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The New England Journal of Medicine Jan 2002The standard treatment for patients with diffuse large-B-cell lymphoma is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Rituximab, a chimeric... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
The standard treatment for patients with diffuse large-B-cell lymphoma is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Rituximab, a chimeric monoclonal antibody against the CD20 B-cell antigen, has therapeutic activity in diffuse large-B-cell lymphoma. We conducted a randomized trial to compare CHOP chemotherapy plus rituximab with CHOP alone in elderly patients with diffuse large-B-cell lymphoma.
METHODS
Previously untreated patients with diffuse large-B-cell lymphoma, 60 to 80 years old, were randomly assigned to receive either eight cycles of CHOP every three weeks (197 patients) or eight cycles of CHOP plus rituximab given on day 1 of each cycle (202 patients).
RESULTS
The rate of complete response was significantly higher in the group that received CHOP plus rituximab than in the group that received CHOP alone (76 percent vs. 63 percent, P=0.005). With a median follow-up of two years, event-free and overall survival times were significantly higher in the CHOP-plus-rituximab group (P<0.001 and P=0.007, respectively). The addition of rituximab to standard CHOP chemotherapy significantly reduced the risk of treatment failure and death (risk ratios, 0.58 [95 percent confidence interval, 0.44 to 0.77] and 0.64 [0.45 to 0.89], respectively). Clinically relevant toxicity was not significantly greater with CHOP plus rituximab.
CONCLUSIONS
The addition of rituximab to the CHOP regimen increases the complete-response rate and prolongs event-free and overall survival in elderly patients with diffuse large-B-cell lymphoma, without a clinically significant increase in toxicity.
Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Female; Humans; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Prednisone; Recurrence; Rituximab; Survival Analysis; Vincristine
PubMed: 11807147
DOI: 10.1056/NEJMoa011795 -
Cancer Management and Research 2023Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin's lymphoma (NHL). 30 ~ 40% of DLBCL patients were resistant to the standard R-CHOP... (Review)
Review
Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin's lymphoma (NHL). 30 ~ 40% of DLBCL patients were resistant to the standard R-CHOP regimen or recurrence after remission. It is currently believed that drug resistance is the main cause of the recurrence and refractory of DLBCL (R/R DLBCL). With the increased understanding of DLBCL biology, tumor microenvironment and epigenetics, some new therapies and drugs like molecular and signal pathway target therapy, chimeric antigen receptor (CAR) T-cell therapy, immune checkpoint inhibitors, antibody drug-conjugate and tafasitamab have been used for R/R DLBCL. This article will review the drug resistance mechanism and novel targeted drugs and therapies of DLBCL.
PubMed: 36873252
DOI: 10.2147/CMAR.S400013 -
OncoTargets and Therapy 2022Diffuse large B-cell lymphoma (DLBCL) represents a curable disease with a 60-70% chance of cure with current R-CHOP chemoimmunotherapy. However, 30-40% of patients are... (Review)
Review
Diffuse large B-cell lymphoma (DLBCL) represents a curable disease with a 60-70% chance of cure with current R-CHOP chemoimmunotherapy. However, 30-40% of patients are refractory or relapsing. Many attempts failed to improve the outcome of DLBCL patients, including the intensification of R-CHOP regimen, consolidation, or maintenance therapy since the introduction of R-CHOP in 2000. Better understanding of both molecular biology of lymphoma cells and the tumor microenvironment raised the hope for future improvement of DLBCL patients' survival. Novel molecular findings have initiated clinical trials exploring targeted therapy based on driver genetic alterations with an intent to improve survival of high-risk subsets of patients. But the preliminary results remain ambiguous. The approach "agnostic" to specific molecular alterations of lymphoma cell includes antibody-drug conjugates (especially polatuzumab vedotin), immunotherapy comprising different antibodies with immunomodulatory effect (tafasitamab, lenalidomide), and T-cell engaging therapy (bispecific antibodies, early use of CAR T-cell). This approach could increase the cure rates and change the current therapeutic paradigm. However, better prognostic stratification, smarter designs of clinical trials, modification of endpoints including the use of ctDNA are needed. This review covers the complexity of DLBCL management.
