The Value of Molecular Monitoring for Residual Disease (MRD) in Early Morphological Remitters among Adults Diagnosed with B Cell ALL and Treated According to the MRC UKALL12 Protocol.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1467-1467 ◽  
Author(s):  
Letizia Foroni ◽  
Wayne Mitchell ◽  
Lena J. Rai ◽  
Sue Richards ◽  
Adele Fielding ◽  
...  
Keyword(s):  
B Cell ◽  
Residual Disease ◽  
Phase 1 ◽  
Induction Phase ◽  
Clinical Relapse ◽  
Cell Transplant ◽  
Molecular Monitoring ◽  
Free Survival ◽  
Post Induction ◽  
Time Point

Abstract Molecular monitoring of minimal residual disease (MRD) has become an independent and prognostically significant parameter in assessing outcome in adult and childhood acute lymphoblastic leukaemia (ALL). The aim of our study was to evaluate the impact of MRD in a standard risk group of adult B cell ALL patients who had achieved morphological remission following induction phase 1 therapy as part of the MRC UKALL12 protocol. Patients and Methodology. MRD tests were evaluated in fourty-seven patients with adult B cell ALL. They were negative for the t(9;22) or t(4;11) translocation and had received chemotherapy based treatment or auto stem cell transplant (A-SCT) only. Median age was 23 yrs (range 15.5–54.6 yrs); median WBC was 9.6 (range 1.1–163×109/l) with a predominance of common (28 pts) and pre B ALL (12 pts). All patients had at least one molecular marker which was tested by quantitative or semi-quantitative PCR with sensitivity ≥1E4. End points were either clinical relapse or disease free survival in complete remission with follow up ≥12 months. Time point for molecular evaluation were post induction phase 1, TP1 (median 0.9 mo; range: 0.6–1.8 mo) and post induction phase 2 (median 2.79 mo; range 1.8–3.5 mo). Results. Thirty three pts were tested at TP1 following morphological remission. Relapse free survival (RFS) analysis showed a statistically significant association between MRD positive tests (in 16 pts) and relapse, and MRD negative tests (in 17 pts) and CCR (p=0.03) (Figure 1, left diagram). Twenty five pts were analysed at TP2 following their early morphological remission. At this time point we observed the strongest association between MRD negative tests (in 13 pts) and CCR (in 10 pts) and MRD positive (12 pts) and relapse (in 11 pts) (p=0.01)(Figure 1, right diagram). Conclusions. Molecular monitoring of MRD shows that even among early morphological remitters a group of MRD positive patients can be identified that have poor overall outcome and may benefit from tailored therapies. Molecular assessment of residual disease should be used to stratify treatment in future adult ALL trials. Figure Figure

Molecular Monitoring of Residual Disease (MRD) during Induction and Intensification Phases in Low Risk Adult B Cell ALL Treated According to the MRC UKALL12 Protocol.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1466-1466 ◽  
Author(s):  
Letizia Foroni ◽  
Wayne Mitchell ◽  
Lena J. Rai ◽  
Anouska Casanova ◽  
Gareth Gerrard ◽  
...  
Keyword(s):  
B Cell ◽  
Residual Disease ◽  
Induction Phase ◽  
Molecular Monitoring ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Significant Parameter ◽  
Standard Risk ◽  
Time Point

