Efficacy and Safety of Liposomal Cytarabine as Intrathecal Prophylaxis in Patients with Diffuse Large B Cell Lymphoma at High Risk of CNS Involvement: A Multicentric Study Including 80 Patients in Spain.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1663-1663
Author(s):  
Adolfo de la Fuente ◽  
Antonio Salar ◽  
Carlos Panizo ◽  
Belen Navarro ◽  
Teresa Olave ◽  
...  

Abstract Abstract 1663 Poster Board I-689 Introduction Lymphomatous meningitis (LM) in patients with Diffuse Large B Cell Lymphoma (DLBCL) is usually an early complication and with poor prognosis. Risk factors have been previously identified for this complication. DepoCyte is an extended released liposomal cytarabine formulation (LC) which has demonstrated better efficacy compared to standard cytarabine for the treatment of LM in one randomized clinical trial. Purpose and Methods A retrospective study was carried out in 24 Spanish sites including patients diagnosed of DLBCL and at risk of LM – defined by the presence of at least one of the following: retroperitoneal mass ≥ 10 cm; Waldeyer ring, sinus, vertebral or bone, and testicular involvement; LDH more than twice the upper normal limit; bone marrow involvement > 30% and serology VIH+. All patients had received LC as IT prophylaxis for LM in the period April 2005 – June 2009. Main endpoints were effectiveness (leptomeningeal involvement rate) and safety of the IT prophylaxis. Results Data from 80 patients were analyzed. Baseline characteristics were: Mean age 55 ± 16 years (range: 18-80 years). Males 74%; Ann Arbor stage IV 54%. All patients received alkylating based regimens, being R-CHOP as the most frequent one (88%). LC was administered as intrathecal prophylactic treatment for LM in all patients. 64 patients completed the IT prophylaxis treatment with a mean of 2,8 ± 0,83 administrations and a median follow up of 17 months (range: 3-40 months) (8 patient still on treatment and 8 patients died before finish prophylaxis). Just one patient (1,6%) had leptomeningeal spread: 76 years old man with primary testicular DLBCL, treated with R-CHOP regime, who did not reach complete response and died after 8 months of follow up due to respiratory failure. Twenty four patients out of eighty (30%) showed adverse events, being headache the most frequent side effect (27%), and 14% grade IV. Headache was reversible in all cases. Chemical arachnoiditis prophylaxis was given to 70 patients. Conclusions This retrospective study has shown that in DLBCL patients and high risk of LM, prophylaxis with LC was feasible and well tolerated. With a median follow up of 17 months (range: 3-40 months) the incidence of LM was 1,6 %. Prospective, randomized comparative studies versus conventional prophylaxis regimes are needed. Disclosures Off Label Use: DepoCyte is an extended released liposomal cytarabine formulation (LC) which has demonstrated better efficacy compared to standard cytarabine for the treatment of LM in one randomized clinical trial. Prphylaxis effectiveness..

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3056-3056 ◽  
Author(s):  
Jose Rodriguez ◽  
Eulogio Conde ◽  
Antonio Gutierrez ◽  
Juan Carlos Garcia-Ruiz ◽  
Juan Jose Lahuerta ◽  
...  

