Relationship between response rates and median progression-free survival in non-Hodgkin's lymphoma: A meta-analysis of published clinical trials

2017 ◽  
Vol 36 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Naveen Mangal ◽  
Ahmed Hamed Salem ◽  
Mengyao Li ◽  
Rajeev Menon ◽  
Kevin J. Freise
Keyword(s):  
Clinical Trials ◽  
Hodgkin’S Lymphoma ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Response Rates ◽  
Hodgkin's Lymphoma ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Autologous versus allogeneic bone marrow transplantation for non-Hodgkin's lymphoma: a case-controlled analysis of the European Bone Marrow Transplant Group Registry data.

1992 ◽  
Vol 10 (11) ◽  
pp. 1690-1695 ◽  
Author(s):  
R Chopra ◽  
A H Goldstone ◽  
R Pearce ◽  
T Philip ◽  
F Petersen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Hodgkin’S Lymphoma ◽  
Progression Free Survival ◽  
Lymphoblastic Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Controlled Study ◽  
Progression Rate ◽  
Free Survival ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

PURPOSE A case-controlled study of patients who reported to the European Bone Marrow Transplant Group (EBMTG) was performed to investigate the relative roles and efficacy of allogeneic (alloBMT) and autologous bone marrow transplantation (ABMT) in non-Hodgkin's lymphoma. PATIENTS AND METHODS Of 1,060 patients who reported to the lymphoma registry, 938 patients underwent ABMT and 122 patients underwent alloBMT. A case-controlled study was performed by matching 101 alloBMT patients with 101 ABMT patients. The case matching was performed after the selection of the main prognostic factors for progression-free survival by a multivariate analysis. RESULTS The progression-free survival was similar in both types of transplants (49% alloBMT v 46% ABMT). The overall relapse and progression rate for the alloBMT patients was 23% compared with 38% in the ABMT patients. This difference was not significant statistically. In the lymphoblastic lymphoma subgroup, alloBMT was associated with a lower relapse rate than ABMT (24% alloBMT v 48% ABMT; P = .035). The progression-free survival, however, was not significantly different because patients with lymphoblastic lymphoma who underwent alloBMT had a higher procedure-related mortality (24% alloBMT v 10% ABMT; P = .06). A significantly lower relapse/progression rate was also observed in patients with chronic graft-versus-host disease (cGVHD) compared with those patients without (0% cGVHD v 35% no cGVHD; P = .02). Fourteen of 18 patients who had cGVHD also had lymphoblastic lymphoma. CONCLUSION This study suggests that ABMT and alloBMT for non-Hodgkin's lymphoma are comparable, with the exception of lymphoblastic lymphoma in which a graft-versus-lymphoma effect may account for the lower relapse rate for patients who underwent alloBMT.

Rationale for Consolidation to Improve Progression‐Free Survival in Patients with Non‐Hodgkin's Lymphoma: A Review of the Evidence

2009 ◽  
Vol 14 (S2) ◽  
pp. 17-29 ◽  
Author(s):  
Franck Morschhauser ◽  
Martin Dreyling ◽  
Ama Rohatiner ◽  
Fredrick Hagemeister ◽  
Angelika Bischof Delaloye
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Progression Free Survival ◽  
Hodgkin's Lymphoma ◽  
Free Survival ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Prognostic Implications of the Differentiation Inhibitory Factornm23-H1 Protein in the Plasma of Aggressive Non-Hodgkin’s Lymphoma

Blood ◽  
1999 ◽  
Vol 94 (10) ◽  
pp. 3541-3550 ◽  
Author(s):  
Nozomi Niitsu ◽  
Junko Okabe-Kado ◽  
Takashi Kasukabe ◽  
Yuri Yamamoto-Yamaguchi ◽  
Masanori Umeda ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Hodgkin’S Lymphoma ◽  
Progression Free Survival ◽  
Hodgkin's Lymphoma ◽  
Enzyme Linked Immunosorbent Assay ◽  
Free Survival ◽  
Non Hodgkin’S Lymphoma ◽  
Response To Chemotherapy ◽  
Non Hodgkin's Lymphoma

