A Comparison of Beam and Yttrium 90 Ibritumomab Tiuxetan (Zevalin®) in Addition to Beam (Z-BEAM) in Older Patients Undergoing Autologous Stem Cell Transplant (ASCT) for B-Cell Lymphomas: Impact of Radioimmunotherapy on Transplant Outcomes.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3043-3043 ◽  
Author(s):  
Amrita Y. Krishnan ◽  
Auayporn Nademanee ◽  
Andrew Raubitschek ◽  
Henry C. Fung ◽  
Arturo Molina ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Older Patients ◽  
Cell Lymphoma ◽  
Conditioning Regimen ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Bulky Disease ◽  
Significant Difference

Abstract Background: ASCT is an effective treatment for patients with high risk NHL. However, relapse rates remain high. Attempts at further dose intensification are limited by regimen-related toxicity especially in older patients. Zevalin as a single agent has showed activity in aggressive Non-Hodgkin’s Lymphoma (NHL). We therefore, devised a novel conditioning regimen (Z-BEAM) combining standard dose Zevalin (0.4mci/kg) with high dose BEAM (BCNU 150mg/m2 day-7,-6, cytarabine 800mg/m2 and etoposide 800mg/m2 day-5 to day-2, and melphalan 140mg/m2 day-1). Herein, we provide an update on the study and also retrospectively compare this new conditioning regimen with conventional high dose BEAM in older patients (age >=50). Between 1995 and 2005, 65 patients (BEAM n=32, Z-BEAM n=33) underwent ASCT utilizing these regimens. Patient selection was similar for Z-BEAM and BEAM. Patients received BEAM prior to the opening of the Z-BEAM protocol and similiarly after the Z-BEAM protocol completed accrual. The groups were well matched for most demographics and disease status. Median age: Z-BEAM - 62 yrs (range 50–78), BEAM - 64 yrs (range 50–77); 1st CR/PR pts comprised 45% in the Z-BEAM arm and 34% in the BEAM, > =1st Relapse 42% vs 50% and induction failure 12% vs 15%. (p=0.7). Median number of prior regimens was 3 in the Z-BEAM group vs 2 in the BEAM arm.(p=0.08) 54 % had bulky disease at diagnosis in the Z-BEAM group vs 41% in the BEAM group (p=0.30). Results: Two-year OS was 78% for all pts (95%CI, 67–86). Two-year OS/PFS in the Z-BEAM group was 88%(95% CI, 70–95)/72 %(95% CI, 57–83) respectively vs 65% (95%CI, 48–77)/ 67%( 95CI, 50–79) in the BEAM group (Figure1). Analysis by histology showed that in patients with diffuse large B-cell lymphoma (DLBCL), there was a significant difference in OS/PFS of Z-BEAM vs BEAM, 95% vs 48% at 2 yrs (p=.009)/ 88% vs 48% ( p=0.015). The OS/PFS difference of Z-BEAM vs BEAM in patients with mantle cell lymphoma did not reach significance. The toxicity profile and transplant related mortality was similar in both regimens. Conclusions: Our study suggests that the addition of Zevalin to the BEAM conditioning regimen is feasible and well tolerated in older patients. The favorable outcome of patients treated with Z-BEAM compared with BEAM alone, especially in patients with DLBCL, suggests that prospective study in a randomized trial is warranted. Overall Survival 
 ZBEAM versus BEAM Overall Survival 
 ZBEAM versus BEAM