Abstract From 1985 to 2006, 71 patients with primary mediastinal large B-cell lymphoma receiving induction doxorubicine-based chemotherapy followed by ASCT as front-line therapy were registered in the GEL-TAMO (Spanish Group for Lymphoma and Autologous Transplantation). Median age was 28 years, 56% of patients were female, 40% presented with an ECOG ≥ 2; B-symptoms at diagnosis were present in 25% of the patients. Most patients presented with high-risk clinical features: bulky tumours defined as ≥10 cms of diameter were observed in most patients (87%), high LDH in 72% and, as previously reported (Rodriguez et al, Ann Oncol, 1994), β2m was elevated only in 7% of the cases. Forty-seven percent of patients presented 2–3 risk factors of the a-IPI. At transplant, thirty-five patients (49%) in first complete remission (CR), 23 (33%) in partial response and 13 patients (18%) failing the first induction therapy were transplanted, respectively. Conditioning regimens were BEAM or BEAC in 90% of the patients. 39 patients received Radiotherapy: 19 prior and 20 after the transplant. Most patients (91%) received peripheral stem cells. Only a patient failed to engraft after the transplant. After the transplant 73% of the patients achieved a CR and 17 patients were refractory. With a median follow-up from transplantation of 46,5 months the OS, PFS and DFS are 68%, 59% and 81% respectively. Progression of the disease was the main cause of death (78%). A patient died of a second neoplasia and 3 patients died of sepsis. There were no deaths related to transplant toxicity. By multivariate survival analysis both status of the disease at transplant (CR vs PR vs failure) and the Tumor score (Rodriguez et al, Ann Oncol,1992 ) were the only independent variables associated with the OS and PFS, respectively. In conclusion our experience, with a prolonged follow-up, shows that patients with primary mediastinal large B-cell lymphoma presenting at diagnosis with high-risk features have an encouraging survival and PFS with front-line ASCT. However, patients who received the transplant having failed the induction regimen have a very poor prognosis and should be tested with another innovative approach.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4414-4414
Author(s):  
Daniel O Persky ◽  
Thomas P. Miller ◽  
Joseph M Unger ◽  
Catherine M. Spier ◽  
Soham D. Puvvada ◽  
...  

Abstract Introduction: Patients with limited stage aggressive B-cell non-Hodgkin lymphoma (LS-NHL) and at least one stage-modified adverse risk factor have an excessive relapse rate leading to a 5-year overall survival (OS) of 50-77% and 10-year OS of 0-50%. In SWOG S0014 we have shown that the addition of rituximab to 3 cycles of CHOP plus involved field radiation therapy (IFRT) resulted in an improved estimated 4-year progression-free survival (PFS) of 88% and OS of 92%. Relapses were largely systemic (5 of 6 evaluable) and continued to be seen with longer follow-up. Ibritumomab tiuxetan (Zevalin ®) is a radiolabeled anti-CD20 antibody that has excellent single agent activity in diffuse large B-cell lymphoma and could prevent systemic relapse of disease. We now report long term results of SWOG S0313, a phase II study of ibritumomab tiuxetan consolidation after 3 cycles of CHOP plus IFRT in patients with LS-NHL. Methods: Patients with LS-NHL and at least one stage-modified adverse risk factor (non-bulky stage II, age > 60 years, elevated LDH, or WHO performance status of 2) were treated with CHOP on days 1, 22, and 43, followed 3 weeks later by 40-50 Gy of IFRT. Ibritumomab tiuxetan regimen was initiated 3 – 6 weeks following IFRT. Results: Forty-six patients were registered and eligible, with median follow-up of 7.3 years. Median age was 61, 37% of patients had elevated LDH, and 20% had systemic symptoms. Grade 4 adverse events occurring more than once included neutropenia (8 patients), leukopenia (5), and lymphopenia (2). Febrile neutropenia was observed in 4 patients. No cases of treatment-related myeloid neoplasms were noted. Eleven patients progressed and 8 patients died. The PFS estimate is 89% at 2 years, 82% at 5 years, and 75% at 7 years. OS estimate is 91% at 2 years, 87% at 5 years, and 82% at 7 years. These outcomes compare favorably to matched cohorts on prior SWOG trials, with 7-year PFS estimate of 68% on S0014 and 65% on S8736 (original pre-Rituximab trial); and 7-year OS estimate of 80% on S0014 and 73% on S8736 cohorts. Conclusions: Patients with high-risk LS-NHL treated with 3 cycles of CHOP plus IFRT followed by ibritumomab tiuxetan consolidation had outcomes that compare favorably to our historical experience. A US cooperative group study of R-CHOP and response-adapted IFRT followed by consolidative ibritumomab tiuxetan is ongoing. Disclosures Off Label Use: ibritumomab tiuxetan in diffuse large B-cell lymphoma.