PubMed: 36510607
DOI: 10.2147/OTT.S326632 -
Faculty Reviews 2023ALK-positive anaplastic large cell lymphoma (ALCL) represents approximately 6-7% of the mature T-cell lymphomas. This subtype contains a translocation between the ALK... (Review)
Review
ALK-positive anaplastic large cell lymphoma (ALCL) represents approximately 6-7% of the mature T-cell lymphomas. This subtype contains a translocation between the ALK gene on chromosome 2 and one of several other genes that together form an oncogene. The most frequent translocation is t(2;5) which combines ALK with NPM1. This lymphoma has a median age of 34 years, is more common in males, and is in advanced stage at the time of diagnosis in most patients. ALK-positive ALCL is the most curable of the peripheral T-cell lymphomas. The CHOP regimen has been most frequently used, but results are improved with the substitution of brentuximab vedotin for vincristine (BV-CHP) and the addition of etoposide (CHOEP), with BV-CHP being favored. Salvage therapies include allogeneic or autologous bone marrow transplantation, BV, if not used as part of the primary therapy, and ALK inhibitors. The latter are very active and likely to be incorporated into the primary therapy.
PubMed: 37655119
DOI: 10.12703/r/12-21 -
Mediterranean Journal of Hematology and... 2023Large B-cell lymphomas (LBCLs) are among the most frequent (about 30%) non-Hodgkin's lymphoma. Despite the aggressive behavior of these lymphomas, more than 60% of... (Review)
Review
Large B-cell lymphomas (LBCLs) are among the most frequent (about 30%) non-Hodgkin's lymphoma. Despite the aggressive behavior of these lymphomas, more than 60% of patients can be cured with first-line chemoimmunotherapy using the R-CHOP regimen. Patients with refractory or relapsing disease show a poor outcome even when treated with second-line therapies. CD19-targeted chimeric antigen receptor (CAR) T-cells are emerging as an efficacious second-line treatment strategy for patients with LBCL. Three CD19-CAR-T-cell products received FDA and EMA approval. CAR-T cell therapy has also been explored for treating high-risk LBCL patients in the first-line setting and for patients with central nervous system involvement. Although CD19-CAR-T therapy has transformed the care of refractory/relapsed LBCL, about 60% of these patients will ultimately progress or relapse following CD19-CAR-T; therefore, it is fundamental to identify predictive criteria of response to CAR-T therapy and to develop salvage therapies for patients relapsing after CD19-CAR-T therapies. Moreover, ongoing clinical trials evaluate bispecific CAR-T cells targeting both CD19 and CD20 or CD19 and CD22 as a tool to improve the therapeutic efficacy and reduce the number of refractory/relapsing patients.
PubMed: 38028399
DOI: 10.4084/MJHID.2023.066 -
Blood Advances Jun 2023The POLARIX trial demonstrated the superiority of polatuzumab vedotin (Pola) over vincristine in the rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone... (Clinical Trial)
Clinical Trial
The POLARIX trial demonstrated the superiority of polatuzumab vedotin (Pola) over vincristine in the rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) regimen for large B-cell lymphomas, but it is unknown whether Pola can be safely incorporated into intensified regimens (eg, dose-adjusted [DA]-EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab]) typically used for the highest risk histologies. This was a single-center, open-label, prospective clinical trial of 6 cycles of Pola-DA-EPCH-R (vincristine omitted) in aggressive large B-cell lymphomas. The primary end point was to estimate the safety of Pola-DA-EPCH-R as measured by the rate of dose-limiting toxicities (DLTs) in the first 2 cycles with prespecified suspension rules. Secondary and exploratory end points included efficacy and correlation with circulating tumor DNA (ctDNA) levels. We enrolled 18 patients on study, and with only 3 DLTs observed, the study met its primary end point for safety. There were 5 serious adverse events, including grade 3 febrile neutropenia (3, 17%), grade 3 colonic perforation in the setting of diverticulitis, and grade 5 sepsis/typhlitis. Among 17 evaluable patients, the best overall response rate was 100%, and the complete response rate was 76%. With a median follow-up of 12.9 months, 12-month event-free survival was 72%, and 12-month overall survival was 94%. No patient with undetectable ctDNA at the end of treatment has relapsed to date. Using Pola to replace vincristine in the DA-EPOCH-R regimen met its primary safety end point. These data support the further evaluation and use of this approach in histologies where the potential benefit of both an intensified regimen and Pola may be desired. This trial was registered at www.clinicaltrials.gov as #NCT04231877.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Etoposide; Lymphoma, Large B-Cell, Diffuse; Prednisone; Prospective Studies; Rituximab; Vincristine
PubMed: 36521030
DOI: 10.1182/bloodadvances.2022009145 -
Cancer Medicine Jul 2023There is no standard first-line immunochemotherapy regimen for transplant-ineligible patients with mantle cell lymphoma (MCL) currently, and the efficacy of various... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is no standard first-line immunochemotherapy regimen for transplant-ineligible patients with mantle cell lymphoma (MCL) currently, and the efficacy of various treatment remains unclear.
