Patients with aaIPI 2-3 Diffuse Large B-Cell Lymphoma Achieve 75% Long-Term Survival Following First-Line Rituximab-Supplemented High-Dose Sequential Chemotherapy and Autograft: Final Results of the Prospective Phase II GITIL (Gruppo Italiano Terapie Innovative nei Linfomi) Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1889-1889 ◽  
Author(s):  
Corrado Tarella ◽  
Manuela Zanni ◽  
Massimo Di Nicola ◽  
Caterina Patti ◽  
Claudia Castellino ◽  
...  

Abstract Background The outcome of Diffuse Large B Cell Lymphoma (DLB-CL) has been definitely improved by the addition of the anti-CD20 rituximab to conventional chemotherapy. However, despite the advantages offered by rituximab, results are still disappointing in patients presenting with adverse prognostic factors. For these patients, rituximab-supplemented intensive programs with autograft might represent a suitable option. Thus, a prospective multicenter study has been performed using first-line the Rituximab-supplemented high-dose sequential chemotherapy program delivered with multiple autologous peripheral blood progenitor cell (PBPC) support (R-HDS-maps regimen), in DLB-CL patients with score 2 or 3 according to the age-adjusted International Prognostic Index (aaIPI). Preliminary results have been already reported (ASH 2005; Leukemia2007, 21: 1802). Updated results after a prolonged follow-up are here presented. Methods. R-HDS-maps includes: 3 APO courses; sequential administration of hd-cyclophosphamide (CY), hd-Ara-C, both supplemented with Rituximab, hd-etoposide/Cisplatin, with PBPC harvests following hd-CY and hd-Ara-C; hd-Mitoxantrone/L-Pam + 2 further Rituximab doses; involved-field radiotherapy. PBPC rescue was scheduled following Ara-C, etoposide/Cisplatin and Mitoxantrone/L-Pam. Six GITIL Centers participated in the multicenter study, with patients enrolled between November 1999 and September 2004. Results. Overall, 112 consecutive patients (74 score 2, 38 score 3) entered the study protocol. There were 5 early toxic deaths (3 sepsis, 1 pneumonia, 1 JC-virus leucoencephalopathy) + one late toxic death due to pneumonia, at 10 mos.; two more patients died for secondary myelodysplastic syndrome at 3.4 and 3.6 yrs. As reported in Figures 1–2, at a median follow-up of 59 mos., 86 patients (77%) are alive; 79 (70%) are in continuous CR, with a 5-yr event-free survival (EFS) projections of 69%; no significant differences in OS and EFS between subgroups with Germinal-Center and Activated B-cell phenotype were observed. Conclusions. R-HDS-maps regimen: is feasible in a multicenter setting, with a toxicity similar to that of other dose-intense/high-dose regimens; offers prolonged survival to most patients with aaIPI 2–3 DLB-CL. Its comparative efficacy versus R-CHOP-14 is being tested in an ongoing GITIL phase III study. Figure 1 . Overall Survival of 112 aaIPI DLB-CL Figure 1. . Overall Survival of 112 aaIPI DLB-CL Figure 2. Event-free Survival according to GC and ABC phenotype Figure 2. Event-free Survival according to GC and ABC phenotype

2017 ◽  
Vol 35 (5) ◽  
pp. 544-551 ◽  
Author(s):  
Gustaaf W. van Imhoff ◽  
Andrew McMillan ◽  
Matthew J. Matasar ◽  
John Radford ◽  
Kirit M. Ardeshna ◽  
...  