2018 ◽  
Vol 07 (03) ◽  
pp. 200-202 ◽  
Author(s):  
Ajay Gogia ◽  
Chandan K. Das ◽  
Lalit Kumar ◽  
Atul Sharma ◽  
Akash Tiwari ◽  
...  

Abstract Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma. We conducted a retrospective study to analyze the clinicopathological characteristics, cell of origin, response to therapy, and the outcome of patients with DLBCL. Materials and Methods: This was a retrospective study which included all patients with DLBCL registered at our center, between May 1, 2013, and July 31, 2015. The data regarding demography, clinical presentation, histopathology, stage, prognostic index, treatment, and treatment-related outcome were collected from prospectively maintained clinical case records of the patients. Results: In the study, we included 267 patients. The median age is 49 (20–81) years with male: female ratio of 2:1. B symptoms were seen in 124 (45%) of patients. Early Stages (I and II) were seen in 130 (52%) patients, while advanced Stages (III and 1V) were seen in 119 (48%) patients. Bulky disease (>7.5 cm) was seen in 30% of cases, and bone marrow was involved in 12%. Extranodal involvement is present in 35% of cases. Cell of origin data was available in 160 (60%) of cases, of which 88 (55%) were germinal center and 72 (45%) were activated B cell in origin. The distribution according to the international prognostic index (IPI) was as follows: low risk 40%, intermediate risk 45%, and high risk in 15%. Rituximab was used in 45% of cases. The overall response rate was 84% with a complete response (CR) rate of 70.5%. The CR rates were better with RCHOP compared with CHOP (77% vs. 61.5%, P = 0.001) and good-risk IPI (83.3% vs. 65.2%, P < 0.001) compared with intermediate- and high-risk IPI. Median follow-up period was 24 months, and 2-year event-free survival (EFS) was 70%. The presence of B symptoms, high IPI, failure to attain CR, poor PS, and nonrituximab-based chemotherapy were significantly associated with lower EFS. Conclusions: This is the first study from India, which investigated the impact of chemotherapy with or without rituximab in context of cell of origin. Adding rituximab to CHOP showed better response rate and EFS irrespective of cell of origin.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 891-891 ◽  
Author(s):  
Manuela Zanni ◽  
Massimo Di Nicola ◽  
Caterina Patti ◽  
Claudia Castellino ◽  
Alessandra Pescarollo ◽  
...  