METHODS
We conducted a Bayesian network meta-analysis (NMA) of all eligible randomized controlled trials. Pairwise comparisons and ranking of different first-line treatment options were performed.
RESULTS
Nine studies were included in the NMA, involving a total of 2897 MCL patients. The BR-Ibrutinib+R regimen showed the best progression-free survival (PFS), with a surface under the cumulative ranking curve (SUCRA) of 0.89 and probability of being the best treatment (PbBT) of 69%. The VR-CAP regimen was the most potential intervention to improve overall survival (OS), with a SUCRA of 0.89 and PbBT of 63%. Compared with the R-CHOP regimen, the BR regimen achieved a better PFS (hazard ratio [HR] 0.45 [95% credible interval 0.2-0.96]). The BR-Ibrutinib+R regimen (HR 0.14 [0.02-0.99]), BR+R regimen (HR 0.19 [0.034-0.99]), and BR regimen (HR 0.3 [0.08-1.03]) were superior to CHOP regimen with better PFS. The R-FC regimen (HR 2.27 [1.01-5.21]) or FC regimen (HR 3.17 [1.15-8.71]) was inferior to the VR-CAP regimen with a worse OS.
CONCLUSIONS
Our study presents the most promising first-line treatment strategy for transplant-ineligible MCL patients in terms of PFS and OS, which provides innovative treatment strategy for MCL treatment.
Topics: Adult; Humans; Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Bendamustine Hydrochloride; Lymphoma, Mantle-Cell; Network Meta-Analysis; Randomized Controlled Trials as Topic; Rituximab
PubMed: 37264757
DOI: 10.1002/cam4.6183 -
The Oncologist Sep 2018Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of clinically aggressive diseases associated with poor outcome. Despite progress in the last several years,... (Review)
Review
UNLABELLED
Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of clinically aggressive diseases associated with poor outcome. Despite progress in the last several years, resulting in a deeper understanding of the natural history and biology of PTCL based on molecular profiling and next-generation sequencing, there is a need for improvement in efficacy of chemotherapeutic regimens for newly diagnosed patients. Treatment in the front-line setting is most often cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like regimens, which are associated with a high failure rate and frequent relapses. Trials evaluating intensive chemotherapy have resulted in variable success in prolonging event-free survival, but overall survival has remained unchanged. Furthermore, this strategy is limited to patients who are in complete remission after initial anthracycline-based chemotherapy. Many patients are ineligible for hematopoietic stem cell transplantation because of age or failure to achieve remission. For relapsed disease, advances have been made in the therapeutic arsenal for PTCL. New drugs investigated in phase II studies have achieved response rates between 10% and 30%. However, to date the identification of new therapies has been largely empiric, and long-term remissions are the exception to the rule. Current patient outcomes suggest the need for the identification and development of active and biologically rational therapies to improve disease management and to extend the duration of response with iterative biomarker evaluation. This review covers the management of PTCL and focuses on new agents and therapeutic combinations, based on a better understanding of biology and pathogenesis of the disease.
IMPLICATIONS FOR PRACTICE
Recent progress in understanding of the biology and pathogenesis of peripheral T-cell lymphoma has led to the emergence of new drugs. Unfortunately, this has not been met with similar advances in outcome improvement. Anthracycline-containing regimens, mostly cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), are considered the standard of care, although the best first-line approach remains to be defined. In the relapsed and refractory settings, several new agents achieved response rates between 10% and 30%, although these drugs do not significantly affect survival rates. Therapeutic options based on better molecular characterization of various histological types and combinations with the CHOP regimen or synergic combinations of new drugs may lead to better outcomes.