Purpose We compared the efficacy of ofatumumab (O) versus rituximab (R) in combination with cisplatin, cytarabine, and dexamethasone (DHAP) salvage treatment, followed by autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Patients and Methods Patients with CD20+ DLBCL age ≥ 18 years who had experienced their first relapse or who were refractory to first-line R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)–like treatment were randomly assigned between three cycles of R-DHAP or O-DHAP. Either O 1,000 mg or R 375 mg/m2 was administered for a total of four infusions (days 1 and 8 of cycle 1; day 1 of cycles 2 and 3 of DHAP). Patients who experienced a response after two cycles of treatment received the third cycle, followed by high-dose therapy and ASCT. Primary end point was progression-free survival (PFS), with failure to achieve a response after cycle 2 included as an event. Results Between March 2010 and December 2013, 447 patients were randomly assigned. Median age was 57 years (range, 18 to 83 years); 17% were age ≥ 65 years; 63% had stage III and IV disease; 71% did not achieve complete response (CR) or experience response for < 1 year on first-line R-CHOP. Response rate for O-DHAP was 38% (CR, 15%) versus 42% (CR, 22%) for R-DHAP. ASCT on protocol was completed by 74 patients (33%) in the O arm and 83 patients (37%) in the R arm. PFS, event-free survival, and overall survival were not significantly different between O-DHAP versus R-DHAP: PFS at 2 years was 24% versus 26% (hazard ratio [HR], 1.12; 95% CI, 0.89 to 1.42; P = .33); event-free survival at 2 years was 16% versus 18% (HR, 1.10; P = .35); and overall survival at 2 years was 41% versus 38% (HR, 0.90; P = .38). Positron emission tomography negativity before ASCT was highly predictive for superior outcome. Conclusion No difference in efficacy was found between O-DHAP and R-DHAP as salvage treatment of relapsed or refractory DLBCL.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4878-4878
Author(s):  
Heidi Mocikova ◽  
Jozef Michalka ◽  
Jan Koren ◽  
Pavla Stepankova ◽  
Alexander Wild ◽  
...  

Abstract Abstract 4878 Background. Strong CD20 expression in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) suggests the feasibility of rituximab in the treatment of this disease. Methods. We analysed the outcome of 102 patients with NLPHL treated with or without rituximab in combination with conventional treatment: chemotherapy and/or radiotherapy. Histologies were reviewed for the purpose of this study. Rituximab was administered in 26 of 102 NLPHL patients (13 in the first line treatment and in 13 of 20 relapsed patients). Additionally, rituximab with chemotherapy was administered in 11 patients with histologic transformation to diffuse large-B cell lymphoma. Median follow-up was 7.1 years. Median patient age was 34.2 years. Results. The 10-year overall survival (OS) rate and progression - free survival (PFS) of the whole group was 88% and 65%, respectively. There was no difference in OS and PFS in patients with clinical stage IA without risk factors treated without or with rituximab (30 vs 3 patients) and conventional treatment, however the follow-up in the rituximab group was short. The addition of rituximab to conventional treatment did not affect the OS in the group of patients with more advanced disease: 58 patients without vs 10 with rituximab (94% [95% CI: 88 – 100%] vs 100% [-], P=0.566). PFS in both groups did not differ significantly in the first line treatment (69% [95% CI: 57 – 82%] vs 100% [-], P=0.165), however when all lines of treatment were analysed, PFS was significantly better in patients treated without rituximab (92% [95% CI: 84 – 100%] vs 38% [95% CI: 22 – 65%], P< 0.001). Histologic transformation to diffuse large B - cell lymphoma was diagnosed in 11 rituximab naive patients, but this was not statistically significant when compared to 0 patients after rituximab treatment (14,5% vs 0%, P=0.061). Histologic transformation was the only poor prognostic factor that influenced OS (HR 7.936, P=0.004). Conclusions. Rituximab does not prevent relapses in NLPHL. This study confirms favorable OS of NLPHL patients regardless whether rituximab was used or not. The absence of histologic transformation in NLPHL patients treated with rituximab deserves further investigation. Disclosures: No relevant conflicts of interest to declare.


2017 ◽  
Vol 89 (1) ◽  
pp. 43-48
Author(s):  
E I Dorokhina ◽  
A U Magomedova ◽  
I V Galtseva ◽  
V N Dvirnyk ◽  
S A Glinkina ◽  
...  

