The Effects of Rituximab Added to Front-Line or Salvage Chemotherapy in Diffuse Large B-Cell Lymphoma (DLBCL) Undergoing High-Dose Chemotherapy (HDC) and Autologous Stem Cell Transplant (ASCT).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1138-1138 ◽  
Author(s):  
Umeer Ashraf ◽  
Ritika Mahajan ◽  
Theresa Hahn ◽  
Shannon L Smiley ◽  
Philip L. McCarthy ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Disease Control ◽  
B Cell ◽  
Salvage Therapy ◽  
Salvage Chemotherapy ◽  
Front Line ◽  
Resistant Disease ◽  
Line Therapy ◽  
Line Setting

Abstract Despite the improved outcome in patients with DLBCL treated with rituximab (R) in combination with systemic chemotherapy (R + chemotherapy), a significant number of patients either relapse or fail to respond as a consequence of resistant disease. HDC and ASCT is the best therapeutic strategy to rescue relapsed/refractory DLBCL. It has been postulated that R+chemotherapy may lead to the selection of highly resistant lymphoma cells diminishing the clinical benefit of HDC and ASCT. Preliminary data from the CORAL study (Gisselbrecht et al Blood2007; 11:517a) suggest that overall response rates (ORR) and 2-year event free survival (EFS) are lower in R+chemotherapy relapsed/ refractory DLBCL when compared to DLBCL treated with chemotherapy alone. However the second randomization of this study to observation versus R-maintenance may affect the interpretation of the data. We retrospectively studied the difference in the outcomes of relapsed/refractory DLBCL patients following HDC and ASCT according to the front line therapy utilized (R+chemotherapy versus chemotherapy). Using the Roswell Park Cancer Institute (RPCI) Tumor Registry and the RPCI Blood and Marrow Transplant (BMT) Database we identified 130 patients with relapsed/refractory NHL who underwent for HDC + ASCT from 1991 to 2008. After excluding patients with a diagnosis other than B-cell DLBCL (patients with transformed NHL were excluded) and those patients receiving allo-BMT after progression from ASCT, the analysis included 63 refractory/ relapsed DLBCL. Demographic characteristics, clinical data, treatment history in the front line and salvage setting were collected. In addition response to salvage therapy and disease status at day +100 from ASCT was recorded for each subject. Progression free and overall survival were calculated from ASCT. Differences in clinical outcomes between patients receiving R as part of first line or salvage treatment and those treated with chemotherapy alone were evaluated by multivariate analysis, adjusting for significant univariate predictors of survival. The patient cohort included 34 males and 29 females with median age of 46 yrs (14.4 to 69.4). Two-thirds of the patients had advance disease and the majority had a Karnofsky performance status (KPS) of 80–100% at diagnosis. R+chemotherapy was given in the front line setting to 25 pts and while 38 received chemotherapy alone. In the salvage setting, 35 pts (55%) received R+chemotherapy. Most relapses (44 pts) occurred within 6 months of completion of front line therapy (17 pts with vs. 27 pts without R). The use of R in the front line setting was associated with significantly higher response rates (PR + CR) to salvage chemotherapy (P = 0.036) and better disease control on day +100 post-ASCT (P = 0.016) when compared to chemotherapy alone. In our cohort, there have been 32 deaths, 23 in chemotherapy treated DLBCL in contrast to 9 deaths in R+chemotherapy treated patients There was a significantly higher response rate post-ASCT for R+chemotherapy treated (as front-line or salvage) DLBCL versus chemotherapy alone (P = 0.007). A multivariate analysis demonstrated that achieving a CR pre-ASCT was the most important predictor of post-ASCT progression free and overall survival . In summary, our data suggest that the use of R + chemotherapy during frontline therapy and in the salvage setting yields better disease control and less incidence of chemo-resistant disease at the time of BMT. Applying the natural selection theory, the use of R+chemotherapy is expected to result in the development of resistant lymphomas. The length of time and the amount of R therapy that will render lymphoma cells resistant to chemo-immunotherapy remain to be determined. Standard doses of R (6 to 8 doses) do not appear to affect response to salvage therapy or autologous BMT outcomes. In our single institution analysis over the last 18 years, it appears that HDC + ASCT is an effective and viable option for patients with R +/− chemotherapy relapsed/refractory DLBCL.