Abstract Recent trials have shown that anti-CD20 monoclonal antibody Rituximab may be effectively employed in association with high-dose (hd) chemotherapy and peripheral blood progenitor cell (PBPC) autograft in the management of high-risk B-cell lymphoma. Addition of Rituximab has a dual effect: increased tumour cytoreduction and in vivo purging prior to PBPC harvesting. We here report the results of a prospective, multicenter trial evaluating Rituximab-supplemented hd-sequential chemotherapy (R-HDS) as frontline treatment in patients with high-risk Diffuse Large B-Cell Lymphoma (DLBCL). So far, 6 Italian Centres associated to GITIL have participated to the study. Eligibility criteria included: i. biopsy-proven DLBCL, with CD20+ phenotype; ii. no previous cytotoxic treatments; iii. age between 16–60 yrs.; iv. advanced stage disease with 2–3 aaIPI score. The R-HDS regimen includes an initial debulkying (3 APO courses) and then the sequential administration, at 15–20 day intervals, of: i. cyclophosphamide (CY) 7gr/sqm (day 1) + Rituximab 375mg/sqm (day +2 and +10), followed by PBPC harvest; ii. Ara-C 2gr/sqm b.i.d. for 6 days, reinfusion of 1–3x106 autologous CD34+ve cells/kg (day 7) and then Rituximab 375mg/sqm (day +8 and day +18); iii. etoposide 2.4gr/sqm day +1 + Cisplatin 100mg/sqm day +2; iv. a final myeloablative regimen (Mitoxantrone 60mg/sqm + L-Pam 180mg/sqm), with PBPC autograft (≥5x106 CD34+ve cells/kg) + Rituximab 375 mg/sqm (day +30 and +37); v. involved-field radiotherapy on areas of previous bulky lesions or residual lesions, within 2–3 mos. following autograft. Presently, 91 patients (median age: 48 yrs.) have been enrolled and are evaluable. They all had 2 (58) or 3 (33) aaIPI score; in addition, 63 (69%) presented with disease-related symptoms, 52 (57%) had extranodal disease, and 27 (30%) had BM involvement. There were 4 early toxic deaths (three due to sepsis following CY, Ara-C and autograft, respectively, and one due to leucoencephalopathy from JC-virus infection 2 mos. after autograft); one more toxic death due to pneumonia occurred at 10 mos. after R-HDS, for an overall TRM of 5.5%. In addition, 21 patients had CMV or VZV reactivation that resolved after antiviral therapy. Overall 73 patients (80 %) reached CR. So far, at a median follow-up of 24 mos., 76 patients (83.5%) are alive and 68 (75%) are in continuous CR (CCR), with 4.3-yr OS and and EFS projections of 80% and 74%, respectively. There was a trend towards a better outcome in aaIPI 2 vs. 3, although the difference was not statistically significative. Among 27 patients with BM+, 17 (63%) are presently in CCR, at a median follow-up of 25 mos. In conclusion, R-HDS was feasible at the multicenter level although the occurrence of severe infectious complications should not be underestimated. Nevertheless, both CR rate and survival curve projections compare favorably with the poor outcome usually observed in aaIPI 2–3 patients managed with conventional chemotherapy. The results here presented urge a comparative analysis between conventional vs. intensified Rituximab-supplemented chemoimmunotherapy in younger patients with high-risk DLBCL.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4459-4459
Author(s):  
Miguel A. Canales ◽  
A. Salar ◽  
J.A. Diaz ◽  
J.J. Ferreiro ◽  
S. Ferrer ◽  
...  

Abstract Patients with diffuse large B-cell lymphoma (DLBCL) who develop lymphomatous meningitis (LM) during or after first-line treatment have a poor prognosis, with CNS relapse occurring within 1 year in approximately 80%. Risk factors have been defined and prophylaxis is recommended in patients with high-risk DLBCL. Liposomal cytarabine (DepoCyte®), a sustained-release preparation of cytarabine for intrathecal (IT) injection, has been shown to be well tolerated and effective in the treatment of LM. Its long CSF half-life allows liposomal cytarabine to be given less frequently than conventional therapy, reducing discomfort for patients and the risks associated with repeated lumbar punctures. The potential of liposomal cytarabine to improve the outcome of prophylaxis against LM is being investigated into a multicenter and prospective trial in patients with high-risk DLBCL in Spain. Preliminary safety results are reported in 22 patients (median age 67 years; range 18–79; 14 male) with newly diagnosed DLBCL at high risk of developing LM (defined as the presence of at least one of the following criteria: retroperitoneal mass >10 cm, Waldeyer’s ring or paranasal involvement, involvement of >30% bone marrow, testicular involvement) who received prophylactic IT liposomal cytarabine during treatment with R-CHOP14 regimen between June 2006 and July 2007 at 10 centers in Spain. Liposomal cytarabine 50 mg was administered during the first day of treatment at first, second and sixth cycles of R-CHOP14 scheme (study days 1, 15 and 71). The median number of doses administered was 3 (range 1–3). Seventeen patients received corticosteroid as prophylaxis for chemical arachnoiditis: 16 dexamethasone (4 mg IT [n = 9] or PO at varying dosages [n = 7]); and 1 patient received IT hydrocortisone (20 mg). The remaining patients did not receive specific corticosteroid prophylaxis for chemical arachnoiditis. Overall, liposomal cytarabine was well tolerated. Six patients experienced minor side effects including headache (Grade 1/2, n = 4; grade 3/4, n = 2) and nausea/vomiting (Grade 3/4, n = 1). No signs of neurological progression or relapsed were observed. These preliminary observations indicate that IT injection of liposomal cytarabine (DepoCyte®) is well tolerated and can be administered safely in combination with dose-dense regimens. Longer-term follow-up will be needed to confirm these encouraging observations.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 136-136 ◽  
Author(s):  
Matthew J Maurer ◽  
Ivana N Micallef ◽  
Jerry A Katzmann ◽  
Daniel Nikcevich ◽  
Thomas E Witzig