Aim. To estimate the number of early progenitors of bone marrow (BM) hematopoiesis in patients with diffuse large B-cell lymphoma (DLBCL) in the late period after high-dose chemotherapy (HDCT) according to the mNHL-BFM-90 program. Subjects and methods. The investigators analyzed the results of BM immunophenotypic and histological studies in 40 patients (median age, 57 years) with DLBCL who received HDCT according to the mNHL-BFM-90 program at the Hematology Research Center (HRC), Ministry of Health of the Russian Federation (MHRF), in the period 2002 to 2009. A comparison group consisted of 19 patients (median age, 70 years) treated according to the CHOP/R-CHOP program at HRC, MHRF, in the same period. The median follow-up period was 6 years. The results of BM examination were analyzed before and 5—10 years after the end of HDCT. Immunophenotypic study determined the number of early CD34+ hematopoietic progenitors. BM cellularity, the size of erythroid, granulocytic and megakaryocytic lineages, their ratio, the presence of dysplasia signs, and secondary stromal changes were histologically determined. The BM toxic injury signs found for the first time were evaluated as manifestations of late myelotoxicity. Results. At 5-to-10-year follow-ups after the end of HDCT according to the mNHL-BFM-90 program, the patients showed a smaller number of early CD34+ progenitors of BM hematopoiesis in 31 (78%) cases than those treated according to the CHOP/R-CHOP-21 program (n=8 (2%)) (p=0.005). Myelopoiesis with decreased CD34+ cell count was characterized by hypocellularity in 8 (26%) patients (p=0.07), the narrowing of megakaryocytic lineage in 14 (45%) (p=0.006), erythroid one in 7 (23%) (p=0.01), and granulocytic one in 8 (26%) (p=0.92), pronounced secondary stromal changes in 15 (48%) (p=0.03), and grade 1 thrombocytopenia in 13 (42%); p=0.02). Conclusion. There is evidence that the number of early CD34+ progenitors of BM hematopoiesis decreased in patients with DLBCL in the late period after HDCT. The investigation shows the relationship of the reduction in the number of early CD34+ progenitors of BM hematopoiesis in the late follow-up period to the presence of pronounced secondary changes in the BM stroma (p=0.02). There was no statistically significant relationship of the decreased number of CD34+ cells to the age younger or older than 60 years, to the period after the end of chemotherapy, to gender or presence of specific BM injury.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4440-4440
Author(s):  
Beatrice Casadei ◽  
Alessandro Broccoli ◽  
Vittorio Stefoni ◽  
Cinzia Pellegrini ◽  
Letizia Gandolfi ◽  
...  

Abstract The first line treatment for primary mediastinal large B-cell lymphoma (PMLBCL) still remains a matter of debate even if the literature confirms that an anthracycline-containing regimen should be the main choice. The European experience shows the superiority of “third-generation” dose-dense regimen like MACOP-B (methotrexate, doxurubicin, cyclophosphamide, vincristine, bleomycin, prednisone) or VACOP-B (same as MACOP-B, with etoposide instead of methotrexate) over CHOP (cyclophosphamide, adriamycin, vincristine and prednisone) or CHOP-like regimen. The addition of rituximab to third-generation regimen does not seem to cause any advantages in terms of overall survival (OS) and progression free-survival (PFS), while external radiotherapy (RT) has shown a good efficacy as a consolidation strategy at the end of induction chemotherapy, especially in converting partial responses (PR) into complete responses (CR). Between October 1989 and April 2010, 98 (58 females and 40 males) previously untreated PMLBCL patients were diagnosed and subsequently treated at our Institution. All patients were treated with MACOP-B regimen, concurrent rituximab was administered in 57 patients (58.2%) and 67 patients (68.4%) received mediastinal RT. Among 57 patients who received rituximab, 37 (64.9%) underwent RT whereas, among 41 who did not receive rituximab, RT was delivered in 30 (group 4, 73.2%) patients. 11 patients (group 1, 11.2%) received chemotherapy alone and 37 (group 3, 37.8%) received besides immunotherapy and RT (Table 1). All patients were assessed at the diagnosis and after the treatment with computed tomography and positron emission tomography (after 2001) scan. Main aims of our study were the effectiveness of the regimen measured as overall response rate (ORR) and patients survival. Sixty-one (62.2%) out of 98 patients achieved a CR and 27 (27.6%) were in PR after 12 cycles of MACOP-B regimen (with or without rituximab). Twenty-one patients in PR after (immuno)chemotherapy converted the response into CR with mediastinal RT. At the end of the scheduled treatment, 82 patients (83.7%) achieved a CR and 6 a PR (6.1%), yielding an ORR of 89.8%. At a median follow-up of 5.6 years, 9 patients relapsed within the first 2 years of treatment. During the follow-up 15 patients died, of whom 13 as a consequence of disease relapse or progression. The projected OS at 17 years is 72% with a PFS and a disease free survival (DSF) of 86.8% and 88.4% respectively (Figure 1 A-C). The subgroup analysis shows a statistically significant difference in term of OS (p=0.0003) but not in term of PSF and DFS among the four groups of treatment (Figure 1 D-F). All the patients receiving consolidation RT obtained a CR without differences between subgroup 3 and 4. RT seems to have a small consolidative potential in patients who obtained CR after chemo-immunotherapy alone: there are no differences in term of DFS between subgroup 2 and 3. No statistically significant differences in terms of OS, PFS and DSF occurred among patients received rituximab or not, regardless of a subsequent RT. Our monocentric experience spans a period of 20 years and indicates that a third-generation regimen like MACOP-B is feasible and could be a standard of first line treatment for PMLBCL. In agreement with the literature, adding rituximab doesn’t improve the outcome. Mediastinal RT, delivered as a consolidative strategy, impacts on global survival and on CR rates. In particular, RT after third-generation regimen remains a good strategy to convert PR into CR, but it may be avoided in patients obtaining CR after (immuno)chemotherapy. Table 1 Group MACOP-B Rituximab Radiotherapy N (%) 1 Yes No No 11 (11.2%) 2 Yes Yes No 20 (20.4%) 3 Yes Yes Yes 37 (37.8%) 4 Yes No Yes 30 (30.6%) TOTAL N (%) 98 (100%) 57 (58.2%) 67 (68.4%) 98 (100%) Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Vol 4 (14) ◽  
pp. 3382-3390
Author(s):  
David Sermer ◽  
Sabela Bobillo ◽  
Ahmet Dogan ◽  
Yanming Zhang ◽  
Venkatraman Seshan ◽  
...  