Outcomes of Relapsed/Refractory B-Cell Lymphoma Is Improved by Salvage Chemotherapy Consisting of Two to Three Cycles of Dexamethasone (D), High Dose Ara-C (HA) and Carboplatin (DHAC) with or without Rituximab (R) Followed by Autologous Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5130-5130
Author(s):  
Swaminathan Padmanabhan ◽  
Anjana Elefante ◽  
Prakash Varadarajan ◽  
Minoo Battiwalla ◽  
Arvinder Bir ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
B Cell ◽  
Median Survival ◽  
Salvage Therapy ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Overall Response

Abstract Introduction: Relapsed/refractory B-cell lymphomas are challenging to treat but can be salvaged by High- dose chemotherapy and stem cell transplant (HDC-SCT). Various non-cross resistant salvage regimens have been developed to treat patients with relapsed/refractory B-cell lymphoma. In this report we present our institution’s experience with DHAC ± R in patients requiring salvage therapy prior to HDC-SCT. Methods: The DHAC regimen consists of Dexamethasone at 15mg/m2/dose po every 6 hrs x 10 doses, High-dose Ara-C at 3G/m2 (1.5G/m2 if >50 yrs old) iv over 3 hrs every 12 hrs for 4 doses and Carboplatin at 200mg/m2 iv every 24 hrs for 2 doses. When utilized, patients received rituximab at the standard dose of 375mg/m2, 48 hrs prior to each cycle of DHAC. Growth factor support and anti-microbial prophylaxis was implemented 24 hrs after completion of chemotherapy. The regimen was repeated every 21 days for 2-3 cycles prior to HDC-SCT. We treated 37patients with relapsed/refractory lymphomas; median age was 47 yrs (range 18 – 78); 25 male and 19 females. Histological subtypes included (DLBCL (n=16); follicular lymphoma (n=10); marginal zone lymphoma with blastoid features (n=1); small lymphocytic lymphoma (n=1) and Hodgkin’s lymphoma (n=8). The majority of the patients presented with Stage III (n=43%), Stage IV (n=39%) at the time of DHAC therapy. Seventeen patients were treated with R+DHAC, and 20 were treated with DHAC, either as second line or third line salvage therapy. 19 of 37 proceeded to HD-SCT. Results: The overall response rate (ORR, CR+PR) for all patients was 61% (16 CR and 7 PR). The remaining 14 patients had either stable disease (n=10) or progressed (n=4). Complete responders (43%) had a longer median survival of 107 (range 78 – 136) months compared to 66 months (range 49 – 83) for partial responders (19 percent) and non-responders who had a mean survival of 30.8 months (range 9–54),[P = 0.008]. Patients who proceeded to HD-SCT had an ORR of 79% [11CR and 4 PR] compared to only 44% in those who did not [5 CR and 3 PR]. The median survival in patients transplanted was longer than non-transplanted patients (92 vs 68 months). Conclusions: DHAC with or without rituximab appears to be an effective salvage treatment for patients with relapsed or refractory advanced-stage B-lymphoma undergoing HDC-SCT. An overall response of 61% which increases to 79% when followed by autologous SCT were demonstrated. Median survival was longer in patients experiencing CRs compared to partial or non-responders suggesting that the quality and quantity of the cytoreduction after salvage chemotherapy is an important predictor factor of post-SCT survival. Data looking at prognostic factors predicting response to DHAC±R treatment are being analyzed and will be reported at the ASH annual meeting. Figure 1. Overall survival on DHAC±R depends on response to chemotheraphy. Figure 1. Overall survival on DHAC±R depends on response to chemotheraphy.

Classification of Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) According to the Han's Criteria Defines Two Groups of Patients with Different Clinical Outcomes Following Systemic Rituximab-Multi Agent Anthracycline-Based Therapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 623-623 ◽  
Author(s):  
Julio Chavez ◽  
Mark Walsh ◽  
Francisco J Hernandez-Ilizaliturri ◽  
Anjana Elefante ◽  
Myron S. Czuczman
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Germinal Center ◽  
Predictive Value ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
Front Line ◽  
Free Survival ◽  
Line Therapy