Topics: Humans; Lymphoma, T-Cell, Peripheral
PubMed: 29674443
DOI: 10.1634/theoncologist.2017-0524 -
Journal of Research in Medical Sciences... May 2012Extranodal lymphoma may arise anywhere outside lymph nodes mostly in the gastrointestinal (GI) tract as non-Hodgkin's disease. We reviewed the clinicopathological...
BACKGROUND
Extranodal lymphoma may arise anywhere outside lymph nodes mostly in the gastrointestinal (GI) tract as non-Hodgkin's disease. We reviewed the clinicopathological features and treatment results of patients with primary GI lymphoma.
MATERIALS AND METHODS
A total number of 30 cases with primary GI lymphoma were included in this study. Patients referred to the Radiation Oncology Department of Omid Hospital (Mashhad, Iran) during a 5-year period (2006-11). Clinical, paraclinical, and radiological data was collected from medical records of the patients.
RESULTS
Out of the 30 patients with primary GI lymphoma in the study, 12 were female (40%) and 18 were male (60%) (male to female ratio: 3/2). B symptoms were present in 27 patients (90%). Antidiuretic hormone (LDH) levels were elevated in 9 patients (32.1%). The most common primary site was stomach in 14 cases (46.7%). Other common sites included small intestine and colon each in 8 patients (26.7%). All patients had histopathologically proven non-Hodgkin's lymphoma. The most common histologic subtype was diffuse large B-cell lymphoma (DLBL) in 16 patients (53.3%). In addition, 28 patients (93.3%) received chemotherapy with cyclophosphamide, vincristine, doxorubicin, prednisolone (CHOP regimen). The median course of chemotherapy was 6 cources. Moreover, 8 patients (26.7%) received radiotherapy with cobalt 60. The median follow-up time was 26 months. The overall 5-year survival rate was 53% and the median survival time was 60 months.
CONCLUSION
Primary GI lymphoma is commonly seen in stomach and small intestine and mostly is DLBCL or mucosa-associated lymphoid tissue (MALT) lymphoma.
PubMed: 23626617
DOI: No ID Found -
Ocular Oncology and Pathology Feb 2022The aim of the study was to describe the clinical presentation, management strategies, and outcomes in a case series of primary lacrimal sac tumors.
OBJECTIVE
The aim of the study was to describe the clinical presentation, management strategies, and outcomes in a case series of primary lacrimal sac tumors.
METHODS
This retrospective study was conducted in Sheikh Fajilatunnessa Mujib Eye Hospital and Training Institute, Bangladesh, from July 1 to December 31, 2020, and included all patients who were evaluated, treated, and followed up for at least 6 months from January 2013 to October 2020. One patient developed a recurrence of the adenocarcinoma of the lacrimal sac after 1 year of primary treatment. Patients' demographic data were analyzed and reviewed from published articles on lacrimal sac tumors. We assessed patients clinically, followed by radiological evaluation. We also analyzed the biopsy technique, treatment modality, and recurrence. An oncologist reviewed all patients to prepare a plan for adjuvant treatment.
RESULTS
Ten patients with lacrimal sac tumors were included in this study. Swelling in the medial canthal region was the most common presenting feature (100%), followed by epiphora (60%) and pain (30%). Open biopsy was preferred over fine-needle aspiration biopsy. Incisional biopsy or complete excisional biopsy was performed for all suspected malignancies. Malignant tumors were found in 7 (70%) cases, and benign tumors in 3 (30%) cases. Non-Hodgkin's lymphoma (NHL) (40%) was the most common malignant lacrimal sac tumor. Mucosa-associated lymphoid tissue lymphoma was 75%, and diffuse large B-cell lymphoma was 25% among the cases of NHL. Patients with epithelial malignancy were treated with external beam radiation therapy, while NHL patients were treated with chemotherapy (CHOP regimen). Recurrence was noted in 1 case (10%) of epithelial malignancy after 1 year of treatment.
CONCLUSION
Successful management of lacrimal sac tumors requires a high index of suspicion, as these are fatal tumors, often misdiagnosed as dacryocystitis. Nonepithelial malignancies are more predominant than epithelial malignancies, and hematolymphoid tumors are most frequent.
PubMed: 35356605
DOI: 10.1159/000520086