Treatment of Diffuse Large B-Cell Lymphoma with Rituximab, Intensive Induction and High-Dose Consolidation: The Final Analysis of the Czech Lymphoma Study Group (CLSG) R-MegaCHOP-ESHAP-BEAM (R-MEB) Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 21-21
Author(s):  
Marek Trneny ◽  
Robert Pytlik ◽  
David Belada ◽  
Katerina Kubackova ◽  
Ingrid Vasova ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background. Combined immunochemotherapy with CHOP and rituximab have improved the outcome of patients with diffuse large B-cell lymphoma (DLBCL). and related diseases. However, the cure rate of patients with IPI 3–5 or aaIPI 3 is still only about 50% with this regimen. Given the feasibility of previous CLSG regimens based on high-dose CHOP-ESHAP induction and BEAM consolidation, we have conducted a phase II trial combining this approach with rituximab immunotherapy. Patients and methods. Patients aged 18–65 years with DLBCL and age-adjusted IPI (aaIPI) 2–3 were treated with three cycles of high-dose CHOP (MegaCHOP - cyclophosphamide, 3 g/m2, vincristine 2 mg, adriamycin, 75 mg/m2, and prednisone, 300 mg/m2) with G-CSF every 3 weeks, followed by three cycles of ESHAP (etoposide, 240 mg/m2, cisplatin, 100 mg/m2, methylprednisolone, 2000 mg and Ara-C 2000 mg/m2) every 3 weeks. Four to six doses of rituximab 375 mg/m2 were administered on day 1 of each cycle of induction therapy. High-dose therapy (BEAM) followed by autologous stem cell transplant (ASCT) was used as consolidation. Radiotherapy was given to residual masses or sites of bulky disease. Primary endpoint was progression-free survival (PFS), while secondary endpoints were overall survival (OS) and feasibility of the treatment. Results. From April 2002 to October 2006, 105 consecutive patients from 10 centers were recruited. 58% were men and 42% women with median age 46 years (19–63 years). 74% of patients had stage IV disease, 92% had elevated LDH, 53% had performance status >1, 55% had B symptoms and 19% had bone marrow involvement. aaIPI was 2 in 62% of patients and 3 in 38% of patients. 68% of patients received the whole treatment according to the protocol, including ASCT and radiotherapy. Stem cells mobilization according to the protocol was performed in 90% of patients and was successful in 86% of mobilized patients (77% of all patients). 73% of patients ultimately received ASCT (including 3 patients transplanted after ammended treatment) and 51% of patients received planned radiotherapy. Complete remission (CR) was achieved in 83% of all patients and partial remission (PR) in 2%. Early toxic death rate was 6% and 9% patients had primary refractory disease. Of patients who achieved CR or PR, only 6 subsequently relapsed (7%) and two suffered late toxic death (2%). With a median follow-up of 32 months for living patients, the estimated 2-year PFS is 77% and 2-year OS is 81%. Age less than median (46 years) was strongest predictor of favorable outcome (p = 0,00006 for PFS and p = 0,00013 for OS), while there was no effect of stage, LDH, performance status or aaIPI (2-year PFS 79% for aaIPI 2 and 77% for aaIPI 3, 2-year OS 81% for aaIPI 2 and 80% for aaIPI 3). Delivery of ASCT or radiotherapy did not significantly affected PFS in patients who did not suffered early progression or early toxic death, but radiotherapy modestly improved OS of these patients (p = 0,03). Conclusion. R-MEB has proved to be an effective treatment strategy for younger patients with high-risk aggressive B-cell lymphoma. Currently, CLSG is testing whether utilization of early PET scan may decrease toxicity and improve treatment tolerance while maintaining the efficacy of this regimen.

Efficacy of High-Dose Sequential Chemotherapy and Autograft for Transformed Non Hodgkin’s B Cell Lymphoma: Results of a Retrospective Analysis from GITIL (Gruppo Italiano Terapie Innovative nei Linfomi).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3440-3440
Author(s):  
Massimo Di Nicola ◽  
Liliana Devizzi ◽  
Alessandro Rambaldi ◽  
Manuela Zanni ◽  
Fabio Benedetti ◽  
...  
Keyword(s):  
B Cell ◽  
Progressive Disease ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Bulky Disease ◽  
Number Of Patients ◽  
Sequential Administration ◽  
Histological Transformation ◽  
The Impact