Abstract Introduction and aims. Molecular monitoring of minimal residual disease (MRD) using Immunoglobulin (IG) and T cell receptor (TCR) targets has provided an independent and prognostically significant parameter of outcome in adult and childhood acute lymphoblastic leukaemia (ALL). The aim of our study was to evaluate the impact of molecular tests carried out during the first 20 to 24 weeks of chemotherapy for MRD in a standard risk group of adult B cell ALL patients. Patients and Methodology. We evaluated MRD tests in 63 patients with B cell ALL (37M/26F). Median age of our cohort was 24 yrs (range: 15.5–54.6 yrs) while median WBC was 9.9 (range: 1.1–553 × 109l). All were negative for the t(9;22) or t(4;11) translocation and received standard induction chemotherapy or auto stem cell transplant (A-SCT) only. All patients had at least one molecular marker which was tested by quantitative or semi-quantitative PCR with sensitivity ≥1E4 and all tests were carried out at time of morphological remission. End-points were relapse or continuous clinical remission (CCR) with follow up ≥12 months. Time point for molecular evaluation were post induction phase 1, TP1 (up to 1.8 mo), post induction phase 2 (1.8–3.5 mo), post intensification (3.5–5.7 mo). Median follow up was 92 months for patients in CCR (range 12–141 mo) and 15.5 months for patients who relapsed (range: 2.4–49 mo). Results. Thirty-five patients in complete morphological remission were tested at TP1. Relapse free survival (RFS) tests showed a statistically significant correlation (p=0.02) between MRD positive tests and relapse (n=19 pts) and MRD negative tests (n=16 pts) and relapse free survival. In addition, pts with resistant disease at TP1 (n=10; not included above) and MRD positive pts were indistinguishable as far as relapse FS and both faired extremely poorly (Figure A). Thirty patients were analysed at TP2. RFS confirmed the significant association between MRD positivity and poor outcome (n=16 pts) and MRD negativity and CCR (n=14 pts) (p=0.03) (Figure B). MRD data were also available for 43 patients at TP3. Association of MRD positive tests (n=15 pts) and MRD negative tests (n=28 pts) with poor and good outcome, respectively (p=0.0006) (Figure C) was strongest at this time point. Outcome correlated with level of MRD at all time points, with poorer outcome in patients with MRD >1E3. Conclusions. Molecular monitoring during induction and intensification for standard risk B cell ALL patients treated with UKALL12 protocol provides a prognostically significant parameter for the management of adult ALL in otherwise morphological remission and may in the future be used for patients’ stratification. Figure Figure

Value of Molecular Monitoring for Minimal Residual Disease Preceding Autologous SCT Following Diagnosis of B Cell Acute Lymphoblastic Leukemia in Patients Treated with the MRC UKALL12 Protocol.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1468-1468
Author(s):  
Letizia Foroni ◽  
Wayne Mitchell ◽  
Lena J. Rai ◽  
Anouska Casanova ◽  
Bella Patel ◽  
...  
Keyword(s):  
B Cell ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Clinical Relapse ◽  
Cell Transplant ◽  
Molecular Monitoring ◽  
Median Period ◽  
Time Of Harvest ◽  
Minimal Residual

Abstract Introduction and aims. Molecular monitoring of minimal residual disease has provided an independent and prognostically significant parameter in evaluating outcome in adult and childhood acute lymphoblastic leukaemia (ALL). The aim of our study was to assess the impact of MRD measured in bone marrow samples collected at time of harvest or prior to harvest in adult B cell receiving autologous stem cell transplant and correlate MRD with overall clinical outcome. Patients and Methodology. Patients were selected as de novo adult ALL of B cells. All patients were negative for the t(9;22) or (4;11) and had received chemotherapy followed by an autologous SCT (A-SCT). All patients had at least one molecular marker which was tested by quantitative or semi-quantitative PCR with sensitivity ≥1E4. End points were either clinical relapse or CCR with follow up ≥12 months except for two patients who died in CR following transplant, due to infections. Time point for molecular evaluation was a test preceding A-SCT or harvested BM. Nineteen patients were evaluable prior to/or at time of harvest. Nine were females and nine were males. Median age was 25.2 yrs (range: 15.2–52 yrs), total WCC was 7.1 (range: 2.3–68.9×109/l) at time of diagnosis with common ALL (14 pts) as the predominant phenotype. Patients received an A-SCT at a median period of 6 months from diagnosis (range: 5–18 months). Eight patients relapsed (median period to relapse: 22 mo; range: 8–35 mo) and 8 were in continuous clinical remission (CCR) (median follow up 33 mo; range: 8–139 mo). Median interval between Auto-SCT and relapse was 13.7 mo (range: 3–29 mo). Results. In seven patients residual disease was demonstrated in the BM prior to A-SCT and 6 of them relapsed. In 12 patients no residual disease was detected at time of harvest or prior to transplant and 10 are at present in CCR. The association between MRD positivity and relapse and MRD negativity and CCR was statistically significant in this cohort of patients (p=0.002)(Figure 1). Conclusions. Molecular monitoring of MRD can provide a useful tool for the monitoring of residual disease in BM harvest prior to SCT and correlates with outcome. It is therefore important that all BM harvests are tested for residual disease in future clinical trial that may use MRD for patients’ stratification. MRD tests prior to Auto-SCT and relapse FS MRD tests prior to Auto-SCT and relapse FS

