Long Term Follow-Up Of De Novo Or Minimally Treated Burkitt Lymphoma/Leukemia (BL/B-ALL) After Frontline Therapy Per The Hyper-CVAD Regimen With Or Without Rituximab: 20-Year Cumulative Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3917-3917 ◽  
Author(s):  
Preetesh Jain ◽  
Hagop M Kantarjian ◽  
Jorge E. Cortes ◽  
Elias J. Jabbour ◽  
Stefan H. Faderl ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Historical Experience ◽  
Frontline Therapy ◽  
Anti Cd20

Abstract Background Incorporation of the anti-CD20 monoclonal antibody rituximab into intensive, multi-agent chemotherapy regimens has been widely applied as frontline therapy of BL/B-ALL. We previously reported significant improvements in disease-free (DFS) and overall survival (OS) rates with the addition of rituximab to hyper-CVAD compared with the historical experience. We now report a cumulative update of the findings over a 20-year period. Methods 52 patients (pts) with newly diagnosed non-HIV BL (n=12) or B-ALL (n=40) were treated with hyper-CVAD and rituximab from February 2000 to June 2013. Chemoimmunotherapy was administered as previously described (Thomas DA et al, Cancer 2006:106; 1569-80). A separate cohort (n=9) with bcl-2 expression was excluded since they represented the category of B-cell lymphoma, unclassifiable, with intermediate features between diffuse large B-cell lymphoma and BL as per the 2008 revision of the WHO classification. Median age was 41 yrs (range, 17–77); 11 (21%) were aged 60 yrs or older. Six of the 52 pts were inevaluable for response: 3 were enrolled in complete remission (CR) after pretreatment with one cycle of chemotherapy and 3 had surgical resection of the tumor mass without evidence of residual disease. Seven (13%) had CNS involvement at presentation. Lactate dehydrogenase (LDH) level (ULN > 618 U/L) was elevated in 40 (77%). Outcome of the chemoimmunotherapy group was compared to historical experience with 44 pts treated with hyper-CVAD without rituximab from August 1992 to January 2000. Results All evaluable pts responded; 42 of 44 (95%) achieved CR and 2 achieved partial response. All 11 pts aged 60 yrs or older achieved CR. After a median follow up of 90 months, 10 (19%) pts relapsed with only one survivor (late relapse after 7 yrs successfully salvaged with DA-EPOCH-R). Twelve (29%) pts died in CR from infections (n=4), other malignancies (n=4), other preexisting comorbid medical conditions (n=2), or unknown causes (n=2). Overall 5-yr DFS and OS rates were 70% and 70% respectively, improved compared with corresponding historical cohort rates of 60% and 51%. Six pts developed secondary dyscrasias (1 with acute myelogenous leukemia [AML] at 7 yrs, 1 with t(8;21) AML at 3 yrs, 1 with monosomy 7 AML at 3 yrs, 3 with myelodysplastic syndrome (range 1-8 yrs). Toxicity profile was similar to hyper-CVAD alone. In the cohort (n=9) of bcl-2 positive dual hit lymphoma/leukemia (DHL) typically associated with poor prognosis, the 5-yr DFS and OS rates were 71% and 56% respectively; 4 were long-term survivors beyond 5 years without disease recurrence. Conclusions The incorporation of rituximab into the hyper-CVAD regimen has improved outcomes for de novo BL/B-ALL, with achievement of respectable cure rates. Bortezomib has been incorporated for the DHL subset in an effort to improve the results. Later generation anti-CD20 monoclonal antibodies such as ofatumumab have supplanted rituximab. Investigation of other novel monoclonal antibodies such as blinatumomab or inotuzumab for BL/B-ALL is clearly warranted. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Long-Term Follow-Up of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy

2020 ◽  
Vol 38 (32) ◽  
pp. 3805-3815
Author(s):  
Kathryn M. Cappell ◽  
Richard M. Sherry ◽  
James C. Yang ◽  
Stephanie L. Goff ◽  
Danielle A. Vanasse ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T