The outcome of patients with non-Hodgkin’s lymphoma has been improved by current approaches to treatment. Nevertheless, many patients either do not have a complete remission or ultimately relapse. To identify such patients, it is important to be able to predict the outcome. We previously found that the differentiation inhibitory factor/nm23 was correlated with the prognosis of acute myeloid leukemia. To examine the prognostic effect of nm23 on non-Hodgkin’s lymphoma, we established an enzyme-linked immunosorbent assay procedure to determine nm23-H1 protein levels in plasma and assessed the association of this protein level with the response to chemotherapy, overall survival, and progression-free survival in patients with aggressive non-Hodgkin’s lymphoma. The plasma concentration of nm23-H1 was significantly higher in patients with malignant lymphoma than in normal controls, especially in aggressive non-Hodgkin’s lymphoma. The complete remission rate in patients with higher nm23-H1 levels was significantly worse than that in patients with lower nm23-H1 levels. Overall survival and progression-free survival were also lower in patients with higher nm23-H1 levels than in those with lower levels. The 3-year survival rates in patients with low and high nm23-H1levels were 79.5% and 6.7% (P = .0001). A multivariate analysis of prognostic factors showed that the plasma nm23-H1level was independently associated with the survival and progression-free survival. An elevated plasma nm23-H1concentration predicts a poor outcome of advanced non-Hodgkin’s lymphoma. Therefore, nm23-H1 in plasma may be useful for identifying a distinct group of patients at very high risk.

Interferon Alfa Consolidation After Intensive Chemotherapy Does Not Prolong the Progression-Free Survival of Patients With Low-Grade Non-Hodgkin’s Lymphoma: Results of the Southwest Oncology Group Randomized Phase III Study 8809

2000 ◽  
Vol 18 (10) ◽  
pp. 2010-2016 ◽  
Author(s):  
Richard I. Fisher ◽  
Bruce W. Dana ◽  
Michael LeBlanc ◽  
Carl Kjeldsberg ◽  
Jeffrey D. Forman ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Progression Free Survival ◽  
Interferon Alfa ◽  
Hodgkin's Lymphoma ◽  
Phase Iii ◽  
Low Grade ◽  
Consolidation Therapy ◽  
Free Survival ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

PURPOSE: S8809 is a randomized phase III trial determining whether intensive cytoreductive treatment, followed by interferon consolidation at the time of minimal residual disease, prolongs the progression-free survival (PFS) or overall survival (OS) of indolent lymphoma patients. PATIENTS AND METHODS: Five hundred seventy-one patients with previously untreated stage III or IV low-grade non-Hodgkin’s lymphoma were registered. Patients received six to eight cycles of prednisone, methotrexate, doxorubicin, cyclophosphamide, and etoposide/mechlorethamine, vincristine, procarbazine, and prednisone (ProMACE[day 1]-MOPP[day 8]) chemotherapy or chemotherapy plus radiotherapy. Responding patients were randomized to observation alone or to interferon consolidation. Interferon alfa-2b 2 mU/m2 was given subcutaneously three times weekly for 2 years. RESULTS: Two hundred sixty-eight eligible patients were randomized to interferon alfa consolidation (n = 144) or observation alone (n = 124). With a median follow-up time from randomization among patients still alive of 6.2 years, the median PFS time was 4.1 years for patients who received interferon consolidation therapy and 3.2 years for patients who were observed after ProMACE-MOPP induction (P = .25). The adjusted hazard ratio for relapse for observation to interferon was 0.83 (95% confidence interval [CI], 0.61 to 1.13). The median OS has not been reached in either group. At 5 years, OS is 78% for the interferon group and 77% for the observation group (P = .65). The adjusted hazard ratio for survival for observation to interferon is 1.11 (95% CI, 0.69 to 1.79). CONCLUSION: Interferon alfa consolidation therapy after intensive treatment with anthracycline-containing combination chemotherapy and involved-field radiation therapy does not prolong the PFS or OS of patients with low-grade non-Hodgkin’s lymphoma.

MACOP-B versus ProMACE-MOPP in the treatment of advanced diffuse non-Hodgkin's lymphoma: results of a prospective randomized trial by the non-Hodgkin's Lymphoma Cooperative Study Group.

