A Single-Centre Experience of Clinico-Pathological Features, Risk Factors and Treatment Outcome of Posttransplant Lymphoproliferative Disorders (PTLD) after Renal Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4421-4421
Author(s):  
Esben Sondergaard ◽  
Charlotte Strandhave ◽  
Robert S. Pedersen ◽  
Kaj A. Jorgensen ◽  
Knud Bendix ◽  
...  
Keyword(s):  
T Cell ◽  
Renal Transplant ◽  
B Cell ◽  
Graft Function ◽  
B Cell Lymphoma ◽  
Solid Organ ◽  
Renal Transplant Recipients ◽  
Early Lesions ◽  
Anti Cd20

Abstract Background: PTLD is a lymphoid proliferation that develops as a consequence of immunosuppression and represents monoclonal B-cell, or rarely T-cell proliferations, occurring in a setting of decreased T-cell immune surveillance. PTLD is a major complication after solid organ transplantation. The disease is often unpredictable and devastating of nature resulting in a high rate of morbidity and patient mortality. Methods: Between 1990 and 2005 872 renal transplantations in 793 patients were performed at Skejby University Hospital in Aarhus and 11 cases of PTLD were identified retrospectively. PTLD Patients were investigated according to transplantation procedure, patient characteristics, type of lymphoma, treatment and outcome. Results: 11 of 793 renal transplant recipients (1,4%) developed PTLD. Patients (7 male, 4 female) ranged from 19 to 73 years of age at the time of diagnosis (mean age: 42 years). 8 had a cadaveric renal transplant while 3 received a transplant from related donor. Lymphomas were classified as diffuse large B-cell lymphoma in 10 cases and as Burkitt lymphoma in 1 case. No cases were of T-cell origin or Hodgkins lymphomas. Six cases were EBV positive (54%). Out of 11 cases, 5 were diagnosed within 1 year after transplantation, among which 4 were EBV positive, whereas 6 had a latency period of more than 1 year, among which only 2 were EBV positive. The mean latency time between grafting and diagnosis of PTLD among the early lesions was 7 months and among late lesions 6 years and 2 months (ranging from 1 month to 10 years and 8 months). Sites involved in PTLD were renal graft in 2 cases (both early lesions), lungs in 1 case, bowel system in 4 cases, CNS in 1 case, isolated lymph nodes in 1 case, widespread disease in 1 case and uncertain location in 1 case. All patients were treated by tapering of the immunosuppressive regimen. Two were treated with additional surgery and 3 with chemotherapy - all 5 of them are alive and in complete remission. Among those 5 patients 3 have preserved graft function (60%) and 2 returned to dialysis. One patient was treated with anti-CD20 monoclonal antibody, 3 had both conventional chemotherapy and anti-CD20 immunotherapy and 2 did not receive additional treatment. All 6 were dead at the end of the study period. With a median follow-up period of 5 years and 2 months (ranging from 6 months to 11½ years) 5 patients of 11 PTLD cases (45%) were alive with no sign of lymphoma relapse. Conclusions: PTLD is a severe complication, usually running an aggressive course and the outcome remains poor. The incidence in our population-based regional study material is 1,4%. Overall survival after a median follow-up of 62 months was 45%, with 60% of survivors maintaining graft function.

P1685POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER (PTLD): SINGLE INSTITUTIONAL EXPERIENCE OF TWO DECADES

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Inês Coelho ◽  
Sofia Cerqueira ◽  
Catarina Romãozinho ◽  
Luís Rodrigues ◽  
Rita Leal ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Central Nervous System Involvement ◽  
B Cell Lymphoma ◽  
Early Investigation ◽  
Solid Organ ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Hematopoietic Stem ◽  
Significant Difference