PURPOSE Anti-CD19 chimeric antigen receptors (CARs) are artificial fusion proteins that cause CD19-specific T-cell activation. Durability of remissions and incidence of long-term adverse events are critical factors determining the utility of anti-CD19 CAR T-cell therapy, but long-term follow-up of patients treated with anti-CD19 CAR T cells is limited. This work provides the longest follow-up of patients in remission after anti-CD19 CAR T-cell therapy. METHODS Between 2009 and 2015, we administered 46 CAR T-cell treatments to 43 patients (ClinicalTrials.gov identifier: NCT00924326 ). Patients had relapsed B-cell malignancies of the following types: diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma (DLBCL/PMBCL; n = 28), low-grade B-cell lymphoma (n = 8), or chronic lymphocytic leukemia (CLL; n = 7). This report focuses on long-term outcomes of these patients. The CAR used was FMC63-28Z; axicabtagene ciloleucel uses the same CAR. Cyclophosphamide plus fludarabine conditioning chemotherapy was administered before CAR T cells. RESULTS The percentages of CAR T-cell treatments resulting in a > 3-year duration of response (DOR) were 51% (95% CI, 35% to 67%) for all evaluable treatments, 48% (95% CI, 28% to 69%) for DLBCL/PMBCL, 63% (95% CI, 25% to 92%) for low-grade lymphoma, and 50% (95% CI, 16% to 84%) for CLL. The median event-free survival of all 45 evaluable treatments was 55 months. Long-term adverse effects were rare, except for B-cell depletion and hypogammaglobulinemia. Median peak blood CAR-positive cell levels were higher among patients with a DOR of > 3 years (98/µL; range, 9-1,217/µL) than among patients with a DOR of < 3 years (18/µL; range, 0-308/μL, P = .0051). CONCLUSION Complete remissions of a variety of B-cell malignancies lasting ≥ 3 years occurred after 51% of evaluable anti-CD19 CAR T-cell treatments. Remissions of up to 9 years are ongoing. Late adverse events were rare.

Long-Term Follow-Up of Reduced Intensity Transplantation with an Alemtuzumab-Containing Regimen for Aggressive Non-Hodgkins Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1661-1661
Author(s):  
Kirsty Thomson ◽  
Emma Morris ◽  
Adrian Bloor ◽  
Gordon Cook ◽  
Donald Milligan ◽  
...  
Keyword(s):  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Grade ◽  
Autologous Transplant ◽  
Donor Type ◽  
Unrelated Donors ◽  
Reduced Intensity

Abstract The outlook for patients with relapsed or refractory high-grade NHL failing autologous transplant is poor. Allogeneic transplant with myeloablative conditioning carries a high non-relapse mortality (NRM) in this setting, and reduced intensity conditioning is being investigated. We report 54 consecutive patients with a diagnosis of diffuse large B cell lymphoma (n=48;89%: presenting de novo [n=31] or following transformation from follicular lymphoma [FL, n=17]) or anaplastic large cell lymphoma (n=6;11%) who underwent reduced intensity allogeneic transplantation (RIC) at 8 centres. Conditioning was with fludarabine 150mg/m2, melphalan 140mg/m2 and alemtuzumab (20–100mg), and cyclosporin A was given at 3mg/kg. Donors were HLA-matched siblings in 34 (63%), and unrelated in 20 (37%), of whom 11 were HLA-mismatched at up to 3/10 loci. Median age was 44 yrs (18–64), median lines of prior therapy was 4 (1–7), 37 (69%) patients had previously undergone autologous transplantation, and 11 (20%) had chemorefractory disease at the time of RIC. Median follow-up from RIC was 49 months (8–87). NRM was 30% at 1 yr and 34% at 5 yrs, with 18/19 events occurring within the 1st 16 months. There was no significant association between NRM and donor type or prior autograft. Estimated relapse rate was 32% at 5 years for all patients: 25% in de novo high-grade NHL and 46% in those with transformed FL. Fifteen of the 16 relapses occurred within the 1st yr post-transplant, at a median of 3 months (1–42). Twelve patients received donor lymphocyte infusions (DLI) at a starting dose of 1–10 × 106 CD3+ cells/kg. Of the 12, 5 had primary DLBCL- 4 died within 5 months of DLI having had no response, and 1 had additional anti-tumor therapy pre-DLI and remitted. Of the 7 with transformed FL, 4 remitted, 2 with therapy prior to DLI and 1 with GVHD. Overall survival (OS) for the whole cohort was 45% at 5 yrs, with current progression-free survival (cPFS) of 46% at 5 yrs. There was no significant difference in OS or cPFS when analysed by donor type (5 yr OS 46% for sibling donors, 44% for unrelated donors;p=0.612), presence of prior autologous transplant (5 yr OS 43% for those having failed autograft, 51% for those who had not undergone autograft;p=0.614), or presence of de novo high-grade NHL (OS 39% at 5 yrs for those with de novo high-grade NHL, 58% for those with transformed FL;p=0.208). Both OS (p=0.003) and cPFS (p=0.002) were significantly impacted by the presence of chemorefractory disease pre-RIC, with both OS and cPFS 55% at 5 yrs for chemosensitive disease, and 9% at 5 yrs for chemorefractory. In conclusion, given the median follow-up of over 4 yrs and the aggressive nature of the disease in these patients, with extensive pre-treatment including a failed autologous transplant in the majority, these are encouraging results raising the prospect of long-term survival in a significant cohort. We propose that all patients with DLBCL relapsing following an autograft whose disease is sensitive to salvage chemotherapy should be strongly considered for RIT, using related or unrelated donors.

scholarly journals Long Term Follow up of SWOG S0313: Ibritumomab Tiuxetan Consolidation after 3 Cycles of CHOP Plus Radiotherapy for High Risk Limited Stage Aggressive B-Cell Lymphoma

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 ◽  
...  
Keyword(s):  
Risk Factor ◽  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Ibritumomab Tiuxetan ◽  
Large B Cell Lymphoma ◽  
Large B Cell

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.