1994 ◽  
Vol 12 (7) ◽  
pp. 1366-1374 ◽  
Author(s):  
M R Sertoli ◽  
G Santini ◽  
T Chisesi ◽  
A M Congiu ◽  
A Rubagotti ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Progression Free Survival ◽  
Hodgkin's Lymphoma ◽  
Study Group ◽  
High Grade ◽  
Cooperative Study ◽  
Cooperative Study Group ◽  
Free Survival ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

PURPOSE The aim of our study was to compare in a multicentric randomized trial two regimens widely used in the treatment of advanced-stage intermediate- to high-grade non-Hodgkin's lymphoma and to assess whether a third-generation regimen (methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B]) was superior to a second-generation regimen (procarbazine, methotrexate with leucovorin, doxorubicin, cyclophosphamide, and etoposide [ProMACE-MOPP]). PATIENTS AND METHODS Between January 1987 and August 1991, 221 patients with diffuse intermediate- to high-grade non-Hodgkin's lymphoma (Working Formulation groups F, G, H, and K), stage II bulky (> 10 cm), III, or IV, were randomized by the Non-Hodgkin's Lymphoma Cooperative Study Group (NHLCSG) to receive ProMACE-MOPP for six cycles or MACOP-B for 12 weeks. Survival, progression-free survival, and disease-free survival were determined, and multivariate analysis of prognostic factors was performed. RESULTS In the two groups of patients, there was no significant difference in terms of complete remission (CR) rate (49.1% with ProMACE-MOPP and 52.3% with MACOP-B), 3-year overall survival rate (45.2% with PROMACE-MOPP and 52.3% with MACOP-B), and 3-year progression-free survival rate (36.4% with ProMACE-MOPP and 36.1% with MACOP-B). In terms of toxicity, no significantly greater toxicity occurred in either arm. Overall toxicity was acceptable. The most frequent side effects were grade II through IV leukopenia, infection, mucositis, and anemia. Treatment-related deaths were equally distributed. CONCLUSION No significant differences in terms of efficacy and/or toxicity between ProMACE-MOPP and MACOP-B are evident. These results are consistent with recent randomized trials showing that the new-generation aggressive regimens are no better than previous ones.

scholarly journals Thalidomide Combined with Interferons for the Treatment of Recurrent or Refractory Non-Hodgkin's Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5341-5341
Author(s):  
Fangfang Yuan ◽  
Hao Ai ◽  
Qingsong Yin ◽  
Lin Chen ◽  
Ruihua Mi ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Adverse Reactions ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Hodgkin's Lymphoma ◽  
Interferon Α ◽  
Free Survival ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract This study examined the clinical efficacy and safety of thalidomide combined with interferons for the treatment of recurrent/refractory non-Hodgkin's lymphoma. We retrospectively analysed the clinical data of 42 patients with recurrent or refractory non-Hodgkin's lymphoma (NHL) who were treated with a regimen of thalidomide combined and interferon α-1b (IFNα-1b) at Henan Tumour Hospital from July 2007 to January 2017. Specifically, the patients initially received 100 mg thalidomide in tablet form once daily at bedtime. If the patient tolerated the drug, the dose was increased to 200 mg. Recombinant human interferon α-1b was subcutaneously injected at a dosage of 60 μg every other day over a period of four weeks. The efficacy was monitored throughout each treatment cycle, adverse reactions were evaluated, and the progress of the disease was assessed during follow-up visits. Relevant indicators, such as the overall response rate (ORR), the overall survival (OS), the progression-free survival (PFS) for all patients, and the safety of the regimen, were analysed. Forty-two patients were treated with a regimen of thalidomide combined with interferons for at least 1 period. The efficacy of the treatment was evaluated for each patient. The objective response rate (CR + PR) was 73.8%. The median overall survival time was 28 months and the median progression-free survival (PFS) time was 21 months. According to the standards of lymphoid malignancies classified by the WHO in 2001, 36 patients were diagnosed with B-cell lymphoma, 24 of whom suffered from recurrent or refractory mantle cell lymphoma (MCL). The combination of thalidomide and interferons improved the conditions of 16 MCL patients, 8 of whom experienced CR and 8 of whom experienced PR. The median OS was 28 months, and the median PFS was 19 months for the patients with MCL. The primary adverse effects of the regimen were drug-induced fever and joint pain caused by the IFN and neurotoxicity and constipation caused by the thalidomide. The adverse reactions ranged in severity from degree I~II and could be alleviated by symptomatic treatment. Serious adverse reactions, such as anaphylactic shock, deep vein thrombosis and bradycardia, did not occur. Disclosures No relevant conflicts of interest to declare.

