Duration of response to loncastuximab tesirine in relapsed/refractory diffuse large B-cell lymphoma by demographic and clinical characteristics: Subgroup analyses from LOTIS 2.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7546-7546
Author(s):  
Paolo Caimi ◽  
Weiyun Z. Ai ◽  
Juan Pablo Alderuccio ◽  
Kirit Ardeshna ◽  
Mehdi Hamadani ◽  
...  
Keyword(s):  
High Risk ◽  
Poor Prognosis ◽  
Clinical Characteristics ◽  
Cell Lymphoma ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
Phase 2 ◽  
Large B Cell Lymphoma ◽  
Subgroup Analyses ◽  
Duration Of Response

7546 Background: Outcomes for patients with refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL) are poor, particularly for those with high-risk clinical characteristics. There remains an unmet need for new treatment options for these patients. Loncastuximab tesirine (Lonca) is an antibody-drug conjugate comprising a humanized anti-CD19 antibody conjugated to a potent pyrrolobenzodiazepine dimer toxin. LOTIS 2 was a pivotal Phase 2 study that demonstrated substantial single-agent anti-cancer activity of Lonca in patients with R/R DLBCL. Efficacy and safety data were presented at ASH 2020 (Caimi et al, ASH 2020; abstract 1183). Here we present subgroup analyses of duration of response (DoR) to Lonca by demographic and clinical characteristics. Methods: Adult patients with R/R DLBCL who had received ≥2 prior therapies were enrolled in this Phase 2, multicenter, single-arm, open-label study of single-agent Lonca (150 µg/kg every 3 weeks for 2 doses, followed by 75 µg/kg thereafter for up to 1 year). The primary analysis has previously been reported, with a primary endpoint of overall response rate (ORR). Patients are being followed-up every 12 weeks for up to 3 years. DoR was a key secondary efficacy endpoint, defined as time from the first documentation of response (central review) to disease progression or death. We analyzed pre-specified demographic and clinical characteristic subgroups for DoR. Results: As of data cut-off (August 6, 2020), ORR in the total population (N = 145) was 48.3% (24.8% had complete response [CR] and 23.4% had partial response [PR]). Median DoR (mDoR) for the 70 responders was 12.58 months. mDoR for patients with CR and PR was 13.37 months and 5.68 months, respectively. Overall, subgroups with high-risk characteristics for poor prognosis had a DoR comparable to the whole study population. mDoR for patients with double-/triple-hit DLBCL was 13.37 months, with advanced stage disease was 12.58 months, and with transformed disease was 12.58 months. The mDoR for older patients was longer than for younger patients (≥75 years, 13.37 months; 65 to < 75 years, 12.58 months; < 65 years, 9.26 months). Patients with DLBCL refractory (defined as no response to therapy) to first-line, most recent line, and all prior lines of therapy had mDoRs of 9.63 months, 9.26 months, and 9.63 months, respectively. Conclusions: Durable responses were observed with the recommended Phase 2 dose regimen of Lonca in heavily pre-treated patients and those at high risk of poor prognosis, including older patients and those with double-/triple-hit, advanced stage, transformed, and primary refractory DLBCL. Updated DoR data will be presented at the meeting. Clinical trial information: NCT03589469.

scholarly journals Favourable outcomes for high-risk diffuse large B-cell lymphoma (IPI 3–5) treated with front-line R-CODOX-M/R-IVAC chemotherapy: results of a phase 2 UK NCRI trial

2020 ◽  
Vol 31 (9) ◽  
pp. 1251-1259 ◽  
Author(s):  
A.K. McMillan ◽  
E.H. Phillips ◽  
A.A. Kirkwood ◽  
S. Barrans ◽  
C. Burton ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Phase 2 ◽  
Front Line ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Role Of Interim,-PET In Poor Prognosis Young Patients With Diffuse Large B Cell Lymphoma At Diagnosis: Data From An Ancillary Study Of a Prospective Randomized Phase III Study (DLCL04) From the Fondazione Italiana Linfomi

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5088-5088
Author(s):  
Luigi Rigacci ◽  
Patrizia Pregno ◽  
Benedetta Puccini ◽  
Andrea Evangelista ◽  
Annalisa Chiappella ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Clinical Characteristics ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Ancillary Study ◽  
Interim Pet ◽  
Large B Cell Lymphoma ◽  
Dose Dense