Abstract Abstract 623 Gene expression profiling has successfully distinguished three subtypes of DLBCL with different biology and response to treatment: 1) germinal center B-cell (GCB); and 2) non-germinal center lymphomas, that include: activated B-cell-like (ABC) and Type 3 subtypes. Currently, immunohistochemical (IHC) analysis of lymphoma biopsy specimens appear to be a more widely applicable methodology (i.e. compared to gene microarray analysis) to use in order to differentiate between subtypes of DLBCL. While the clinical benefit of adding rituximab to CHOP or CHOP-like chemotherapy as a front line treatment of DLBCL is beyond dispute, it also requires a re-evaluation of previously accepted biomarkers of response to CHOP or CHOP-like chemotherapy alone. The predictive value of “IHC–defined” GCB phenotype in rituximab-chemotherapy-treated patients continues to be controversial, as retrospective studies have reported conflicting results. In an attempt to define the predictive value of using the Han's algorithm in newly diagnosed DLBCL patients undergoing frontline immunochemotherapy, we retrospectively analyzed differences in progression free survival (PFS) and overall survival (OS) between patients with GCB and non-GCB DLBCL treated with equivalent doses of rituximab and anthracycline-based therapy at our institution. Using the tumor registry and the pharmacy database, we identified patients with DLBCL treated at our Institution between 2000 and 2008. Demographic, clinical, pharmacologic and pathological characteristics were obtained for each patient. Patients were classified into GCB or non-GCB DLBCL according to the Han's algorithm based on the expression of CD10, Bcl-6 and MUM-1 in the large cell component of the tumor specimen. Cumulative doses of rituximab (R), cyclophosphamide (C), doxorubicin (H), vincristine (O), etoposide (E,; when used) and prednisone (P) were calculated for each patient, as well as the number of cycles, dose delays, and growth factor use. A total of 192 patients were included in the study. The average age was 58.65 years (F/M:73/119). Using the Hans algorithm, n=55 (28.6%) and n=57 (29.7%) were classified as non-GCB or GCB, respectively. Inadequate information was availabel to classify 80 patients (undetermined group). Clinical indictors such as clinical demographics, international prognostic index (IPI) score, extra-nodal disease, performance status, Ann Arbor stage, therapy delays, cumulative rituximab and chemotherapy doses were not significantly different between groups (non-GCB, GCB, and undetermined DLBCL). The majority of patients received R+CHOP (90%) or R+ dose adjusted–EPOCH. On follow-up, a total of 42 (21.8%) patients relapsed or were found to have primary-refractory disease. The complete remission rate to front-line therapy was 81% for the entire cohort of patients and was not different between patients with GCB or non-GCB DLBCL. On the other hand, significant differences in PFS and OS were observed between patients with non-GCB versus GCB DLBCL. The 5-year progression free survival (PFS) and overall survival (OS) were significantly better in the GCB DLBCL subtype (75.4% vs. 56.4%, p=0.017 and 84.2% vs. 70.9 %, p=0.037; respectively). As no differences in clinical parameters, CR rate, or rituximab-chemotherapy dose/schedule were observed between non-GCB and GCB DLBCL patients, it is possible that intrinsic biological pathways involved in lymphomagenesis and/or “resistance” of these subtypes of DLBCL may play a role in their responsiveness to rituximab-based immunochemoimmunotherapy. In summary, our data suggest that the Hans algorithm can predict the clinical outcome of patients with DLBCL undergoing front-line therapy with R-chemotherapy. Patients with non-GCB DLBCL while having a comparable initial complete response rate to R+CHOP had a shorter PFS and OS than GCB DLBCL patients. Non-GCB DLBCL represents a subgroup of DLBCL for which innovative therapeutic strategies targeting key regulatory pathways in the induction and/or maintenance setting are needed in an attempt to prolong PFS and improve OS. Disclosures: No relevant conflicts of interest to declare.

Pre-Transplant Salvage Therapy Prior to Autologous Transplant (AHCT) in Patients Not Responding to Initial Induction for Multiple Myeloma (MM)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 597-597
Author(s):  
Ravi Vij ◽  
Xiaobo Zhong ◽  
Mei-Jie Zhang ◽  
Sagar Lonial ◽  
Angela Dispenzieri ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Salvage Therapy ◽  
Salvage Chemotherapy ◽  
Novel Agents ◽  
Disease Stage ◽  
Karnofsky Performance Score ◽  
First Line ◽  
Immunoglobulin Isotype ◽  
First Line Therapy ◽  
Line Therapy