Abstract Background and Aims Post-transplant lymphoproliferative disorders (PTLD) are a group of heterogeneous lymphoid proliferations in chronic immunosuppressed recipients of solid organ and hematopoietic stem cell transplantation. Due to rarity of this disease, retrospective studies from transplant centers have been the main source to provide knowledge and treatment guidelines, which are still in evolution. This study examined the clinical outcomes and identified the predictors of mortality in adult renal transplant recipients who developed PTLD. Method We have studied the incidence of PTLD in adult renal transplant recipients who were transplanted in our hospital from 1996 to 2019. Data was collected for demographics, transplant and immunosuppression history, EBV and CMV serostatus, diagnosis, treatment and outcomes of PTLD. We performed univariate and multivariate analysis to identify prognostic factors. PTLD was classified according to 2018 WHO lymphoma classification. Results Twenty-four patients (12 males and 12 females) were eligible for the analysis. Mean age at time of the transplant was 43.1 ± 16.9 years, with a time between grafting and PTLD of 66 months (IQR 36-98 months). Mean follow-up time was 87 months (IQR 61-117 months). 25% of patients received a living donor renal transplant. 12,5% of patients received induction therapy with thymoglobulin. Mean age at time of PTLD diagnosis was 48,8 ± 17,9 years. Five cases were from Epstein-Barr virus (EBV) mismatched (D+/R-) transplants and there was seroconversion at time of PTLD diagnosis. 25% of patients had central nervous system involvement. 19 patients have monomorphic PTLD and the most common histological diagnosis was diffuse large B cell lymphoma. We identified that age >30 years at time of the transplant was predictor of mortality (HR 33.01; 95% CI: 3.24-336.14; p=0.003). Surprisingly, presence of B symptoms at time of PTLD diagnosis confer a better prognosis (HR 0,143; 95% CI: 0,035-0,579; p=0.006). All cases were managed with reduction in immunosuppression and converted to everolimus. 8 patients were treated with rituximab and there was no significant difference in the survival of these patients. By the end of follow-up, 7 patients went into remission, 1 returned to chronic dialysis, and 16 patients died (15 of them due to the disease). Mean time between PTLD and death was 3 months (IQR 1-6 months). Conclusion PTLD is an infrequent disease with a poor prognosis in renal transplant patients. Some cases have a close relationship with EBV, but it can also develop in the absence of the classical risk factors. The factor affecting mortality in our population was age >30 years at time of the transplant. Presence of B symptoms at time of PTLD diagnosis seems to confer a better prognosis probably due to early investigation and diagnosis of the disease.

scholarly journals Higher CD19+CD25+ Bregs are independently associated with better graft function in renal transplant recipients

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Eman H. Ibrahim ◽  
Mostafa G. Aly ◽  
Gerhard Opelz ◽  
Christian Morath ◽  
Martin Zeier ◽  
...  
Keyword(s):  
Renal Transplant ◽  
B Cell ◽  
Graft Function ◽  
Cell Subset ◽  
Immunosuppressive Drugs ◽  
Renal Transplant Recipients ◽  
Healthy Controls ◽  
Transplant Recipients ◽  
Significant Positive Association ◽  
Ifn Γ

Abstract Background The Identification of B cell subsets with regulatory functions might open the way to new therapeutic strategies in the field of transplantation, which aim to reduce the dose of immunosuppressive drugs and prolong the graft survival. CD25 was proposed as a marker of a B-cell subset with an immunosuppressive action termed Bregs. The effect of CD19 + CD25 + Bregs on graft function in renal transplant recipients has not yet been elucidated. We investigated a potential impact of CD19 + CD25 + Bregs on renal graft function as well as a possible interaction of CD19 + CD25 + Bregs with peripheral Tregs in healthy controls, end-stage kidney disease patients (ESKD), and renal transplant recipients. Moreover, we aimed to investigate the association of CD19 + CD25 + Bregs with serum IL-10, TGF-ß1, and IFN-γ in the same study groups. Method Thirty-one healthy controls, ninety renal transplant recipients, and eighteen ESKD patients were enrolled. We evaluated the CD19 + CD25 + Bregs and Treg absolute counts. Next, we investigated CD19 + CD25 + Bregs as predictors of good graft function in multiple regression and ROC analyses. Finally, we evaluated the association between CD19 + CD25+ Bregs and serum IL-10, TGF-ß, and IFN-γ. Results ESKD patients and renal transplant recipients showed lower counts of CD19 + CD25+ Bregs compared to healthy controls (p < 0.001). Higher CD19 + CD25+ Breg counts were independently associated with a better GFR in renal transplant recipients (unstandardized B coefficient = 9, p = 0.02). In these patients, higher CD19 + CD25+ Bregs were independently associated with higher Treg counts (unstandardized B = 2.8, p = 0.004). In ROC analysis, cut-offs for CD19 + CD25 + Breg counts and serum TGF-ß1 of 0.12 cell/μl and 19,635.4 pg/ml, respectively, were shown to provide a good sensitivity and specificity in identifying GFR ≥ 30 ml/min (AUC = 0.67, sensitivity 77%, specificity 43%; AUC = 0.65, sensitivity 81%, specificity 50%, respectively). Finally, a significant positive association between CD19 + CD25+ Bregs and TGF-ß1 was shown in renal transplant recipients (r = 0.255, p = 0.015). Conclusions Our findings indicate that higher counts of CD19 + CD25+ Bregs are independently associated with better renal function and higher absolute Treg counts in renal transplant recipients.