Lenalidomide plus R-GDP (R2-GDP) in relapsed/refractory diffuse large B-cell lymphoma: Final results of the R2-GDP-GOTEL trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8019-8019 ◽  
Author(s):  
Luis de la Cruz Merino ◽  
Alejandro Martin ◽  
Esteban Nogales Fernández ◽  
Fernando Carnicero González ◽  
Eduardo Ríos Herranz ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Disease Free Survival ◽  
B Cell Lymphoma ◽  
Induction Phase ◽  
Cell Transplant ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Immune Biomarkers ◽  
Large B Cell

8019 Background: Lenalidomide is an immunomodulatory drug that could reverse rituximab refractoriness in lymphoma patients (pts). We conducted an open label multicenter phase 2 trial testing the efficacy and toxicity of a combination of lenalidomide and rituximab (R2) plus GDP schedule (R2-GDP) in Relapsed/Refractory Diffuse Large B Cell Lymphoma (R/R DLBCL) pts, not suitable for autologous stem cell transplant (ASCT). Methods: Patients with R/R DLBCL previously treated with at least 1 prior line of immunochemotherapy including rituximab, and not candidates for ASCT, were eligible. After a run-in phase period, treatment consisted of an induction phase with lenalidomide (LEN) 10 mg po d1-14, rituximab 375 mg/m2 iv d1, cisplatin 60 mg/m2 iv d1, gemcitabine 750 mg/m2 iv d1 and d8 and dexamethasone 20 mg d1-3, up to a maximum of 6 cycles. Pts without disease progression (DP) entered into a maintenance phase with LEN 10 mg, or last LEN dose received in the induction phase, d1-21 in cycles every 28 days. Primary endpoint was overall response rate (ORR) by investigator assessment. Secondary endpoints included disease free survival (DFS), event free survival (EFS), overall survival (OS), safety and response by cell of origin (COO), type of DLBCL (double-triple hit) and other microenvironment and genomic biomarkers. Results: 79 pts were enrolled between April 2015 and September 2018. Median age was 70 years (range 23-86), 48,7% women. 78 pts were considered for efficacy and safety in the intention to treat (ITT) analysis. With a median follow-up of 13 months at the time of cut-off (November 2019), ORRwas 59.0%, with 32.1% complete responses (CR) and 26.9% partial responses (PR). In the primary refractory population (n = 33), ORR was 45.5%, with 21.2% CR and 24.3% PR. There were no statistically significant differences in ORR with respect to COO. In Double-Hit R/R DLBCL (n = 16), ORR was 37.5% with 25% CR. Median OS was 12.0 months (6.9-17.0). Most common grade 3/4 (G3/4) adverse events were thrombocytopenia (60.2%), neutropenia (60.2%) and anemia (26.9%). Febrile neutropenia occurred in 14.1% pts. Most frequent non-hematologic G3/4 events were asthenia (19.2%), infection (15.3%) and renal insufficiency (6.4%). There were 4 toxic deaths related to the R2-GDP schedule. Conclusions: LEN with Rituximab and GDP (R2-GDP) is feasible and active in R/R DLBCL. Results in the primary refractory DLBCL population are particularly promising. Analysis of COO did not revealed differences in response rates. Immune biomarkers results will be showed at the meeting. Clinical trial information: EudraCT 2014-001620-29 .

scholarly journals Blinatumomab In pediatric relapsed/refractory B-cell acute lymphoblastic leukemia: RIALTO expanded access study final analysis

2022 ◽  
Author(s):  
Franco Locatelli ◽  
Gerhard Zugmaier ◽  
Noemi Mergen ◽  
Peter Bader ◽  
Sima Jeha ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Adverse Events ◽  
B Cell ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Cell Transplant ◽  
Open Label ◽  
Hematopoietic Stem ◽  
Expanded Access ◽  
Molecular Abnormalities