Abstract Abstract 597 Back-ground: Planned upfront AHCT after initial induction improves both overall and progression free survival (OS and PFS) for patients with MM in randomized trials. However, it is unclear whether patients with less than partial response after a finite period of initial therapy should receive AHCT immediately or undergo salvage therapy to improve the level of response pre-AHCT. Methods: We addressed this question by querying the CIBMTR (Center for International Blood and Marrow Transplant Research) database. Between 1995 and 2010, 575 patients received upfront AHCT (within 12 mo of diagnosis) for MM after failing to achieve partial or complete response (PR/CR) to initial induction therapy. The 2326 patients who achieved CR/PR pre- AHCT had superior survival and were excluded (Fig 1). The study groups included: the 324 who received additional salvage chemotherapy after non-response to first line therapy (SALVAGE) and then proceeded to AHCT; and 251 who had no additional salvage chemotherapy but proceeded to AHCT immediately (NOSALVAGE). Outcomes of non-relapse mortality (NRM), relapse, PFS, and OS were compared measuring overall survival from diagnosis. Multivariate analysis using Cox proportional hazard models incorporated the following variables: age, gender, Karnofsky performance score, immunoglobulin isotype, stage, serum creatinine at diagnosis, disease status pre-AHCT, conditioning regimen, time from diagnosis to transplant, type of transplant (single/tandem), novel agents (thalidomide/bortezomib/lenalidomide), time-period of transplant and number of lines of pre-transplant therapy (= or > 1 line) on outcomes. Results: Study cohorts were well balanced with respect to age, gender, Karnofsky performance status, immunoglobulin isotype, disease stage. More pts in NOSALVAGE received VAD (60% vs. 47%, p=0.002) for first line therapy and had a base-line creatinine > 1.5mg/dl (27% vs. 17%, p=0.008). In the SALVAGE cohort, 245 (75%) received one, 65 (20%) two and 14 (4%) three salvage regimens. 197/245(61%), 47/65(59%), 2/14 (14%) were sensitive to 1st, 2nd and 3rd line salvage therapies prior to transplant resulting in 55% in SALVAGE achieving CR/PR pre-AHCT. In NOSALVAGE, 93% were in a minimal response or stable disease state and 7% with progressive disease. In SALVAGE, 55% received AHCT after 2004 compared with 38% in NOSALVAGE likely reflecting additional agents available for salvage. The majority of patients in either cohort (>90%) received Melphalan based AHCT and a minority (<20%) planned tandem AHCT. In the SALVAGE cohort, 44% had AHCT <8 months after diagnosis as compared to 74% in NOSALVAGE (P<0.001). Median follow-up for survivors was 61 mo and 68 mo, respectively. Six year NRM (p=1.0), relapse (p=0.2), PFS (p=0.2) or OS (p=0.5) were no different between the two cohorts). On multivariate analysis, a higher creatinine at diagnosis (> 1.5 vs < 1.5) predicted for higher NRM (p=0.008) and inferior OS (p=0.003), and the use of novel agents predicted for lower risk of NRM (HR = 0.37, P=0.04). Since more time elapsed between diagnosis and transplant among patients who received additional salvage chemotherapy, a left-truncated multivariate analysis was performed to reduce this potential waiting time bias. This multivariate analysis produced similar outcomes for TRM, relapse, treatment failure and OS irrespective of whether or not salvage regimens were used (Fig 2). Conclusions: In the setting of upfront AHCT, no additional benefit could be demonstrated for salvage regimens to upgrade response prior to AHCT. Disclosures: No relevant conflicts of interest to declare.

Impact of first-line platinum therapy on survival in patients with platinum-refractory advanced transitional cell carcinoma of the urothelium (TCCU) treated with vinflunine.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15007-e15007
Author(s):  
Ronan Fougeray ◽  
Toni K. Choueiri ◽  
Francesc Pons ◽  
Fabio Augusto Barros Schutz ◽  
Yacine Salhi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Supportive Care ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Line Therapy ◽  
Line Setting

e15007 Background: Standard first-line therapy of advanced TCCU is based on cisplatin-based combinations. In patients deemed unfit to receive CISPLATIN, carboplatin-based or non-platinum combinations are considered. A phase III trial comparing vinflunine (VFL) and best supportive care (BSC) with BSC alone for second-line treatment of advanced TCCU patients demonstrated a survival advantage for VFL+BSC. We studied the impact of the first-line platinum therapy on overall survival in second line setting. Methods: Eligible 357 patients of the phase III study were split in the two following subsets: CISPLATIN (Patients with prior CISPLATIN administration) and NO CISPLATIN (patients without prior CISPLATIN administration). Survival was measured from the date of random assignment. Overall Survival (OS) was calculated using Kaplan-Meier method, with log-rank comparisons. Multivariate Analysis of OS was analyzed with the Cox proportional hazards model, including prognostic factors for second-line setting previously identified (Bellmunt, 2010). Updated survival data in 11/2008 cut-off date was used. Results: CISPLATIN group represented 70.3% (n=251) and NO CISPLATIN 29,7% (n= 106). CISPLATIN group had less Liver involvement (25% vs 43%, p=0.0007) and better WHO-PS (>1: 66% vs 76%; p=0.0478). OS was higher in CISPLATIN group for all eligible patients (HR: 0.77; CI 95% 0.61-0.97; p=0.0294), for VFL+BSC arm (HR: 0.78; CI 95% 0.59-1.02; p=0.0693) and for BSC arm (HR: 0.68; CI 95% 0.42-1.08; p=0.0978). Multivariate analysis including prognostic factors (liver involvement, hemoglobin, PS) and prior platinum administration, did not show effect of CDDP on OS. VFL reduced the risk of death by 24% in CDDP-group (HR: 0.76; CI 95% 0.58-0.99; p=0.043) and by 35% in NO CDDP –group (HR: 0.65; CI 95% 0.41-1.04; p=0.0724). Conclusions: Differences in prognostic factors between CISPLATIN and NO CISPLATIN groups may explain the differences in OS in patients who undergo 2nd line therapy. The choice of Cisplatin or no Cisplatin chemotherapy in the first line did not impact subsequent benefit of vinflunine over best supportive care.

