), the original induction treatment plan can be adopted, and a more moderate treatment plan can also be adopted, such as the R2 plan.
For patients with high tumor burden and elevated lactate dehydrogenase levels, non-cross-resistance second-line induction therapy can be used, such as bendamustine combined with rituximab.
The results of a phase II clinical study evaluating the phosphoinositide 3-kinase (PI3K) inhibitor idelalisib in the treatment of R/R FL patients confirmed the effective clinical activity of idelalisib, but suffered from treatment-related side effects such as infection, delayed colitis and lung The effect of toxicity [3].
Therefore, it is strongly recommended to conduct anti-infection prevention and cytomegalovirus monitoring when using idelalisib.
In recent years, new methods including B-cell signaling pathway inhibitors and other targeted drugs have shown activity in phase II studies, but so far, their benefits have not been confirmed in randomized phase III studies.
Targeting CD19 chimeric antigen receptor (CAR) T cell therapy can provide long-term remission in some patients with R/R FL.
However, due to its treatment-related toxicity, this method is still only suitable for patients with aggressive lymphoma transformation.
patient.
Consolidation/maintenance treatment strategy for R/R FL patients According to previous research results [4], high-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (ASCT) can prolong the PFS of R/R FL patients, and there is a trend to prolong OS.
Therefore, for patients with R/R FL suitable for transplantation, ASCT consolidation therapy should be considered after the salvage induction therapy is effective, especially for the short first remission time (<2-3 years) after the previous treatment with rituximab-containing regimen.
Of patients.
In addition, for the above patients after ASCT consolidation therapy, rituximab maintenance therapy can further improve the patient's PFS [5].
For a very small number of special young R/R FL patients, such as early relapse or refractory patients, and patients with high risk of recurrence or relapse after ASCT, allogeneic hematopoietic stem cell transplantation (Allo-HSCT) with a reduced-dose pretreatment regimen can be considered ) It is expected that the patient will be cured.
A systematic meta-analysis showed [6] that even in R/R FL patients who were rescued induction therapy with a monoclonal antibody-containing regimen, rituximab was subsequently given as maintenance therapy every 3 months (for 2 years) , The patient still has good tolerance, and can significantly prolong the patient’s PFS and OS.
However, for those patients who have received monoclonal antibody maintenance therapy in the first-line treatment, whether the monoclonal antibody maintenance therapy can still be used in the second-line treatment is currently lacking relevant research data, and it is not recommended for the time being.
References: 1.
Cheson BD, Chua N, Mayer J, et al.
Overall survival benefit in patients with rituximab-refractory indolent non-hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN study.
J Clin Oncol.
2018 ;36(22):2259-2266.
2.
Leonard JP, Trneny M, Izutsu K, et al.
AUGMENT: a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma.
J Clin Oncol.
2019 ;37(14):1188-1199.
3.
Gopal AK, Kahl BS, de Vos S, et al.
PI3Kd inhibition by idelalisib in patients with relapsed indolent lymphoma.
N Engl J Med.
2014;370:1008-1018.
4 .
Casulo C, Byrtek M, Dawson KL, et al.
Early relapse of follicular lymphoma after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone defines patients at high risk for death:an analysis from the national LymphoCare study.
J Clin Oncol.
2015;33:2516-2522.
5.
Pettengell R, Schmitz N, Gisselbrecht C, et al.
Rituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma: a prospective randomized trial from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.
J Clin Oncol.
2013;31:1624-1630.
6.
Vidal L, Gafter-Gvili A, Salles G, et al.
Rituximab maintenance for the treatment of patients with follicular lymphoma: an updated systematic review and meta-analysis of randomized trials.
J Natl Cancer Inst.
2011;103:1799-1806.
Stamp "Read the original text", we make progress togetherRituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma: a prospective randomized trial from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.
J Clin Oncol.
2013;31:1624-1630.
6.
Vidal L, Gafter-Gvili A, Salles G, et al.
Rituximab maintenance for the treatment of patients with follicular lymphoma: an updated systematic review and meta-analysis of randomized trials.
J Natl Cancer Inst.
2011;103:1799-1806.
Stamp "Read the original", we make progress togetherRituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma: a prospective randomized trial from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.
J Clin Oncol.
2013;31:1624-1630.
6.
Vidal L, Gafter-Gvili A, Salles G, et al.
Rituximab maintenance for the treatment of patients with follicular lymphoma: an updated systematic review and meta-analysis of randomized trials.
J Natl Cancer Inst.
2011;103:1799-1806.
Stamp "Read the original", we make progress togetherRituximab maintenance for the treatment of patients with follicular lymphoma: an updated systematic review and meta-analysis of randomized trials.
J Natl Cancer Inst.
2011;103:1799-1806.
Stamp "Read the original text", we make progress togetherRituximab maintenance for the treatment of patients with follicular lymphoma: an updated systematic review and meta-analysis of randomized trials.
J Natl Cancer Inst.
2011;103:1799-1806.
Stamp "Read the original text", we make progress together