Abstract High-grade B-cell lymphoma (HGBL) with translocations involving MYC and BCL2 or BCL6 comprises ∼10% of cases of diffuse large B-cell lymphoma (DLBCL) and carries a poor prognosis. The incidence, prognosis, and optimal therapy for DLBCL harboring extra copies of the genes MYC, BCL2, and BCL6, rather than their genetic translocations, are unknown. In this retrospective, single-center study we identified 144 DLBCL cases including 46 patients with classic HGBL with double-hit or triple-hit chromosomal translocations (DHL), 55 with extra copies of MYC in addition to aberrations (extra copies or translocations) of BCL2 and/or BCL6 but did not meet the criteria for HGBL (EC group), and 43 without any aberrations of MYC, BCL2, or BCL6 (wild type [WT]). Unfavorable baseline characteristics had similar frequency in the EC and WT groups, but were significantly more prevalent in the DHL group. With a median follow-up of 36 months, the 2-year event-free survival (EFS) was similar between the WT and EC groups at 77% (95% confidence interval [CI], 65-90) and 82% (95% CI, 72-93), respectively. In contrast, the 2-year EFS of the DHL group was 63% (95% CI, 51-79). The 2-year overall survival in the WT, EC, and DHL groups was 86% (95% CI, 76-97), 89% (95% CI, 81-98), and 74% (95% CI, 62-88), respectively. Among patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), the EC group had outcomes similar to those of the WT group. Our results indicate that patients with DLBCL with extra gene copies of MYC, BCL2, and BCL6 fare differently from those with HGBL and respond well to standard R-CHOP therapy.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17556-17556
Author(s):  
C. L. Mello ◽  
O. Feher ◽  
V. C. Lima ◽  
C. Valadares ◽  
F. A. Soares ◽  
...  

17556 Objectives: Primary mediastinal B-cell Lymphoma (PMBL) is recognized as a separate entity in the WHO classification. Treatment for PMBL is based on a combination of conventional dose chemotherapy, high dose chemotherapy and radiation therapy. The best strategy is still undefined. We conducted a retrospective analysis of patients with PBML to identify clinical prognostic factors. Methods: A retrospective analysis of 43 patients treated at Hospital do Cancer AC Camargo, Sao Paulo, Brazil, between 1989 and 2004. All patients had previous diagnosis of diffuse large B-cell lymphoma, with positive CD20 on neoplastic cells. A predominant anterior mediastinal lesion should be present. Induction chemotherapy regimens were grouped in first generation (CHOP/CHOP-like), third generation (PromaceCytabon/MACOP) and other (pediatric regimens, COP). Results: Age ranged from 16 to 82 years-old, 30 females and 13 male. Age < 35 yo was associated with a better prognosis (5 years OS - 56% × 34%, p = 0.048). Among clinical variables, female gender, stage IA-IIB, IPI 0–1, normal LDH, absence of mediastinal bulky disease were associated with better prognosis, although not statistically significant. Response rate to first generation regimens was: 37% CR (11/29), 24% PR (7/29) and 24% PD (7/29). Four patients were treated with Third generation regimens with 2 CR and 2 PR. 20 out of 25 patients with PR or CR to first line chemotherapy received mediastinal radiation therapy. More than 65% of patients had a follow up of 5 years or more. With a median follow up of 22.3 months, projected 5 year OS was 47% and for the responders the median PFS was 8,4 months. No difference in OS and PFS was observed among the three chemotherapy groups. Conclusion: Our analysis showed that response rate to first line regimens was around 60% and 25% of patients were primarily refractory to CHOP regimen. Age younger than 35 years old was associated with a better prognosis. 5 years overall survival was 45% and is in accordance with the literature. Although recent studies have demonstrated biological similarities between PMBL and Hodgkin’s Lymphoma, the prognosis of PMBL is less favorable than HL. Better understanding of the disease will help in developing more appropriate therapeutic strategies for PMBL. No significant financial relationships to disclose.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18536-18536 ◽  
Author(s):  
I. Poddubnaya ◽  
E. Osmanov ◽  
L. Babicheva ◽  
G. Tumyan ◽  
E. Sorokin ◽  
...  