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.

scholarly journals Systematic Literature Review of the Clinical Evidence in Relapsed/Refractory (R/R) Large B-Cell Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5821-5821
Author(s):  
David G. Maloney ◽  
Fei Fei Liu ◽  
Lisette Nientker ◽  
Cathelijne Alleman ◽  
Brian Hutton ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Large B Cell Lymphoma ◽  
Car T ◽  
Large B Cell

Introduction: Large B-cell lymphoma (LBCL) is the most common subtype of non-Hodgkin lymphoma. Frontline treatment is curative in ~60% of patients (pts); however, ~30% of pts relapse and ~10% are refractory to frontline treatment. Treatment options for pts with relapsed/refractory (R/R) disease, especially in the third-line or greater (3L+) setting, have been primarily salvage chemotherapies (CTs). Recently, 2 CAR T cell products, axicabtagene ciloleucel (Yescarta®) and tisagenlecleucel (Kymriah®), and the antibody-drug conjugate, polatuzumab vedotin (Polivy®), were approved in the 3L setting. A systematic literature review (SLR) of R/R LBCL was conducted to identify relevant evidence on clinical outcomes in LBCL pts, including these new therapies, within the second-line and greater (2L+) or 3L+ setting, and to define the unmet medical need. Methods: This SLR was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and European Union Health Technology Assessment requirements. The review identified randomized and nonrandomized/observational studies within R/R LBCL, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma grade 3B (FL3B), primary mediastinal large B-cell lymphoma (PMBCL), DLBCL transformed from indolent lymphomas, and R/R DLBCL with secondary central nervous system (SCNS) involvement. Sources were EMBASE, MEDLINE, The Cochrane Library, and clinical conferences (ASCO, ESMO, EHA, ASH, ICML, AACR, and EORTC) from Jan 2000 to Apr 2019. Results : Following screening of 8683 database records and additional sources, 103 publications covering 78 unique studies were identified. Studies identified were characterized by line of treatment and R/R LBCL subtype (Figure). OS, PFS, DOR, OR, and safety observed from the identified studies were described. Disease subtypes, pt eligibility criteria, and length of follow-up varied notably across studies. In the 3L+ population, 11 salvage CT and 2 CAR T cell therapy studies reported survival outcomes. With salvage CT, the reported ORR across studies ranged from 0% to 54%, while CR ranged from 5.6%-31%. Median OS (mOS) ranged between 3-9 months, with one outlying study reporting mOS at 20 months. Median PFS (mPFS) reported within the salvage CT studies ranged from 2-6 months. Among CAR T cell therapies, pts treated with axicabtagene ciloleucel (n=101) reported a CR rate of 58% and median DOR (mDOR) was 11.1 months after a median follow-up of 27.1 months. mPFS was 5.9 months and mOS was not reached. At a median follow-up of 19.3 months, pts treated with tisagenlecleucel (n=115) had a CR of 40% but the mDOR was not reached. mOS was 11.1 months for all infused patients. In the 2L+ transplant-eligible population (36 studies), pts who received high-dose CT + HSCT achieved mOS between 9 months to 5 years. In the transplant noneligible population, 16 studies reported mOS between 3-20 months. Studies involving mixed transplant-eligible and noneligible populations (30 studies) reported mOS of 1-17 months. A few studies with limited sample sizes were found to report outcomes in LBCL subtypes (eg, PMBCL, SCNS lymphoma, DLBCL transformed from non-FL indolent lymphoma, FL3B). In the 3L+ setting, 1 study reported that mOS was not reached after a median of 6.6 months. In the 2L+ setting, 4 studies reported mPFS and mOS outcomes ranging between 2-9 months and 10-16 months, respectively. Among studies assessing safety of salvage CTs in R/R LBCL, neutropenia, leukocytopenia, thrombocytopenia, and infections were the most commonly reported adverse events (AEs), with neutropenia being the most reported. Among the 3 studies reporting safety outcomes of CAR T cell therapy, data suggest that hematologic AEs (possibly related to lymphodepleting CT), cytokine release syndrome, and neurotoxicity are the most reported. Conclusions : Despite the availability of new therapies for 2L+ and 3L + LBCL, examination of the current evidence has shown that there exists a high unmet need for additional therapeutic options that provide favorable benefit/risk and durable response for these patients. Furthermore, limited data are available for the rarer subtypes of LBCL. Both findings represent important treatment gaps for R/R LBCL that must be addressed in future research geared toward improvement of the current treatment landscape. Disclosures Maloney: Juno Therapeutics: Honoraria, Patents & Royalties: patients pending , Research Funding; Celgene,Kite Pharma: Honoraria, Research Funding; BioLine RX, Gilead,Genentech,Novartis: Honoraria; A2 Biotherapeutics: Honoraria, Other: Stock options . Liu:Celgene Corporation: Employment. Nientker:Celgene Corporation: Consultancy; Pharmerit Cöoperatief U.A.: Employment. Alleman:Pharmerit Cöoperatief U.A.: Employment; Celgene Corporation: Consultancy. Garcia:Celgene: Employment, Equity Ownership.