Prognostic Significance of PET Imaging in Relapsed or Refractory Classical Hodgkin Lymphoma Treated with Salvage Chemotherapy and Autologous Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3417-3417
Author(s):  
Jacob Smeltzer ◽  
Amanda F Cashen ◽  
Qin Zhang ◽  
Camille N. Abboud ◽  
John F. DiPersio ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Pet Imaging ◽  
Salvage Therapy ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Classical Hodgkin Lymphoma ◽  
Front Line ◽  
Free Survival ◽  
Line Therapy

Abstract Abstract 3417 Poster Board III-305 Standard treatment for classical Hodgkin lymphoma (cHL) that has relapsed or is refractory (rel/ref) after front-line therapy consists of standard dose salvage chemotherapy followed by high dose chemotherapy with autologous stem cell transplantation (ASCT). However, the long-term disease free survival in rel/ref cHL patients utilizing this approach is heterogeneous. A number of prognostic factors have been identified retrospectively, with the goal of defining patients that achieve long term remission with ASCT and those with a high risk of relapse. We examined 106 rel/ref cHL patients that underwent ASCT at Washington University from January 2001 to December 2007 with comparable salvage and ASCT therapy. We focused on the 77 patients that had a PET or PET/CT scan pre-ASCT following 2-4 cycles of standard salvage therapy. PET imaging reports were reviewed and interpreted as negative (42%) or positive (58%), with a positive PET conservatively defined as any abnormal residual FDG uptake at a site of prior disease. Median age was 34 (18-70) years with 39% females, median follow-up from ASCT was 38 (range 0.5-85) months. Front-line therapy consisted of ABVD (82%), Stanford V (7%), MOPP/ABV (4%), RT only (3%), or other (4%). High dose conditioning consisted of BEAM (99%) or BEAC (1%). At the time of relapse, stage was I (7%), II (44%), III (24%), or IV (25%). Prognostic factors originally identified by Moskowitz et al. at the time of relapse were 1st remission duration < 1 year (65%), presence of B symptoms (36%), or presence of extranodal disease (27%); these yielded scores at the time of relapse of 0-1 (62%), 2 (28%), or 3 (10%). The German relapsed Hodgkin prognostic score factors (rHPS; 1st remission duration ≤ 1 year, stage III/IV at relapse, anemia at relapse) were available in 75 patients, resulting in scores of 0 (16%), 1 (47%), 2 (28%), or 3 (9%). The modified 4 factor IPS score at relapse reported by Bierman et al. (albumin < 4 g/dL, age ≥ 45 years, anemia, lymphocytopenia) in the 65 patients with these data available was 0 (52%), 1 (35%), 2 (11%), 3-4 (2%). The response to salvage therapy based on PET and CT report when available was CR (42%), PR (46%), SD (5%), or PD (7%). The 2 year event free survival (EFS) and overall survival (OS) for 77 patients with a pre-ASCT PET was 63% and 87% respectively, and the 5 year EFS and OS was 52% and 78% respectively. In univariate analysis positive PET imaging post-salvage therapy was a significant adverse factor on EFS (P=0.005), with a non-significant trend for OS (P=0.133). The 2 year EFS and OS for PET positive patients was 47% and 81%, and the 2 year EFS and OS for PET negative patients was 87% and 100% (see figure). Multivariate analysis indicated that the PET imaging result (P=0.007, HR 3.7, 95%CI 1.43-9.39) and the Moskowitz score (P=0.04, HR 1.84, 95%CI 1.03-3.30) were significantly associated with EFS, while the modified 4 factor IPS (P=0.43) and the rHPS (P=0.44) were not significant. We conclude that PET imaging results, even with a conservative interpretation that any residual abnormal uptake is positive, facilitate prediction of EFS following standard salvage chemotherapy and ASCT in rel/ref cHL patients. A substantial number of PET positive patients by the criteria used in this study were successfully treated with salvage chemotherapy and ASCT. Future studies are warranted to define PET imaging as a prognostic factor prospectively in rel/ref cHL, and uniform standards to assess PET imaging as positive or negative are needed. Disclosures DiPersio: Genzyme: Honoraria.