Single Agent Metronomic Cyclophosphamide in Refractory,Non-Hodgkin's Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4776-4776
Author(s):  
Caroline Hamm ◽  
Sindu M. Kanjeekal ◽  
John Mathews ◽  
Yasmin Alam ◽  
Sam Yoshida ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Hodgkin’S Lymphoma ◽  
Conflicts Of Interest ◽  
Single Agent ◽  
Progression Free Survival ◽  
Hodgkin's Lymphoma ◽  
Free Survival ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Significant Difference

Abstract Abstract 4776 n this retrospective review, we report a case series of eight patients with refractory, heavily pre-treated non-Hodgkin's lymphoma(NHL), treated with low dose cyclophosphamide. Median number of prior treatment regimens was 3. The median disease free survival was 15.5 months with three patients in ongoing CR at the time of reporting with 15 - 36 months of followup. In a comparative group of 6 patients with other malignancies beside NHL (3 chronic lymphocytic leukemia, 2 breast cancer, 1 thymoma, and one small cell carcinoma) the median progression free survival was significantly worse at 3 months. Interestingly the thymoma had a progression free survival of 36 months. Toxicity was minimal. One patient stopped because of thrombocytopenia. One of the patients with ongoing CR at 36 months stopped after 11 months of treatment. One patient died in CR of anal cancer after 15 months of treatment. These results demonstrate an easily tolerable and surprisingly effective treatment option in patients with non-Hodgkin's lymphoma who are not candidates for bone marrow transplantation. The mechanism of action of metronomic chemotherapy has been proposed as anti-angiogenic. We suggest an alternate mechanism of action: that of immunomodulation. We are suggesting this alternate explanation in view of the significant difference in the response rate between those disease that are known to immunogenic and those that may be less so, as well as the well-known immunogenic affect of cyclophosphamide. Further studies are ongoing to investigate this hypothesis. Disclosures: No relevant conflicts of interest to declare.