Other Tumours in Primary Cutaneous Lymphomas.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4417-4417
Author(s):  
Serena Rupoli ◽  
G. Goteri ◽  
P. Picardi ◽  
S. Pulini ◽  
A. Tassetti ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Skin Carcinoma ◽  
B Cell Lymphomas ◽  
T Cell Lymphomas ◽  
Cutaneous Lymphomas ◽  
Other Neoplasms

Abstract Patients with primary cutaneous lymphomas (PCLs) are treated with multiple therapeutic regimens, which may increase the risk of subsequent solid and haematological neoplasms. The aim of our study was to assess the incidence of other malignancies in our series of PCLs. From March 1994 to January 2007, 272 patients with PCLs (179 M, 93 F, median age 65 yr, range 14–88) were referred to our center for staging, treatment and follow-up. The clinical charts were reviewed to detect the incidence of malignancies occurred before or after the diagnosis of PCL or concomitantly. The series was composed by 228 patients (150 M, 78 F, median age 66 yrs) with T-cell lymphomas (202 Mycosis Fungoides/MF, 10 Sézary Syndrome/SS, 9 CD30+ PCL, 7 non MF/non CD30+ T cell PCL); 43 patients (28 M, 15 F, median age 60 yrs) with B-cell lymphomas (25 Follicular/FL, 14 marginal/MZL, 3 Leg-type, 1 Lymphoblastic) and one patient with CD4+/CD56+ hematodermic neoplasm. Chemotherapy was administered to 48 patients. During follow-up 12 patients died for the disease and 24 for other causes. A second tumor was observed in 41 patients (15%): 6 of them experienced more than one neoplasms: overall we observed 48 malignancies, 38 solid and 10 haematological. The other neoplasms appeared similarly before (20) and after (21) the diagnosis of PCL; in 7 cases they were diagnosed simultaneously. Solid tumours (17 preceding, 4 concurrent, 17 subsequent) were diagnosed in: skin (11), colon (5), lung (4), breast (3), CNS (3), bladder (2), liver (2), kidney (2), uterus (2), testis (1), prostate (1), stomach (1), thyroid (1). The haematological malignancies (3 preceding, 3 concurrent, 4 subsequent) were: B-cell lymphomas (4), acute myeloid leukemias (3), plasmocytoma (1), T-cell lymphoma (1), Hodgkin’s lymphoma (1). Among the six patients with more than one adjunctive neoplasms one patient had lung and kidney carcinoma preceding PCL; two patients a preceding carcinoma (skin and bladder, respectively) and subsequently a lung carcinoma; other two patients showed both a preceding and a concurrent neoplasm (skin and colon carcinoma, B-cell lymphoma and skin carcinoma, respectively). Finally a patient had a preceding skin carcinoma, a concurrent nodal Hodgkin’s lymphoma and a subsequent nodal B-cell lymphoma. So we have reported 48 other neoplasms in 41 patients within 272 PCLs (15%). The occurrence of the other malignancy was not related to the B/T phenotype of PCLs, as it was observed in 35/228 (15.4%) T-cell lymphomas (32 MF, 2 SS, 1 non MF/non CD30+ T cell lymphoma) and in 6/43 (14%) B-cell lymphomas (3 FL, 3 MZL; χ2 test: P=0.88). The interval of occurrence was longer for tumors preceding (median 60 mo.s, range 8–180) than for tumors following PCL (median 45, range 6–122). The administration of chemotherapy for PCL was not associated with an increased incidence of second neoplasm(χ2 test, P=0.77). Multicentric studies might help in elucidating the role of genetic and immunitary factors in the pathogenesis of multiple neoplasms in patients with PCLs.