Treatment Outcomes and Prognostic Factors of Ifosfamide, Etoposide, Cytarabine, Methotrexate, and Dexamethasone (IVAMdex) Regimen As 3rd Line (2nd salvage) Chemotherapy in Patients with Relapsed or Refractory Non-Hodgkin's Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2685-2685
Author(s):  
Yong Park ◽  
Seh Jong Park ◽  
Seok Young Lee ◽  
Se Ryeon Lee ◽  
Hwa Jung Sung ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Febrile Neutropenia ◽  
Confidence Interval ◽  
Treatment Outcomes ◽  
Performance Status ◽  
Univariate Analysis ◽  
Early Death ◽  
Salvage Chemotherapy ◽  
Line Setting

Abstract Abstract 2685 Although high dose chemotherapy with hematopoietic stem cell support is the current standard for patients with relapsed or refractory non-Hodgkin's lymphoma (NHL), all patients are not eligible for this strategy. A portion of this patients experiences refractory or relapsing disease after first salvage. However there are few data for treatment outcomes in this group of patients. In this retrospective analysis we evaluated the efficacy of ifosfamide, etoposide, cytarabine, methotrexate plus dexamethasone (IVAMdex) regimen in 2nd salvage (3rd line) setting and analyzed the pretreatment factors for patients who would be beneficial for this 2nd salvage regimen. A total of 41 patients with relapsed or refractory NHL after 1st salvage chemotherapy were analyzed. All patients were treated with IVAMdex regimen which consisted of ifosfamide (1500 mg/m2 daily from day 1 to day 5), mesna (1500 mg/m2 daily from day 1 to day 5), etoposide (150 mg/m2 daily from day 1 to day 3), cytarabine (100 mg/m2 daily from day 1 to day 3), methotrexate (3 g/m2 on day 5), leucovorin rescue (100 mg/m2 daily from day 5 to day 7), and dexamethasone (40mg on day 1 to day 3). The response rate was assessed after a minimum of two courses of chemotherapy. Toxicity and survival were analyzed in all patients. The median age was 51 years. Performance 0–1 and 2 was 56% and 44%, respectively. 28 evaluable patients completed more than 2 cycles. 13 patients were not evaluated due to early death (n=10), death without response evaluation (n=2), and follow-up loss (n=1), respectively. The overall response was as follows: 9 complete remission (32%), 4 partial remission (14%), 2 stable disease (8%), and 13 progressive disease (46%). The median overall and progression-free survival was 185 days (95% confidence interval, 84 days to 285 days) and 119 days (95% confidence interval, 30 days to 207 days), respectively (Figure 1). Univariate analysis of pretreatment factors for overall survival showed increased LDH (p=0.001), presence of B symptom (p=0.001), chemosensitive disease to prior regimen (p=0.044), performance status 0–1 (p=0.003), and low/low-intermediate IPI group (p=0.017) were significant. Multivariate analysis by Cox regression method showed that increased LDH (p=0.028, harad ratio 3.47, 95% confidence interval 1.147 to 10.526) and performance status 0–1 (p=0.041, hazard ratio 0.35, 95% confidence interval 0.13 to 0.96) were independently significant factor for overall survival. Treatment-related mortality (TRM) was reported in 16 patients (39%) and the cause of all TRMs was infection associated with febrile neutropenia. Of these, 10 deaths (63%) occurred within 30 days after initiation of chemotherapy (early death). Univariate analysis of pretreatment factors for early death showed increased LDH (p=0.011) and presence of B symptom (p=0.017) were significant. However multivariate analysis by log-rank test did not show any independently significant factors for early death. In this study salvage chemotherapy with IVAMdex regimen in 3rd line setting showed moderate response with high toxicities. However, we discovered that there might be subgroup of patients who can benefit from this regimen and serum LDH level and presence of B-symptoms may be useful indicators in differentiating these patients. However, considering high toxicities, the strategy to prevent early death associated with febrile neutropenia should be required. It might include prophylactic G-CSF and antimicrobial agent administration. To draw the conclusion, validation should be warranted in prospective trial with large scale. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The first-line therapy of aggressive non-Hodgkin’s lymphomas in russian clinical practice: data from the EQUILIBRIUM study

2020 ◽  
Vol 15 (2) ◽  
pp. 10-18
Author(s):  
L. G. Babicheva ◽  
I. V. Poddubnaya
Keyword(s):  
Overall Survival ◽  
Clinical Practice ◽  
Complete Remission ◽  
B Cell ◽  
Long Term Results ◽  
First Line ◽  
Therapy Efficacy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Hodgkin's Lymphomas