Abstract Background - Follicular lymphoma (FL) transforms in a more aggressive lymphoma in 25–60% of patients representing the outgrowth of a more malignant subclone. Transformation is usually associated to a rapidly progressive clinical course, refractoriness to treatment, and short survival. To define the impact of high dose sequential (HDS) therapy and peripheral blood stem cell (PBSC) autograft on outcome of transformed FL (TFL), we analyzed a consecutive series of 66 pts with a confirmed diagnosis of TFL registered at the GITIL centers from March 1988 to September 2004 and treated with the HDS regimen. Methods - Biopsy-proven histological transformation (HT) in diffuse large B cell lymphoma (DLBCL) was observed at diagnosis (n=24; 36%) or at relapse after a treatment for FL (n= 42; 64%). Main patient characteristics were as follows: male/female 36/30; median age 51 yrs (range 33–66), stage I-II/III-IV 8/58, IPI score 0–1/≥2 28/38. HDS regimen included: i. 3 APO or 3 DHAP courses (for patients relapsed after anthracycline-containing regimens); ii. sequential administration of hd-CTX (7g/mq), hd-Ara-C, (2g/mq q12h for 6 days) hd-Etoposide (2.4 g/mq), with PBSC harvests following hd-CY and hd-Ara-C; iii. myeloablative regimen with hd-Mitoxantrone/L-Pam (n=28) or BEAM (n=28 pts who could not receive additional anthracycline), or TBI-PAM (n=3); iv. PBSC autograft; v. consolidation radiotherapy on bulky disease. From January 1999, hd-CTX and hd-Ara-C has been supplemented with Rituximab (RHDS; n=34) with in-vivo purging intent. Results - Overall 59 patients achieved a complete remission (CR; 89%), 1 patient responded partially and underwent allogeniec bone marrow transplantation, 6 patients died for progressive disease while on therapy (PD; 9%). With a median follow-up of 67 months (range 23–170), 42 patients are alive (63.6%), 24 patients relapsed and died for progressive disease (n= 23) or toxicity (n= 1). Five-year event free survival (EFS) and overall survival (OS) are 53.0% and 63.6%, respectively. No significant differences in OS and EFS were observed between patients with HT at diagnosis or at relapse, with IPI O-1 vs IPI >2. Of note, pts treated with R-HDS showed an improved clinical outcome (OS: 76% vs. 50%; EFS: 67.6 vs. 37.5 respectively), with a large difference that did not reach statistical significance because of the limited number of patients. Conclusion - Our data strongly suggest that HDS regimen, in particular when supplemented with rituximab (R-HDS), is a very effective regimen in transformed B cell lymphoma.

Differences in outcomes between patients whose relapse was diagnosed radiologically versus clinically after autologous transplantation for relapsed/refractory diffuse large B-cell lymphoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19001-e19001
Author(s):  
Ghulam Rehman Mohyuddin ◽  
Ashley Elizabeth Clark ◽  
Leyla Osman Shune ◽  
Tara L. Lin ◽  
Sunil H. Abhyankar ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Autologous Transplantation ◽  
B Cell Lymphoma ◽  
Clinical History ◽  
Cell Transplant ◽  
Bulky Disease ◽  
Clinical Cohort ◽  
Large B Cell Lymphoma ◽  
Large B Cell

e19001 Background: Surveillance scans performed after autologous stem cell transplant (AutoSCT) for patients with relapsed/refractory (RR) diffuse large B Cell lymphoma (DLBCL) have no proven survival benefit. We studied survival differences among patients with RR DLBCL post AutoSCT whose recurrences were detected on clinical history and exam, versus those detected on routine surveillance scan. Methods: We retrospectively identified 139 patients from our institutional database with DLBCL who underwent AutoSCT from 2000 to 2014. All patients had surveillance scans performed at days 100, 180 and at 1-year post AutoSCT. Results: Among the 139 patients with RR DLBCL that underwent AutoSCT, 37 relapsed, of which 21 were clinical and 16 radiological. There were no statistically significant differences in patient characteristics, although more patients in the clinical cohort had extra-nodal and bulky disease (Table 1). The median time to progression was 167 days for the clinical cohort and 565 days for the radiological cohort (p= 0.03). Median follow-up was 587 days for the clinical cohort and 1503 days for the radiological cohort (p=0.002). Median overall survival (OS) was 587 days for the clinical cohort, and was not reached for the radiological cohort (p=0.006). Conclusions: In our review, most patients with relapsed DLBCL after AutoSCT were diagnosed clinically. Patients whose relapse was diagnosed clinically were likely to be detected earlier and have a shorter OS. Our data indicates that patients with aggressive disease may be detected when clinically relevant, regardless of scanning. Given the known risks of excess radiation exposure, our data suggests that routine scanning may not be necessary in the majority of patients with DLBCL following AutoSCT. [Table: see text]