The safety and efficacy of blinatumomab, a CD3/CD19-directed bispecific T-cell engager molecule, for treatment of pediatric relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL) were examined in an open-label, single-arm, expanded access study (RIALTO). Children (>28 days, <18 years) with CD19+ R/R B-ALL received up to five cycles of blinatumomab by continuous infusion (cycle: 4 weeks on/2 weeks off). The primary endpoint was incidence of adverse events. Secondary endpoints included complete response (CR) and measurable residual disease (MRD) response within the first two cycles, relapse-free survival (RFS), overall survival (OS) and allogeneic hematopoietic stem cell transplant (alloHSCT) after treatment. At final data cutoff (1/10/20), 110 patients were enrolled (median age, 8.5 years; 88% ≥5% blasts at baseline). Blinatumomab treatment resulted in a low incidence of grade 3-4 cytokine release syndrome (n=2 [1.8%]) and neurologic events (n=4 [3.6%]). No blinatumomab-related fatal adverse events were reported. The probability of response was not affected by the presence of cytogenetic/molecular abnormalities. Median OS was 14.6 months (95%CI: 11.0─not estimable) and was significantly greater for MRD responders versus MRD non-responders (not estimable vs 9.3; HR 0.18, 95%CI: 0.08─0.39). One-year OS probability was higher for patients who received alloHSCT versus without alloHSCT post-blinatumomab (87% versus 29%). Median RFS for MRD responders (n=57) was 8.0 months (95%CI:3.4─10.1) versus 2.8 months (95%CI: 0.3─9.2) for MRD non-responders (n=10). Of patients achieving CR after 2 cycles, 73.5% (95%CI: 61.4%-83.5%) proceeded to alloHSCT. These findings support the use of blinatumomab as a safe and efficacious treatment for pediatric R/R B-ALL. (ClinicalTrials.gov identifier NCT02187354)

scholarly journals Bispecific T-cell engaging antibodies in B-cell precursor acute lymphoblastic leukemias: focus on blinatumomab

2020 ◽  
Vol 11 ◽  
pp. 204062072091963
Author(s):  
Jose-Maria Ribera ◽  
Eulalia Genescà ◽  
Jordi Ribera
Keyword(s):  
T Cell ◽  
B Cell ◽  
De Novo ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Development Program ◽  
Cell Transplant ◽  
Cell Precursor ◽  
Hematopoietic Stem ◽  
Clinical Development Program

Bispecific T-cell engaging antibodies are constructs engineered to bind to two different antigens, one to a tumor-specific target and the other to CD3-positive T cells or natural killer (NK) cells. Blinatumomab engages CD19 and CD3, performing effective serial lysis. The clinical development program in acute lymphoblastic leukemia (ALL) includes clinical trials in relapsed or refractory (R/R) patients and in B-cell precursor (BCP) ALL patients with measurable residual disease. Several trials are currently being conducted in de novo BCP-ALL, either in induction, consolidation, or before or after hematopoietic stem cell transplant. Combination with other targeted therapies or with other immunotherapeutic approaches are also underway. Several strategies are aimed to optimize the use of blinatumomab either by overcoming the mechanisms of resistance (e.g. inhibition of PD-1/PD-L1) or by improvements in the route of application, among others.

Chemoimmunotherapy with a Modified Hyper-CVAD and Rituximab Regimen Improves Outcome for Patients with De Novo Philadelphia Negative Precursor B-Cell Acute Lymphoblastic Leukemia (ALL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 836-836
Author(s):  
Deborah A. Thomas ◽  
Hagop M. Kantarjian ◽  
Stefan Faderl ◽  
William G. Wierda ◽  
Jorge Cortes ◽  
...  
Keyword(s):  
B Cell ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
High Dose ◽  
Induction Phase ◽  
Liposomal Daunorubicin ◽  
Cd20 Expression