Abstract Abstract 136 Background: The serum free light chain (FLC) assay quantitates free kappa and free lambda immunoglobulin light chains. This assay has prognostic value in MGUS, multiple myeloma (MM), solitary plasmacytoma, and AL amyloidoisis, and has been incorporated in response criteria for both MM and AL amyloidosis. A percentage of non-Hodgkin's lymphoma (NHL) patients also present with abnormal FLC concentrations and recent data suggest that AIDS patients with elevated serum FLC are at higher risk of developing NHL. Here we assess the impact of FLC in a cohort of patients with diffuse large B-cell lymphoma (DLBCL) enrolled on a cooperative group clinical trial. Methods: Newly diagnosed DLBCL patients were treated with epratuzumab + R-CHOP (ER-CHOP) on NCCTG clinical trial N0489. Serum FLC was quantitated prior to treatment and after cycles 2 and 6 using the Freelite FLC assay (The Binding Site, Ltd., Birmingham, UK). Patients were followed per clinical trial protocol for event-free (progression, retreatment, or death due to any cause) and overall survival (EFS and OS, respectively). Results: 107 patients were enrolled on the trial. 80 patients had a pre-treatment serum draw and a central pathology confirmed diagnosis of DLBCL, of which 47 had a post-cycle 2 sample (C2) and a 54 had a post-cycle 6 sample (C6). At a medium follow-up of 25 months (range 7-39), 22 patients (28%) had an event and 17 patients died (21%). Prior to treatment 23 patients (29%) had abnormal kappa concentrations (all elevated), 16 (20%) had abnormal lambda concentrations (11 elevated, 5 decreased), and 9 (11%) had an abnormal kappa/lambda ratio. FLC concentrations were significantly reduced in patients during treatment, with a median reduction in kappa (C2: 46%, C6: 64%) and lambda (C2: 44%, C6: 49%), all p<0.0001. Elevated FLC prior to treatment was highly associated with both OS (logrank p=0.009) and EFS (logrank p=0.006); these associations remained significant after adjusting for IPI (both p = 0.01). Conclusions: A significant percentage of DLBCL patients present with abnormal FLC concentrations. Kappa and lambda are significantly reduced for most patients during treatment. Elevated pre-treatment FLC concentrations are associated with inferior EFS and OS in DLBCL and this association is independent of the IPI. A follow-up study of FLC and prognosis is currently underway in a cohort of 1500 NHL patients from the Mayo Clinic and University of Iowa SPORE. Disclosures: No relevant conflicts of interest to declare.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Murat Ozbalak ◽  
M. Cem Ar ◽  
Nukhet Tuzuner ◽  
Ayse Salihoglu ◽  
A. Emre Eskazan ◽  
...  

The aim of this single-center, retrospective study was to investigate the impact of rituximab, reconsider the validity of International Prognostic Index (IPI), and evaluate the prognostic role of the cell of origin (CoO) in a relatively young cohort. Three hundred twelve diffuse large B cell lymphoma patients (median age: 52) were included. Rituximab significantly improved the 3- and 5-year progression free survival (PFS) (70% versus 65% and 41% versus 36%, resp.; P<0.001) but led only to a slight, insignificant increase in 3- and 5-year overall survival (OS) (71% versus 77.3% and %67 versus 74.5%, resp.; P=0.264). In the young, low risk patient subgroup (aaIPI = 0&1; n=129), rituximab improved 3- and 5-year PFS and OS rates (P<0.001 and P=0.048, resp.). The efficacy of rituximab in young high risk patients was comparable to the literature. CoO data were available in 190 patients. The OS at 3 years was 79% for GC and 64% for non-GC subgroups (P=0.014). To the best of our knowledge, this is the first study which investigated the impact of R-CHOP in the context of CoO and IPI in a relatively young cohort. CoO was not an independent risk factor for prognosis in the multivariate analysis although patients with GC showed a significant survival advantage in the univariate analysis. CoO was also found to be a significant determinant of response in refractory/relapsed patients. Our results confirm the efficacy of rituximab in low and high risk, young patients outside of a randomized clinical trial setting.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5077-5077
Author(s):  
Sabir Hussain ◽  
Arif Alam ◽  
Amar Lal ◽  
Hani Y Osman ◽  
Asad Khan ◽  
...  