Diffuse Large B-Cell Lymphoma (DLBCL) Patients with Composite Histology Have Improved Early Outcome Compared to De Novo DLBCL When Treated with R-CHOP

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2819-2819
Author(s):  
Matthew J. Maurer ◽  
Thomas E. Witzig ◽  
William R. Macon ◽  
Sergei I. Syrbu ◽  
James R. Cerhan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Follicular Lymphoma ◽  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Indolent Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: A significant percentage of DLBCL patients present with a composite histology, often seen as a node containing both follicular lymphoma and DLBCL or DLBCL in the node and discordant indolent lymphoma in the bone marrow. Literature from the pre-rituximab era suggests DLBCL patients with transformed lymphoma or composite histology have worse outcome than de novo DLBCL. Here we report on early events in a cohort of R-CHOP treated patients. Goal: To determine whether patients with composite lymphoma have an inferior event free survival (EFS) and overall survival (OS) compared to de novo diffuse large B-cell lymphoma when treated with R-CHOP. Methods: Newly diagnosed patients treated with an R-CHOP containing regimen were prospectively enrolled in our Lymphoma SPORE registry from 9/2002 through 6/2007. Pathology was centrally reviewed. All patients were followed for retreatment, disease progression, and death. Results: 401 DLBCL patients were enrolled; 14% (57/401) had a composite histology. 33 patients had DLBCL and another histology, predominantly follicular lymphoma (n=29), in the same node. 20 patients had a non-DLBCL histology in a distinct location from the DLBCL; this was primarily indolent lymphoma in the bone marrow (n=15). 4 patients had both. 19% (75/401) of patients died during follow-up and 30% (121/401) had an event (death due to any cause, progression, or retreatment). Median follow-up for living patients was 34 months (range, 5–73). Composite DLBCL patients had higher event-free (3 year EFS = 79%) and overall (3 year OS = 93%) survival then de novo DLBCL (3 year OS = 66%, 3 year EFS 79%), p=0.05 and p=0.005 respectively. These differences remained statistically significant after adjusting for the International Prognostic Index (IPI): EFS HR = 0.53, 95% CI: 0.29–0.97, p=0.02; OS HR=0.28, 95% CI: 0.10–0.76, p=0.002. OS and EFS for composite DLBCL more closely resembled R-CHOP treated grade III follicular lymphoma (A,B) from the same cohort (3 year EFS = 81%, 3 year OS = 93%). Improved outcome for composite DLBCL was consistent whether the additional histology was in the same node or distinct from the DLBCL. Conclusions: R-CHOP treated DLBCL patients with indolent discordant bone marrow involvement or other composite histology have improved early OS and EFS compared to de novo DLBCL. Further follow-up is needed to assess the long-term prognosis of composite DLBCL in the rituximab era. Histology N Age &gt; 60 Stage III/IV LDH &gt; ULN PS &gt; 1 &gt;2 EN Sites 3 YR EFS 3 YR OS * Denotes statistically significant difference at p=0.05 de novo DLBCL 344 58% 56% 56% 17% 22% 66% 78% Composite DLBCL 57 65% 77%* 34%* 18% 32% 79%* 93%* Figure Figure

Long-term follow-up of abbreviated R-CHOP chemoimmunotherapy for completely resected limited-stage diffuse large B cell lymphoma (CISL 12-09)

2020 ◽  
Vol 99 (12) ◽  
pp. 2831-2836
Author(s):  
Sora Kang ◽  
Hyungwoo Cho ◽  
Byeong Seok Sohn ◽  
Sung Yong Oh ◽  
Won-Sik Lee ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Limited Stage ◽  
Large B Cell Lymphoma ◽  
Long Term Follow Up ◽  
Large B Cell

Long-Term Results of the R-CHOP Study in the Treatment of Elderly Patients With Diffuse Large B-Cell Lymphoma: A Study by the Groupe d'Etude des Lymphomes de l'Adulte

2005 ◽  
Vol 23 (18) ◽  
pp. 4117-4126 ◽  
Author(s):  
P. Feugier ◽  
A. Van Hoof ◽  
C. Sebban ◽  
P. Solal-Celigny ◽  
R. Bouabdallah ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Long Term Results ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

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

scholarly journals B-cell Lymphoma in retrieved femoral heads: a long term follow up

2009 ◽  
Vol 10 (1) ◽  
Author(s):  
Eline W Zwitser ◽  
Arthur de Gast ◽  
Mirjam JA Basie ◽  
Folkert J van Kemenade ◽  
Barend J van Royen
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Femoral Heads ◽  
Long Term Follow Up
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