Abstract Abstract 836 The hyper-CVAD regimen is an effective frontline program for de novo adult ALL and LL [Kantarjian, JCO 18:547, 2000; Kantarjian, Cancer 101:2788, 2004, Thomas, Blood 104:1624, 2004]. Intensive chemotherapy with hyper-CVAD (fractionated cyclophosphamide, vincristine [VCR], doxorubicin, dexamethasone) alternates with high dose methotrexate (MTX) and cytarabine every 21 days for 8 courses, followed by maintenance therapy with POMP (6-mercaptopurine, MTX, VCR, prednisone). Historical CR rate was 92% with 3-year disease-free survival (DFS) rate of 38%. The regimen was modified in 1999. Induction chemotherapy was given in a protective environment owing to higher mortality in patients (pts) aged 60 years or older (17% vs 3%). Course 2 of liposomal daunorubicin and cytarabine was incorporated owing to reports suggesting benefit of early anthracycline intensification. Rituximab 375 mg/m2 (days 1 & 11 of hyper-CVAD, days 1 & 8 of methotrexate-cytarabine) was given if CD20 expression was 20% or greater due to its association with disease recurrence [Thomas, Blood 113:6330, 2009]. The maintenance phase was extended to 30 months with additional intensifications owing to late relapses after completion of POMP therapy. Newly diagnosed or primary refractory (1 course only) pts with ALL (n=204) or LL (n=27) were treated on the two sequential studies. Burkitt-type leukemia/lymphoma (BLL) and Philadelphia positive ALL were treated on alternative protocols. From May 2000 to December 2001, 69 pts were treated with modified hyper-CVAD with anthracycline intensification (9 induction-consolidation courses). Course 2 was then eliminated from the regimen (8 courses), with an additional 162 pts treated to date (pts age 30 years or less are now treated with augmented BFM). Median age was 43 yrs (range, 15–83). CD20 expression was noted in 49%. Overall CR rate of the evaluable group (n=225) was 93%; 7 pts achieved PR (LL with residual disease), five failed to respond, and 4 died during the induction phase. Three-yr CRD and OS rates were 70% and 62%, respectively after a median follow-up of 50 months (range, 2–106+). In the younger CD20 positive precursor B-cell ALL subset (n=99), rituximab improved outcome compared to historical experience with hyper-CVAD alone (n=127), with 3-yr CRD rates (75% vs 45%, p<.001) and OS rates (65% vs 38%, p<.001) approaching those of their CD20 negative counterparts. In contrast to the Burkitt experience, rituximab was not beneficial for the elderly subgroup (OS rates 28% vs 34%, p NS). Anthracycline intensification did not improve outcome. The addition of rituximab to the hyper-CVAD regimen appears to benefit the younger pts (age less than 60 yrs) with CD20 positive precursor B-cell ALL. Incorporation of rituximab and other monoclonal antibodies (e.g., ofatumumab, epratuzumab) into frontline chemotherapy regimens for ALL should be investigated systematically. Disclosures: No relevant conflicts of interest to declare.

In the Era of Bortezomib-Based Chemotherapy the Presence of Minimal Residual Disease Predicts Progression Free Survival after Autologous Hematopoietic Cell Transplant

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5493-5493
Author(s):  
Robert F Cornell ◽  
Jade E Jones ◽  
Claudio A. Mosse ◽  
Heidi Chen ◽  
Laura Dugger ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Research Funding ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Free Survival ◽  
Kaplan Meier ◽  
Minimal Residual

Abstract Background: Retrospective studies have shown that achieving minimal residual disease (MRD) by multi-parameter flow cytometry (MFC) is predictive of outcomes in multiple myeloma (MM). Modern induction therapies including bortezomib (V), lenalidomide (R) followed by autologous hematopoietic cell transplant (AHCT) have resulted in substantial improvements in progression free survival (PFS) and overall survival (OS). The impact of bortezomib-based therapy on end of induction chemotherapy MRD status and post-AHCT MRD status is not well defined. We designed a prospective clinical trial (NCT01215344) to study the incidence of MRD negativity at end of induction and following AHCT, and its association with PFS and OS. Patients and Methods: Twenty patients with newly diagnosed, symptomatic MM were enrolled. They received four cycles of VRd induction therapy followed by AHCT. Dose modifications of VRd were controlled during the clinical trial. MRD status by MFC was evaluated at the end of induction chemotherapy and at day 100 post-AHCT. The MFC cut-off to determine MRD negativity was defined as 10-4. Outcomes analyzed included MM disease status, PFS and OS. Results: Three cohorts of patients were identified; patients achieving MRD negative status at the end of induction (cohort 1, 50%), those achieving MRD negative status only after AHCT (cohort 2, 15%) and patients never achieving MRD negative status (cohort 3, 35%). All patients achieving MRD negative status at the end of induction remained MRD negative post-AHCT. There were no significant differences in median age, renal function, disease stage, cytogenetic risk and maintenance chemotherapy post-AHCT between cohorts. The table summarizes characteristics of these cohorts. Patients who never achieved MRD negative status after AHCT had significantly shorter PFS (cohort 3) compared with patients who achieved MRD negative status (cohorts 1 and 2, p=0.008) (figure). The median PFS for cohort 3 was 2.64 years and not yet reached for the other cohorts. There were no significant differences in OS. Median follow-up for survivors was 2.53 years (range, 0.73-4.04). Conclusions: In this study, bortezomib-based therapy resulted in half of patients achieving MRD negative status with induction chemotherapy alone. AHCT improved the depth of response with 30% of patients who were MRD positive after induction therapy converting to MRD negativity following AHCT. Achieving a negative MRD state, pre- and at D100 post-AHCT resulted in improved PFS. These findings were independent of molecular cytogenetics or ISS stage. MRD positive status at day 100 post-AHCT is highly predictive of earlier disease progression, and may help identify patients for alternative management approaches. Delay of AHCT may be considered as a potential management option for patients with MRD negative status at the end of induction therapy, as being studied in the IFM DFCI study (NCT01208662). As some patients with MRD positive disease at the end of induction therapy become MRD negative with AHCT, these patients may benefit from AHCT and this population warrants further investigation. Table. Descriptive analysis Cohort 1 MRD -/- (%) (n=10) Cohort 2 MRD +/- (%) (n=3) Cohort 3 MRD +/+ (%) (n=7) Test Statistic Median Age 55 54 60 0.31 ISS Stage III 40 33 14 0.52 DS Stage III 89 67 60 0.14 Median Serum creatinine 0.90 0.60 0.88 0.10 Serum M-spike 2.0 1.9 2.1 0.80 Bone marrow plasma cells 14 44 14 0.18 Cytogenetics 0.37 Standard risk 40 0 57 Intermediate risk 50 67 43 High risk 10 33 0 Figure 1. Kaplan-Meier curve of progression-free survival comparing patients achieving MRD negative disease with MRD positive disease. Figure 1. Kaplan-Meier curve of progression-free survival comparing patients achieving MRD negative disease with MRD positive disease. Disclosures Cornell: Prothena: Research Funding. Jagasia:Takeda Inc: Research Funding.