The objective: evaluation of effectiveness of the first-line therapy with rituximab of B-cell lymphoproliferative diseases in Russian clinical practice in the period from 2014 to 2017.Materials and methods. The EQUILIBRIUM post-registration multicenter study included 1000 patients aged 21 to 91 years old with a verified diagnosis of B-cell non-Hodgkin’s lymphoma, or chronic lymphocytic leukemia, who received at least 4 cycles of rituximab-containing therapy with Acellbia®. The group of aggressive non-Hodgkin’s lymphomas (aNHL), which is the subject of this article, included 295 patients with a median age of 55.9 years: diffuse B-large cell lymphoma – 87 %, primary mediastinal lymphoma – 11 %, Burkitt’s lymphoma – 1 %. Group characterized by the presence of aggressive clinical signs reflecting the poor prognosis: in the majority of patients, generalized stages were diagnosed (61 %), in half of the cases (50.2 %), extranodal localization of tumor foci was detected (in 32.4 % of patients there were 2 or more). The overwhelming majority of patients (84.5 %) received adequate treatment complying with national and international recommendations (R-CHOP, R-CHOEP and R-EPOCH, high-intensity NHL-BFM-R, R-HyperCVAD and R-MACOP-B regimes). The use of R-CVP, FCR, RB, Chl-R, R-monotherapy treatment programs (which received 15.5 % of patients) was considered inadequate for this category of patients.Results. According to the results of the final assessment, high therapy efficacy was established: the overall response exceeded 90 %, complete remission was achieved in most patients with aNHL (68.5 %), partial remission – in every 5th patient (21.8 %). With a median follow-up of 15 months, 16 (5.42 %) deaths and 34 (11.53 %) events were registered. Median of event-free survival and overall survival have not been achieved. Statistically significant differences depending on first-line therapy efficacy were found in overall survival (p = 0.00000) and eventfree survival (p = 0.00000), once again confirming that the main goal of aNHL treatment is to achieve complete remission.Conclusion. Available and compliant with national clinical guidelines treatment of aNHL patients with Russian bioanalogue of anti-CD20 monoclonal antibodies (Acellbia®) demonstrates high immediate efficacy and acceptable long-term results, comparable to a retrospective analysis of previous clinical studies of the original drug rituximab.

Significance of a partial or slow response to front-line chemotherapy in the management of intermediate-grade or high-grade non-Hodgkin's lymphoma: a literature review.

1994 ◽  
Vol 12 (5) ◽  
pp. 1074-1084 ◽  
Author(s):  
R Haw ◽  
C A Sawka ◽  
E Franssen ◽  
N L Berinstein
Keyword(s):  
Median Survival ◽  
Combination Chemotherapy ◽  
Salvage Therapy ◽  
Progressive Disease ◽  
Survival Duration ◽  
High Grade ◽  
Slow Response ◽  
Front Line ◽  
Line Therapy ◽  
Line Chemotherapy

PURPOSE The purpose of this review was to assess the outcome of patients with non-Hodgkin's lymphoma (NHL) who achieve an incomplete or slow response to front-line chemotherapy and to determine whether salvage treatment with intensive combination chemotherapy with or without autologous bone marrow transplantation (ABMT) is successful in such patients. METHODS A comprehensive literature search of studies using combination chemotherapy for the front-line therapy of advanced-stage intermediate- and high-grade NHL and for salvage therapy of patients with a partial response (PR) was reviewed. RESULTS The median survival duration of patients with a PR ranged between 5 to 14 months, while the median survival duration of patients with a complete response (CR) was not reached in many studies. For patients in CR, the probability of survival at 24 months ranged between 0.79 to 1, while for patients in PR it ranged from 0 to 0.31. The rapidity of a response to front-line therapy was often found to be of prognostic importance. Patients who relapsed after a PR to front-line therapy had similar outcomes to intensive salvage therapy as those who relapsed after a CR. ABMT performed immediately after a PR to induction therapy, before progressive disease occurred, resulted in high CR rates in nonrandomized studies. CONCLUSION Patients with aggressive NHL who experience a PR or who respond slowly to front-line chemotherapy have a poor prognosis. Early introduction of dose-intensive salvage therapy before the development of progressive disease may benefit patients with a PR and requires testing in randomized clinical trials.

Front-Line Consolidation with Autologous Stem Cell Transplantation in Patients with Nodal Aggressive Peripheral T-Cell Lymphoma (PTCL). A Prospective Study of the GEL-TAMO.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2463-2463
Author(s):  
Jose Rodriguez ◽  
Eulogio Conde ◽  
Antonio Gutierrez ◽  
Reyes Arranz ◽  
Angel Leon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Salvage Therapy ◽  
Front Line ◽  
Free Survival ◽  
Line Therapy ◽  
Gallium Scan