Efficacy and Safety of Obinutuzumab (GA101) Monotherapy in Relapsed/Refractory Indolent Non-Hodgkin's Lymphoma: Results From a Phase I/II Study (BO20999)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 268-268 ◽  
Author(s):  
Gilles Andre Salles ◽  
Franck Morschhauser ◽  
Catherine Thieblemont ◽  
Philippe Solal-Celigny ◽  
Thierry Lamy ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Hodgkin’S Lymphoma ◽  
Progression Free Survival ◽  
Hodgkin's Lymphoma ◽  
Phase Iii ◽  
Long Term Results ◽  
Free Survival ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract Abstract 268 Obinutuzumab (GA101) is the only type II glycoengineered, humanized anti-CD20 monoclonal antibody in clinical development for the treatment of lymphoma and chronic lymphocytic leukemia. The efficacy of GA101 monotherapy in patients with relapsed/refractory indolent non-Hodgkin's lymphoma (iNHL) is under investigation, and here we report response and long-term results from a Phase I/II study (BO20999). Phase I was a non-randomized dose-escalating study (3 + 3 design; n = 21) with GA101 monotherapy (50–2,000 mg) on Days 1 and 8 of Cycle 1, and Day 1 of Cycles 2–8 (21-day cycles). The primary objective was to determine the safety and pharmacokinetics of GA101 in patients with NHL. In Phase II patients with iNHL were randomized to receive GA101 at one of two doses: 1,600 mg on Days 1 and 8 of Cycle 1 and then 800 mg on Day 1 of Cycles 2–8 (1,600/800 mg; n = 22), or 400 mg on Days 1 and 8 of Cycle 1 and on Day 1 of Cycles 2–8 (400/400 mg; n = 18). The primary efficacy endpoint was end of treatment response, assessed 4 weeks after the last infusion. Secondary endpoints included safety, pharmacokinetics, best overall response (BOR), and progression-free survival (PFS). In indolent patients that entered Phase I (n = 16), response was observed in 9 (56%) patients, with a complete response (CR) in 5 (31%) patients and a partial response (PR) in 4 (25%) patients. No clear dose-response relationship was observed. In Phase II, baseline patient characteristics were similar for each cohort (Table 1) with most patients having follicular lymphoma (FL). In the subpopulation of patients with FL, BOR was observed in 5/14 (35.7%) patients (CR unconfirmed: 1 [7.1%]; PR: 4 [28.6%]) in the 400/400 mg cohort; for the 1,600/800 mg cohort, 12/20 (60%) patients with FL responded (CR: 3 [15%]; CR unconfirmed: 1 [5.0%]; PR: 8 [40%]). After a median observation time of 23.1 months, median PFS for patients with FL was 11.8 months (range: 1.8–22.8 months) for the 1,600/800 mg cohort and 6.0 months (range: 1.0–30.0 months) for the 400/400 mg cohort (HR: 0.77 [95% CI 0.34–1.77) (Figure 1). In the 400/400 mg cohort, 2 patients with FL are in continued responses at 16.9+ and 19.3+ months; 2 others experienced a delayed lasting response (time to response: 13.8 and 12.1 months; duration of response: 7.0 and 10.8 months). Of the 12 responders with FL in the 1,600/800 mg cohort, 3 patients have ongoing response for ≥ 19 months (19.8, 19.9 and 20.4 months). One patient with lymphocytic lymphoma also experienced a response duration of 20.3 months. Efficacy results in the overall population are in line with the FL subpopulation. In patients refractory to rituximab treatment (n = 22), response was observed during the study in 3/12 patients (25%) and in 6/10 patients (60%) in the 400/400 mg cohort and the 1600/800 mg cohort respectively. In Phase II, GA101 was well tolerated in both iNHL cohorts. Infusion-related reactions (IRRs) were the most common adverse event (AE) (400/400 mg: 72%; 1,600/800 mg: 73%). Grade 3/4 AEs occurring in >5% of all patients (both cohorts) included infections and infestations (14%; Herpes zoster, haemophilus, lung infection, one patient each), neutropenia (14%) and IRRs (9%) in the 1,600/800 mg cohort, with none in the 400/400 mg cohort. Re-treatment with GA101 on relapse was permitted as per protocol. To date, 3 patients from Phase II and 2 from Phase I have been re-treated with GA101, with 3 of these 5 patients responding again to GA101.Table 1.Patient baseline characteristics (Phase II)Characteristic400/400 mg (n = 18)1,600/800 mg (n = 22)All (n = 40)Histology, nFollicular142034Other426Clinical stage at diagnosis (Ann Arbor)I–II033III–IV171835Unknown112Median age, years (range)51.0 (42–79)61.5 (44–76)60.5 (42–79)Median number of prior treatments (range)3 (1–8)3 (1–11)3 (1–11)Prior stem cell transplant, n6814Previous rituximab, n172138Rituximab refractory*, n121022*Rituximab refractory: those patients who have had no response or a response of <6 months to a rituximab-containing regimen (rituximab monotherapy or in combination with chemotherapy) at any point during their treatment history.Figure 1Progression-free survival (Phase II, follicular non-Hodgkin's lymphoma)Figure 1. Progression-free survival (Phase II, follicular non-Hodgkin's lymphoma) In conclusion, GA101 monotherapy shows encouraging efficacy with a higher response observed at a higher dose (1,600/800 mg vs 400/400 mg). Phase III trials are ongoing in GA101 in combination with chemotherapy for first-line treatment of patients with advanced iNHL. Disclosures: Salles: Roche: Consultancy, Honoraria. Morschhauser:Roche: Honoraria; Celgene: Consultancy, Honoraria. Wenger:Hoffmann La Roche: Employment. Wassner-Fritsch:Roche: Employment. Asikanius:Roche: Employment. Cartron:Roche: Consultancy, Honoraria; GSK: Honoraria.

Sign in / Sign up

Export Citation Format

Share Document