Phase 1 study to evaluate the safety and efficacy of immunotherapy with tremelimumab and durvalumab in multiple myeloma patients receiving high dose chemotherapy and autologous stem cell transplant (HDT/ASCT) + peripheral blood lymphocyte (PBL) reinfusion.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS8051-TPS8051 ◽  
Author(s):  
Alexander M. Lesokhin ◽  
David J. Chung ◽  
Hearn J. Cho ◽  
Lisa Shohara ◽  
Paul Schwarzenberger ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibody ◽  
Overall Survival ◽  
Residual Disease ◽  
Hematologic Malignancy ◽  
Phase 1 ◽  
Objective Response ◽  
High Dose ◽  
Cell Transplant ◽  
Synergistic Activity

TPS8051 Background: Multiple myeloma (MM) remains an incurable hematologic malignancy despite the advent of new classes of drugs, including immunomodulatory agents, proteasome inhibitors, and monoclonal antibodies. The success and synergistic activity of immunotherapy (IMT) in solid tumors and hematologic malignancies has fueled their investigation in MM. HDT/ASCT as consolidation or as treatment for relapse remains a cornerstone for improving overall survival. HDT/ASCT transiently eliminates immune-suppressive cell populations and provides a viable IMT platform. Reinfusion of PBLs harvested pre-HDT induces immune responses, supporting its inclusion in IMT combinations. This study evaluates the effect of IMT, using tremelimumab (T), an anti-CTLA-4 monoclonal antibody, and durvalumab (D), an anti-PD-L1 monoclonal antibody, together with autologous PBL reinfusion and starting T ± D at Day 100 and earlier (Day 30) post-ASCT. Methods: This ongoing Phase 1, open-label, multicenter study (NCT02716805) evaluates the safety and preliminary efficacy of T and D administered on 2 schedules in MM patients at high risk for relapse as outlined below. Cohort initiation requires dose-limiting toxicity in < 2/6 patients in the previous cohort. The primary endpoint is safety. Secondary endpoints are objective response rate per IMWG, minimal residual disease, progression free and overall survival, and 100-day ASCT-related mortality. Exploratory endpoints include immunological effects and immune response. Enrollment opened 18 Nov 2016. As of 31 Dec 2016, 1 patient is enrolled in Cohort 1; enrollment is ongoing. Clinical trial information: NCT02716805. [Table: see text]

scholarly journals Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study

Blood ◽  
2013 ◽  
Vol 122 (17) ◽  
pp. 2965-2973 ◽  
Author(s):  
Conrad Russell Y. Cruz ◽  
Kenneth P. Micklethwaite ◽  
Barbara Savoldo ◽  
Carlos A. Ramos ◽  
Sharon Lam ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
B Cell ◽  
Stem Cell Transplant ◽  
Phase 1 ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
B Cell Malignancies ◽  
Phase 1 Study ◽  
Key Points

Key Points Allogeneic CD19-CAR VSTs are well tolerated by patients with relapsed B-cell malignancies post-HSCT. At periods of CD19-CAR VST persistence, these cells demonstrate antitumor activity.

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