Abstract Background: Diffuse large B cell lymphoma is the most frequent Haematological Malignancy in UAE. DLBC lymphoma treatment and outcome are well established. Most of reported outcome data is from North America or Europe. Because of lack of reported literature from Middle East, a retrospective data collection and review was performed in Tawam Hospital to evaluate the outcome of DLBC lymphoma. Methods: Retrospective chart review of all diffuse large B cell lymphoma patients treated from January 1, 2008 till December 30, 2012 at Tawam Hospital, a Tertiary Care Oncology Centre in UAE. Results: A total of 99 patients were identified with diffuse large B cell lymphoma. The median age was 48 (17 to 85). 59% of patients were male with a male to female ratio of 1.4. There were 17 (17%) stage I cases, 27 (27%) stage II cases, 23 (23%) stage III cases, and 30 (30%) stage IV cases. The stage was not documented in 2 (2%) patients. International Prognostic Index (IPI) score was documented in 80 (80%) patients. 28 (35%) of patients had low IPI score (0 or 1 risk factor), 33 (41%) patients had low intermediate IPI score (2 risk factor), 8 (10%) patients had high Intermediate IPI score (3 risk factors) and 11 (14%) patients had high IPI score (4 and 5 risk factors). 88 (89%) patients completed planned treatment: either R-CHOP or R-CHOP like chemotherapy. Involved field radiation therapy (IFRT) was given in limited stage and bulky disease. 11 (11%) patients didn't have a complete treatment. 3 patients received only R-CVP, 4 patients received only 1 cycle R-CHOP, 1 patient did not receive any treatment, 1 patient received only palliative Radiotherapy, 1 patient received Rituximab and palliative RT and 1 patient received only Dexamethasone and Rituximab. Relapse-free patients had median follow up of 31 months (1 to 67). 19 (26%) had less than 12 months follow up after completion of chemotherapy. Patients with documented relapses or primary refractory disease had relapse or progression at a median follow up of 14 month (1 to 43). There were 3 (10%) relapses in Low IPI score, 8 (24%) in low intermediate group, 4 (50%) in high intermediate group and 6 (54%) in high risk group. Discussion: Our data showed more young patients, median age 48, as compared to SEER data median age 65 and male predominance (59%), slightly higher as compared to SEER data (55%). These findings may be related to the demographics of UAE. UAE relatively have young and male predominance partly due to large number of expatriate population. Distribution of IPI score in our data is different as compared to the reported data; low risk 35% vs 52%, low intermediate 41% vs 21%, high intermediate 10% vs17%, and high risk 14% vs10%. Our data is missing reporting of IPI score in 20% of cases, may explain party the above difference. As median follow up of patient without relapse was 34 months, so comparison was made with 3 years progression free survival data reported in literature. Relapse free survival in the Low risk group 90% is comparable to reported 3 years progression free survival of 87% , low intermediate 76% as compared to reported 75%, in High intermediate and High risk group 50% and 46% are close to reported 59% (3) and 50% . The difference in high intermediate and high risk group as compared to reported survival in literature may be due to small number of patients in these groups. Conclusion: Outcome of DLBC lymphoma in our single centre retrospective review is relatively similar to reported outcome in literature. Median age is lower as compared to SEER data. Disclosures No relevant conflicts of interest to declare.


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