18536 Background: R-CHOP is regarded as the best available treatment for untreated patients with aggressive and indolent B- NHL. Methods: 184 previously untreated patients with DLCL were included in retrospective study: 92 patients were treated by CHOP, 92 patients were treated by CHOP plus rituximab ( R-CHOP ). Age of patients ranged 16–87 years (median 50 years). The median follow- up was 18 months. Compared groups were balanced in all parameters. The advanced stage of disease (III-IV) at diagnosis had 66% patients treated with CHOP and 67,5 % patients treated with R-CHOP. =2 extranodal zones were initially revealed at 35% in CHOP group vs 47% in R- CHOP group. PS of 25 % patients in R-CHOP group and 30% patients in CHOP group was regarded as appropriate 3–4 degrees on ECOG. Increased LDH level was marked at 60% in CHOP-group vs 54% in R-CHOP. 29% patients in R-CHOP group and 21% patients in CHOP group had B-symptoms at diagnosis; bulky disease took place in 53% cases in R-CHOP group and 62% cases in CHOP. High IPI score had 47 % patients in CHOP-group vs 48 % in R-CHOP. Results: Complete response was achieved in 74% of the patients treated with R- CHOP, as compared to 56% of those treated with CHOP alone (p<0,05). Disease progression during treatment was reported in 25% of patients in CHOP group and 18,5% in R-CHOP group. Median overall survival in patients treated with R-CHOP was NS, in patients treated with CHOP alone was 16 months. With a median follow-up of 18 months, 29 (31,5%) events (progression - 18,5%, relapse - 10%, death - 3% ) were observed in the R-CHOP group and 48 (52%) events ( progression - 25%, relapse - 20%, death - 7%) in the CHOP group (p<0,05). Median event-free survival and relapse-free survival in the CHOP group was 12 months, in R-CHOP group NS. Toxicity was equivalent in both groups. Conclusions: We have established better direct efficiency and outcome of R-CHOP in any age of pts. No significant financial relationships to disclose.


2012 ◽  
Vol 87 (9) ◽  
pp. 880-885 ◽  
Author(s):  
Bridget Charbonneau ◽  
Matthew J. Maurer ◽  
Zachary S. Fredericksen ◽  
Clive S. Zent ◽  
Brian K. Link ◽  
...  

2005 ◽  
Vol 23 (18) ◽  
pp. 4117-4126 ◽  
Author(s):  
P. Feugier ◽  
A. Van Hoof ◽  
C. Sebban ◽  
P. Solal-Celigny ◽  
R. Bouabdallah ◽  
...  

Purpose To analyze the long-term outcome of patients included in the Lymphome Non Hodgkinien study 98-5 (LNH98-5) comparing cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) to rituximab plus CHOP (R-CHOP) in elderly patients with diffuse large B-cell lymphoma. Patients and Methods LNH98-5 was a randomized study that included 399 previously untreated patients, age 60 to 80 years, with diffuse large B-cell lymphoma. Patients received eight cycles of classical CHOP (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, and prednisone 40 mg/m2 for 5 days) every 3 weeks. In R-CHOP, rituximab 375 mg/m2 was administered the same day as CHOP. Survivals were analyzed using the intent-to-treat principle. Results Median follow-up is 5 years at present. Event-free survival, progression-free survival, disease-free survival, and overall survival remain statistically significant in favor of the combination of R-CHOP (P = .00002, P < .00001, P < .00031, and P < .0073, respectively, in the log-rank test). Patients with low-risk or high-risk lymphoma according to the age-adjusted International Prognostic Index have longer survivals if treated with the combination. No long-term toxicity appeared to be associated with the R-CHOP combination. Conclusion Using the combination of R-CHOP leads to significant improvement of the outcome of elderly patients with diffuse large B-cell lymphoma, with significant survival benefit maintained during a 5-year follow-up. This combination should become the standard for treating these patients.


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