A phase III trial evaluating glofitamab in combination with gemcitabine plus oxaliplatin versus rituximab in combination with gemcitabine and oxaliplatin in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS7575-TPS7575
Author(s):  
Mark Hertzberg ◽  
Matthew Ku ◽  
Olivier Catalani ◽  
Betsy Althaus ◽  
Stephen Simko ◽  
...  
Keyword(s):  
B Cell ◽  
Bispecific Antibody ◽  
Clinical Laboratory ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Response Rates ◽  
Phase Iii ◽  
High Dose ◽  
Cell Transplant ◽  
Laboratory Test Results

TPS7575 Background: Prognosis is poor for patients with R/R DLBCL, particularly those who are ineligible for autologous stem cell transplant (ASCT) or who relapse after second-line therapy (Gisselbrecht C, et al. Br J Haematol 2018). While chimeric antigen receptor therapies have shown favorable response rates in R/R DLBCL, convenient off-the-shelf options are needed, especially for patients with rapidly progressing disease (Sermer D, et al. Blood Adv 2020). Glofitamab is a full-length, humanized, immunoglobulin G1 bispecific antibody with two regions that bind to CD20 (B cells) and one region that binds to CD3 (T cells). In an ongoing Phase I study in patients with R/R non-Hodgkin lymphoma, glofitamab monotherapy has induced high response rates with a manageable safety profile (NCT03075696; Hutchings M, et al. ASH 2020). Rituximab in combination with gemcitabine and oxaliplatin (R-GemOx) is widely used for patients with R/R DLBCL who are not eligible for ASCT (Mounier N, et al. Haematologica 2013). Methods: GO41944 (NCT04408638) is a Phase III, open-label, randomized trial designed to evaluate the safety and efficacy of glofitamab plus gemcitabine and oxaliplatin (glofit-GemOx) vs R-GemOx in patients with R/R DLBCL. Eligible patients must be aged ≥ 18 years, have histologically confirmed DLBCL (excluding transformed indolent disease, and high-grade B-cell lymphoma (BCL) with MYC and BCL2 and/or BCL6 rearrangements), and have received ≥ 1 prior systemic therapies; patients who have failed only one prior line of therapy must not be eligible for high-dose chemotherapy followed by ASCT. Prior treatment with GemOx, R-GemOx or a CD20xCD3 bispecific antibody is not permitted. Patients are randomized 2:1 to receive up to eight 21-day cycles of either glofit-GemOx (intravenous [IV], followed by up to four cycles of glofitamab monotherapy) or R-GemOx (IV). A single dose of obinutuzumab is administered seven days prior to the first glofitamab administration. Randomization is stratified by number of prior lines of therapy and outcome of last systemic therapy (relapsed vs refractory). The primary objective is overall survival from time of randomization. Secondary efficacy objectives include progression-free survival, complete and overall response rates, duration of response, and time to deterioration in physical functioning and fatigue, and in lymphoma symptoms. Safety objectives comprise rate of adverse events, change from baseline in targeted vital signs and clinical laboratory test results, and tolerability. Pharmacokinetic, immunogenicity and biomarker endpoints will also be explored. The study started on February 17, 2021; an estimated enrollment of 270 patients by the study completion date of March 2022 is anticipated. Clinical trial information: NCT04408638.

Fas or Fas Ligand Expression Can Determine the Clinical Outcome of Germinal Center Type in Diffuse Large B Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3267-3267
Author(s):  
Yasushi Kojima ◽  
Hisashi Tsurumi ◽  
Naoe Goto ◽  
Michio Sawada ◽  
Toshiki Yamada ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Germinal Center ◽  
Fas Ligand ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Significant Difference ◽  
Type 3 ◽  
Large B Cell