Abstract Background: Nodal aggressive PTCL have a poor prognosis with conventional chemotherapy regimens for aggressive non-Hodgkin lymphomas. Therefore innovative approaches are needed. Among them, strategies including consolidation with high-dose chemotherapy and autologous stem cell transplantation in front line therapy may improve the outcome of these diseases. Aim: To report the experience of a national cooperative group in 26 patients with aggressive nodal PTCL who underwent treatment including ASCT as consolidation of front line therapy. Patients and Methods: Twenty-six patients Gallium scan positive with nodal PTCL entered into the study: 11 cases of PTCL-unspecified (42%), 8 ALCL (31%) and 7 AIL (27%). Patients received three courses of MegaCHOP and subsequently were evaluated by CT scan and Gallium scan. Those patients Gallium scan negative received another course of MegaCHOP and then the transplant. Those patients Gallium scan positive after 3 courses of MegaCHOP received 2 courses of the IFE regimen (Ifosfamide 3.3g/m2 days 1–3 and Etoposide 300 mg/m2 days 1–3) and if at least achieved a partial response received the transplant otherwise they are out of the study. Median age was 44 years, 96% of the patients presented Ann Arbor stage III or IV; 54% presented B symptoms; 31% bone marrow involvement and 72% of the patients presented 2–3 factors of the a-IPI. Results: Thirteen patients (50%) achieved a CR after 3 courses of MegaCHOP and 12 patients received IFE as salvage therapy. Twenty patients out of the 26 initial patients were able to proceed to the transplant. After the transplant 85% of patients achieved a CR. The 6 patients who did not received the transplant was due to progression of the disease in 4 cases, lethal toxicity in one case and refusal in another case. With a median follow up of 35 months for alive patients, the overall survival (OS) and progression-free survival (PFS) at 3 years were 73% and 53%, respectively. OS, PFS and disease-free survival for the 20 patients who underwent the ASCT consolidation was 84%, 53% and 63%, respectively. Conclusion: Early salvage therapy for patients not in CR after 3 courses of chemotherapy and ASCT consolidation for chemosensitive patients may improve the outcome of patients with nodal aggressive PTCL. Larger series and longer follow up are needed to confirm this promising approach.

Fludarabine Monophosphate as First Line Therapy for Chronic Lymphocytic Leukemia (CLL) - 11 Years Clinical Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4970-4970
Author(s):  
J.E. Novoa ◽  
A.L. Rojo ◽  
B. Beñaran ◽  
R. Draper ◽  
H. Calvo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Monoclonal Antibodies ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Response Rate ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Intravenous Formulation

Abstract Background: fludarabine (F) has become the standard first line therapy for chronic lymphocytic leukemia (CLL) in younger patients. Treatment of early stage patients with chlorambucil without risk stratification has not been shown to prolong survival. In recent years effective and potentially curative approaches such as nucleosides analogues, stem cell transplantation or monoclonal antibodies have been developed. The attraction of monoclonal antibodies is based on selective targeting of tumor - relevant surface markers and a distinct mechanism of action (antibody-dependent cellular cytotoxicity). Aims: to assess the efficacy, safety and quality of life of F in previously untreated B-cell CLL patients in a group of medical institutions in Uruguay during 11 years (1995–2006). Methods: 168 patients between the period 1995 – 2006 were evaluated.120 of them received F intravenous formulation (1995–2006) and 48 the oral one (2002–2006). Age: 48 – 85 years old, media 67 years old. Gender: male 90, female 78. Inclusion criteria for B-cell CLL was Binet stages B, C and A progressive (Ap), 18 to 85 years old, non multiorganic failure, performance status 0 – 2 (WHO), written informed consent. First condition was non previous treatment. Staging: Binet A 12/168, B 116/168 & C 40/168. Treatment: as first line therapy all the patients received (minimum): 6 cycles of i.v. Fludarabine (Fludara®, Schering) 25 mg/m2/daily (5 days) e/30 days or Oral Fludarabine, 40 mg/m2/daily (5 days), 6 cycles. Results: on this B-cell CLL cohort the overall response rate (ORR) was 78% (CR+PR), 80% of them have immunophenotypic response. Safety: on the 1100 cycles in 168 patients, the toxicity was: 1 AIHA, 2 pancytopenia, 3 plaquetopenia. Grade 3–4 infection rate was 1,3%. No alopecia was observed in any patient. Kaposi sarcoma (0,7%). Mortality rate: 1,7% (3/168 patients). Other adverse factors to overall survival were, age over 65 (p=0,0001) and hepatic impairment (p=0,0001). Toxicity: (WHO>2): granulocytopenia 28%, thrombocytopenia 8%, infection 2%. Although fludarabine-treated patients experienced more significant myelosuppression, no difference in the treatment group was demonstrated. Causes of death: Richter 12%, sepsis 5%, associated disease 34%, second malignancy 17% and others 30%. Comparing oral with intravenous formulation in overall survival the results were: CLL 34% vs 36% (p= NS). Conclusions: fludarabine monofosfate (Fludara®) looks like an effective and safe treatment for B-cell CLL. The oral and intravenous formulations have a similar response rate in elderly and young patients. The challenge remains to integrate new information to apply novel therapies in a disease-specific and risk-adapted maner. A longer follow up and a larger trial, might be needed to confirm these results.

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