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.

Durable Remission in Recurrent T-Cell—Rich B-Cell Lymphoma with the Anti-CD20 Antibody Rituximab

2001 ◽  
Vol 2 (3) ◽  
pp. 185-187 ◽  
Author(s):  
Yasodha Natkunam ◽  
Thomas S. Stanton ◽  
Roger A. Warnke ◽  
Sandra J. Horning
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cd20 Antibody ◽  
Anti Cd20 ◽  
Durable Remission

Real-world outcomes of elderly patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) treated with chimeric antigen receptor T-cell (CAR-T) therapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8039-8039 ◽  
Author(s):  
Lindsey Fitzgerald ◽  
Adam Kittai ◽  
Loretta J. Nastoupil ◽  
Alexandra Waller ◽  
Caron A. Jacobson ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Hematopoietic Cell Transplantation ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
The Elderly ◽  
Tumor Characteristics ◽  
Car T ◽  
Baseline Characteristics

8039 Background: CAR-T has drastically improved outcomes for R/R DLBCL patients (pts). While CAR-T is now standard of care for the treatment of R/R DLBCL, little is known about its efficacy and toxicity in elderly pts. Methods: We conducted a multi-center retrospective analysis of pts age ≥ 70 years old with R/R DLBCL treated with either axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel). Pt demographics, tumor characteristics, CAR-T data, survival and toxicity outcomes were collected at the time of T cell infusion and follow up. Comorbidities were measured using the cumulative illness rating score (CIRS) and hematopoietic cell transplantation-specific comorbidity index (HCT-CI). Results: A total of 77 pts were analyzed with a median age of 73 (range, 70-88); 30 (39%) pts were age ≥75. Most pts received axi-cel (n = 61, 79%). Unfavorable tumor characteristics included 27 (35%) pts with activated B-cell subtype and 12 (16%) with double/triple hit lymphomas. Median CIRS was 8 (range 0-25) and median HCT-CI was 2 (range 0-9) with significantly higher median CIRS and HCT-CI in pts age ≥75. With a median time to follow up of 5.2 months (m), median progression free survival (PFS) was 12m and median overall survival (OS) was 15.5m. There was no difference in PFS when comparing younger pts (age 70-74) to older pts (age ≥ 75), but median OS was significantly shorter for older pts (7.8m vs. not reached; hazard ratio [HR] 0.46, CI 0.21-0.98; p = 0.04). In a multivariate analysis (MVA) of PFS adjusting for baseline characteristics, HCT-CI > 2 (HR 0.23, CI 0.07-0.77; p = 0.02) and use of axi-cel (HR 0.07, CI 0.02-0.32; p = < 0.001) were associated with worse PFS. Grade 3/4 (Lee criteria) cytokine release syndrome (CRS) and CAR-related encephalopathy syndrome (CRES) were assessed in MVA adjusting for baseline characteristics. CRS was associated with CIRS ≥6 (odds ratio [OR] 3.92, CI 1.07-14.3; p = 0.002) and use of axi-cel (OR 44.9, CI 8.20-245.6; p = 0.006). CRES was associated with older age (OR 6.10, CI 1.86-20.0; p = 0.003), CIRS ≥6 (OR 3.92, CI 1.07-14.3; p = 0.04) and use of axi-cel (OR 44.9, CI 8.2-245.6; p = < 0.0001). Conclusions: Pts age ≥75 treated with CAR-T had worse OS, but comparable PFS as compared to younger pts. Validated frailty measurements (CIRS) predicted for increased CRS and CRES. Use of axi-cel was associated with worse PFS and increased toxicities in the elderly, but propensity matched scoring analysis will need to confirm this. Additional pts and longer follow up are required to validate these results.

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