Abstract In recent years, diffuse large B cell lymphoma (DLBCL) has been classified by a cDNA microarray, an oligonucreotide microarray, or a tissue microarray. From the prognostic point of view, DLBCL consists of germinal center B-cell-like (GC) type, activated B-cell-like (ABC) type and type 3. ABC type and type 3 can be collectively categorized as non-GC (NGC) type. GC type has favorable prognosis compared with NGC type. Escape from apoptosis is considered to be an important mechanism for the progression of lymphoma. Fas is the major protein which leads to apoptosis by binding with Fas-ligand (FasL). We evaluated the prognostic significance of such markers as CD10, Bcl-6, MUM1, Fas and FasL, as well as GC or NGC type with paraffin embedded sections from 69 DLBCL patients immunohistochemicaly. The patients were 40 men and 29 women with median age of 67 years old (range, 20–82 years old). The median follow-up of surviving patients was 43 months. The 3-year OS for the entire group was 56%. There was no significant difference in sex, age, clinical stage, lactate dehydrogenase, or International Prognostic Index between GC and NGC type. Expression of CD10 was seen in 29% (20 of 69 of the patients), Bcl-6 in 27% (19 of 69), MUM1 in 27% (19 of 69), Fas in 51% (36 of 69), and FasL in 50% (35 of 69). We divided 69 DLBCLs to 26 GC type (CD10 positive or Bcl-6 positive and MUM1 negative) and 43 NGC type (the other). Positive CD10 was the best marker to indicate favorable overall survival (p=0.0156). GC type had tendency to have better overall survival than NGC type, though it was not significant (p=0.0723). Although Fas or FasL expression was not significant for overall survival in all DLBCL, it predicted significantly a longer over all survival (Fas; p=0.0021, FasL; p=0.0165) in GC type. These results may suggest that the presence of a subtype of DLBCL in which Fas/FasL system works effectively. This group is approximately 20% of DLBCL and mainly belongs to the GC type. Fas expression in GC type of DLBCL may predict the prognosis and be useful to choose the appropriate therapy. Furthermore, CD10 was more significant than GC type and, thus, we may need to build the strict consensus for GC type.

Autologous SCT In Patients (pts) with Chemotherapy-Resistant Diffuse Large B Cell Lymphoma (DLBCL) Followed by Maintenance with Rituximab.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4598-4598
Author(s):  
Rodolfo Calixto ◽  
Mauricio Ostronoff ◽  
Fabiana Ostronoff ◽  
Alexandre Sucupira ◽  
Djenane Manso ◽  
...  
Keyword(s):  
B Cell ◽  
Median Time ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Conditioning Regimen ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
Bulky Disease ◽  
Pseudomonas Infection ◽  
Neutrophil Engraftment

Abstract Abstract 4598 There are few data on the use of maintenance Rituximab after auto-SCT for patients with B cell lymphoma of aggressive histology that are resistant to chemotherapy. From May 2005 to March 2010, 25 consecutive pts underwent auto-SCT for DLBCL resistant to chemotherapy at our center. Median age 43 year (7 – 69 yrs); 11 patients were male. Two pts were HIV positive. Initial staging was II-B in 6 patients, II-EB in 4 patients, III-B 8 patients and IV-B in 7 patients. Initial IPI score was low-intermediate (13% of the pts), high-intermediate (58%) and high (29%). Nine of the 25 pts had bulky disease and 8 had visceral or bone marrow lymphomatous involvement. The median time from diagnosis to auto-SCT was 21 months (13 – 48 m). Prior to auto-SCT, 44% of the patients received 2 chemotherapy regimens and 56% received more than 2. All pts had chemotherapy-sensitive disease to the their last chemotherapy regimen prior to auto-SCT, with 80% and 20% of the pts achieving complete and partial remission prior to transplant, respectively. Sixteen out of 25 pts received Rituximab prior to auto-SCT; of those, 5 received Rituximab in the first line chemotherapy and 11 received it as part of the rescue chemotherapy regimens. The protocol was approved by our institutional review board and informed consent was obtained from each pt and or their guardians. Conditioning regimen consisted of Cyclophosphamide 1500 mg/m2 (D-6 to D-3), Etoposide 400 mg/m2 (D-6 to D-3) and Carmustin 150 mg/m2 (D-6 to D-4). The median CD34+ cells/kg infused was 2.9 × 106/Kg (1.9 - 8.5×106). All pts received G-CSF 10 micrograms/Kg/day SC from day +1 until neutrophil engraftment. Median time to neutrophil engraftment (ANC >500/mm3) was 8 days (5 – 17 d). Median time to platelet recover (>20,000/mm3) was 13 days (7 – 29 d). Transplant related mortality at day +100 was one in 25 pts (4%); this pt died due to multi-drug resistant Pseudomonas infection on day +17. Rituximab 375mg/m2 weekly for 4 weeks was administered as maintenance for a total of 4 cycles (16 doses); the cycles started on days +120, +240, +360 and +480 after auto-SCT. Twelve pts developed mild infusion reaction (tremor and rash). The hematological toxicity was low; grade II neutropenia occurred in 9 out of 25 pts. The neutropenic only occurred after the forth dose of the cycle with a median duration of 5 days (2 - 13). All pts received Bactrim and Acyclovir prophylaxis for one year after the auto-SCT. There were no viral infectious complications. Four of the 25 pts died (16%); one due to Pseudomonas infection; 3 due to relapsed disease which occurred at 6, 9 and 19 months after the transplant. Overall disease free survival was 75% with a median follow up of 31 months (6 - 55 mo). Of the five pts with refractory disease who had received Rituximab at some point prior to transplant, 2 pts relapsed and died due to refractory Lymphoma after the transplant, but 03 are alive in CR (9, 13, 21 months). Our data suggests that the administration of Rituximab as maintenance after auto-SCT for pts with DLBCL is well tolerated and it may decrease the incidence of relapse. Randomized studies are warranted to confirm the benefit of Rituximab as maintenance in the post auto-SCT setting to decrease relapse rate. Disclosures: No relevant conflicts of interest to declare.

IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin's lymphoma.

1997 ◽  
Vol 15 (10) ◽  
pp. 3266-3274 ◽  
Author(s):  
D G Maloney ◽  
A J Grillo-López ◽  
D J Bodkin ◽  
C A White ◽  
T M Liles ◽  
...  
Keyword(s):  
B Cell ◽  
Peripheral Blood ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Clinical Activity ◽  
High Dose ◽  
Low Grade ◽  
Bulky Disease ◽  
Anti Cd20 ◽  
Change In Mean

PURPOSE To evaluate the safety, pharmacokinetics, and biologic effect of multiple doses of the chimeric anti-CD20 monoclonal antibody (mAb) IDEC-C2B8 in patients with relapsed B-cell lymphoma. PATIENTS AND METHODS Twenty patients with relapsed low-grade (n = 15) or intermediate-/high-grade (n = 5) lymphoma received weekly infusions times four of 125 mg/m2 (n = 3), 250 mg/m2 (n = 7), or 375 mg/m2 (n = 10) of IDEC-C2B8. RESULTS Infusional side effects during the initial infusion were mainly grade I/II fever, asthenia, chills, nausea, rash, and urticaria. More serious events were rare. Peripheral-blood B cells were rapidly depleted and slowly recovered over 3 to 6 months. There was no change in mean immunoglobulin (Ig) levels. Antibody serum half-life (and maximum concentration [Cmax]) generally increased between the first and fourth infusions (33.2 hours v 76.6 hours, respectively) following the 375-mg/m2 doses. Six of 18 assessable patients had a partial remission (PR), with a median time to disease progression of 6.4 months (range, 3 to 21.7). Minor responses (MRs) were observed in five patients and progressive disease (PD) in seven. Tumor responses occurred in peripheral blood, bone marrow (BM), spleen, bulky lymph nodes, and extranodal sites, and in patients who had relapsed following high-dose myeloablative chemotherapy. Six of 14 patients (40%) with a low-grade histology responded. Four of six with bulky disease had a PR. CONCLUSION IDEC-C2B8 chimeric anti-CD20 mAb therapy is well tolerated and has clinical activity in patients with relapsed B-cell lymphoma. The 375-mg/m2 dose has been selected for a phase II trial in patients with relapsed low-grade or follicular B-cell lymphoma.

scholarly journals Review of Primary Mediastinal Large B Cell Lymphomas in Our Hospital

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5459-5459
Author(s):  
Kati Hurst ◽  
Maria Cristina Moragues Martinez ◽  
Manuel Espeso de Haro ◽  
Manuel Barrios Garcia ◽  
Ana Isabel Heiniger Mazo
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
B Cell Lymphoma ◽  
Bulky Disease ◽  
Epidemiological Factors ◽  
Consolidation Radiotherapy ◽  
The Impact ◽  
Large B Cell

Abstract BACKGROUND: Primary mediastinal B-cell lymphoma (PMBCL) are a subtype of diffuse large B cell lymphoma (DLBCL), that represent 2-4% of all non-Hodgkin lymphoma (NHL) and 6-12% of DLBCL. They affect young adults with a median age at diagnosis of 35 years old and are more frequent in females (2:1). Approximately 80% of patients have stage I or II disease at the time of diagnosis, with B symptoms, bulky mass and superior vena cava syndrome (SVCS) in 50 %. There is no standard initial therapy regimen, anthracyclines with Rituximab are the most used. Local consolidation radiotherapy (RT) is reserved for bulky disease and to complete partial remissions (PR) after chemotherapy. AIMS: To analyze prognostic and epidemiological factors, treatment administered and response and survival rates of patients diagnosed with PMBCL in our center. METHODS: Retrospective cohort study between September 2003 and June 2014. The treatment received was 6 to 8 cycles of CHOP-like chemotherapy (Cyclophosphamide, Adriamycin, Vincristine, Prednisone ± methotrexate / Intrathecal triple therapy MTX- TIT ), with or without Rituximab, and subsequent radiotherapy if necessary. The following results were evaluated by univariate analysis: overall survival (OS), disease-free survival (DFS) and incidence of relapse after diagnosis. DFS was defined as the interval of time from complete remission (CR) to relapse or last visit. Response to treatment was assessed by PET-CT. RESULTS: We observed 14 patients diagnosed with PMBCL in our hospital with a median age of 33 years (r, 21-58 years) and female predominance (Š:‰ 10:4). At diagnosis 42.8 % had B symptoms and 42.8% elevated lactic dehydrogenase. Fifty percent of patients presented with SVCS. Central nervous system and bone marrow infiltration was not observed. Early-stage disease at diagnosis (I 30% and II 53%) was observed in 83%, with IPI 1 in 78.5% of patients. The number of cycles received was 6 in 78.5 %, 8 cycles in 14.2 %, and only 1 cycle of CHOP in one patient. Altogether 71.4 % received Rituximab and 71.4 % received MTX-TIT. Ten patients (71.4%) received RT (median 36 Gy) after chemotherapy, 9 of which had initial bulky disease. We observed an overall response rate of 92.8 % after chemotherapy (57.1 % CR, 35.7% PR). After a median follow-up of 60 months (r, 4.4 to 130.8 months) 12 patients had responded to treatment, were alive, without relapse and in complete response, and one patient is currently receiving the 6º cycle of CHOP pending reevaluation (awaiting last MTX-TIT and RT consolidation) and obtained CR after the third cycle of R-CHOP-MTX-TIT. Median overall survival was not reached and median DFS was of 54.8 months. Only one patient died (mortality 7.1 %) due to influenza A in the context of postchemotherapy aplasia after the first cycle of CHOP. CONCLUSIONS: We observed prognostic and epidemiological factors similar to those described in literature, although in our series, CHOP -like chemotherapy ( ± MTX- TIT ) with or without Rituximab and RT has shown improved survival rates and 100% of CR. Consolidation radiotherapy was successfully used to complete treatment in patients that only achieved PR after chemotherapy. Rescue chemotherapy followed by autologous hematopoietic cell transplantation was not required. It is difficult to draw conclusions on the impact of the therapeutic regimen received, we believe multicenter analysis with larger numbers of patients are necessary. Disclosures No relevant conflicts of interest to declare.

scholarly journals MYC Associated and Double Protein Lymphoma: Subset Analysis of SWOG S9704

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1710-1710 ◽  
Author(s):  
Soham D. Puvvada ◽  
Patrick J Stiff ◽  
Michael Leblanc ◽  
James R. Cook ◽  
Brad Kahl ◽  
...  
Keyword(s):  
B Cell ◽  
Clin Oncol ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Cell Transplant ◽  
Bulky Disease ◽  
Subset Analysis ◽  
Intent To Treat

Abstract Background: Outside of Burkitt lymphoma (BL), MYC rearrangements confer negative prognostic significance, particularly when co-associated with BCL2 rearrangements. While “double hit lymphomas (DHL)”, occurring in 5-10% of diffuse large B cell lymphoma (DLBCL) patients (pts), have known inferior outcomes with R-CHOP (Savage Blood 2009; Barrans J Clin Oncol 2010), emerging reports suggest that “double protein lymphomas (DPL)” with immunohistochemical (IHC) overexpression of MYC and BCL2 also fare poorly with standard therapy. The frequency of DPL is reportedly higher than DHL and may account for 20-30% of DLBCL cases (Johnson J Clin Oncol 2012; Hu Blood 2013). The optimal management strategy for DHL and DPL is undefined, and there is limited data on the potential role of consolidative transplant. SWOG S9704 was a phase III randomized study of aggressive NHL treated with CHOP +/-R for 5 cycles and then either 3 additional cycles of CHOP +/-R for autologous stem cell transplant (ASCT) in first remission (Stiff N Engl J Med 2013), which gives a unique opportunity to evaluate DPL outcomes in a prospective dataset. Methods: Among 370 eligible pts, 260 had DLBCL or B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL (BCLU); cases underwent morphologic review, and IHC analysis for MYC protein (>40% positive cells) was performed in 198 cases. BCL2 IHC (>30% positive cells), cell of origin (COO) classification (GC vs non-GC per Hans algorithm), and FISH studies for MYC were performed in all MYC IHC positive (+) cases with sufficient tissue. BCL2 FISH was also performed in cases positive for a MYC translocation via FISH. Clinical annotations were obtained through SWOG statistical center, and review of S9704 database. Results: There were 27 pts with MYC IHC+ among 198 available samples (13.6%), 19 of whom had concurrent BCL2 IHC+. Three of 6 evaluated pts had DHL via FISH (DHL group), and all were also DPL via IHC; thus, 16 pts had DPL without DHL. 8 patients with MYC IHC + had neither BCL2 positivity via FISH nor IHC (non-DHL, non-DPL group). For the 16 DPL pts (excluding 3 DHL pts), median (med) age was 59.9 y (range, 45-65y), 10 were male, 6 had bulky disease, all had elevated LDH (including 11 with LDH >2X ULN), and med AA IPI was 2. Among 11 evaluated pts for COO, 5 had GC whereas 6 had non-GC DLBCL phenotypes. All 3 DHL pts were female, and all had GC phenotype via Hans criteria. Among non-DHL/non-DPL pts (n=8), med age was 54.5y (range, 49-65y), 5 were male, 3 had bulky disease and all had elevated LDH. In terms of treatment, only 12 of 16 DPL pts were randomized (5 HCT, 7 no HCT), all 3 DHL pts were randomized (2 HCT) and 4 of 8 non-DHL/non-DPL pts were randomized. Reasons for non-randomization (n=8) were progression, lack of response or death. The med f/u for the entire cohort of 27 MYC IHC+ pts is 127 m (range, 94-147m); 21 pts have died (17 no HCT; 4 HCT groups). Med PFS for no HCT vs. HCT for all 27 MYC IHC + pts is 9m (95% CI: 5.0, 13.9) vs. not reached and 2-yr PFS is 16% (95% CI: 3.9%, 34.9%) vs. 63% (95% CI: 22.9%, 86.1%), respectively (Figure 1, intent-to-treat; Figure 2, randomized pts only). For the 16 DPL pts, 9 pts in the no HCT and 3 pts in the HCT group have progressed or died; med PFS for no HCT vs. HCT is 11m (95% CI: 6.7, 18.1) vs. 41m (95% CI: 7.1, NR), respectively, and 2-yr PFS is no HCT vs. HCT is 18% (95% CI: 2.9%, 44.2%) vs. 60% (95% CI: 12.6%, 88.2%), respectively Among 12 DPL pts actually randomized, 2-yr PFS was 29% for no HCT and 60% for HCT, but confidence intervals overlap substantially. All 3 DHL pts have progressed and died at a med of 6.5m. Conclusions: This is a subset analysis of the prospective S9704 trial; one of the largest data sets to address the question of upfront ASCT. True DHL were rare even in this high-risk cohort and had a dismal prognosis. The incidence of DPL was also less than reported in other series, and may reflect that adverse biologic features are more common in non-transplant, and thus older, populations. In an intent–to-treat analysis, there is a trend that MYC IHC+ and DPL patients consolidated with ASCT have improved outcomes; however, nearly one-third of MYC IHC+ pts were unable to be randomized due to early progression or death, suggesting that better induction regimens are needed. While these data are limited by small numbers, there seems to be a role for upfront ASCT in DPL which should be further explored. Support: CA32102, CA38926, CA21115 and in part by Bristol-Myers Squibb. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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