Abstract Introduction The role of interim-PET (i-PET), after two cycles of chemotherapy, in advanced stage Hodgkin's lymphoma is well defined; the same role in diffuse large B cell lymphoma (DLBCL) is still controversial. The Fondazione Italiana Linfomi planned a prospective randomized phase III trial, addressed to young poor prognosis DLBCL patients at the diagnosis, with a 2x2 factorial design aimed at investigating the possible benefit of intensification with R-HDC+ASCT after R-dose-dense chemotherapy delivered at two different level of dose (R-CHOP14/R-MegaCHOP14). During this study an ancillary study was designed to define the prognostic impact of i-PET on progression free survival (PFS) after two cycles of immunochemotherapy in all treatments arms. Patients and methods As described by Vitolo et al (oral communication, abs 688 ASH 2012), patients were stratified according to aa-IPI and randomized at diagnosis to receive: R-CHOP14 x 8 cycles; R-MegaCHOP14 (1200 mg/sqm Cyclophosphamide, 70 mg/sqm Doxorubicin, standard dose Vincristine and Prednisone) x 6; R-CHOP14 x 4 + R-HDC (Rituximab + High Dose Cytarabine + Mitoxantrone + Dexamethasone) followed by BEAM and ASCT; R-MegaCHOP14 x 4 + R-HDC + BEAM and ASCT. G-CSF support was mandatory. Seventeen centers agreed to participate in the study and enrolled patients. All evaluable patients had performed basal PET and i-PET. A visual dichotomous criteria, according to Deauville Criteria (First Consensus Conference, 2009), was used to define the i-PET result. The final response was identified according to 2007 Cheson response criteria. Results From June 2005 to September 2010, 399 patients were randomized in the overall DLCL04 study and 130 were enrolled for the ancillary PET study , 69 in the R-HDC+ASCT and 61 in R dose dense therapy respectively. The clinical characteristics, as in the overall DLCL04 study, were well balanced among the four arms of therapy excluding a selection bias in the group of patients studied with i-PET. The i-PET result was positive in 74 patients and negative in 56 patients, no differences were observed between negative and positive i-PET results according to clinical characteristics and group of treatment. In particular, in R-dose dense arm 27 were negative and 34 positive, in R-HDC+ASCT 29 were negative and 40 positive, according to immunochemotherapy scheme in R-CHOP14 29 were negative and 40 were positive, in MegaCHOP14 27 were negative and 34 were positive. With a median follow-up of 36 months, 3-year PFS and 3-year Overall Survival (OS) rates for the whole series were: 64% (95% CI:59-69) and 79% (95% CI:74-83) respectively. No differences in PFS was reported according to i-PET result. In particular 3-year PFS were 87%(95% CI:75-94) in i-PET negative patients and 76% (95% CI: 65-85) in i-PET positive patients respectively (p: 0.09 The 3-year PFS according to I- PET results in the different treatment arm were: in the R-HDT+ASCT group i-PET negative or i-PET positive patients had a 3-year PFS of 83% (95% CI:63-92) and 79% (95% CI:63-89) respectively; in the R-dose dense i-PET negative or i-PET positive patients had a 3-year PFS of 92% (95% CI:73-98) and 72% (95% CI:54-85) with a p value near the significance (0.07). According to OS, i-PET negative and i-PET positive patients had a 3-year OS of 89%(95% CI:76-95) and 83%(95% CI:72-90) respectively, p=0.219. Conclusions In our multicenter prospective study, addressed to young poor prognosis DLBCL patients at the diagnosis, i-PET, performed after two immunochemotherapy cycles and analyzed with a visual method, is not able to identify two different risk population. To confirm our data, we are planning in the near future a centralized revision of all evaluable PET. In conclusion, our feeling is that the i-PET after two cycles in poor prognosis DLBCL patients is too early to predict a chemorefractory disease and more parameters must be considered to define clinical response in these patients. Disclosures: No relevant conflicts of interest to declare.

90Y-Ibtritumomab as a Single Agent for De Novo or Transformed Diffuse Large B Cell Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4505-4505 ◽  
Author(s):  
Syed S. Ali ◽  
Gorusu Madhavi ◽  
Kaplan Bruce ◽  
Edwards L. Richard ◽  
Joel Silver ◽  
...  
Keyword(s):  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Duration Of Response ◽  
Transformed Lymphoma ◽  
Large B Cell

Abstract BACKGROUND: 90Y-Ibritumomab is approved for use in relapsed/refractory follicular non-Hodgkin’s lymphoma (NHL), and for transformed lymphoma. It is also being studied in the setting of relapsed diffuse large B cell lymphoma. AIM: To determine response rate and duration, and toxicity of 90Y-ibritumomab in relapsed/refractory diffuse large B-cell (de novo or transformed) lymphoma (DLBCL). METHODS: Permission for the study was obtained from the Institutional Review Boards of St. Francis Hospital and Harford Hospital, Hartford, CT, respectively. Patients who had received 90Y-ibritumomab for DLBCL were identified. A retrospective chart review was conducted to determine patient and disease characteristics, safety and efficacy of 90Y-ibritumomab. RESULTS: A total of 9 individuals received 90Y-ibritumomab between May, 2004, and November, 2006. Their median age was 71 years (48–90 years) and male:female ratio 4:5. Pathology at initial diagnosis was de novo DLBCL (n=4), and follicular (n=4) or small B cell NHL (n=1). The interval to transformation to DLBCL in the latter 5 patients was a median of 7 years (0.5–10 years). At original diagnosis, 5 patients had B symptoms, 3 had bone marrow involvement, 5 had CD10-positivity, 6 had intermediate high or high risk features, and only one had a cytogenetic abnormality (t14;18;22).The median number of prior treatment regimens was 2 (1–3). Seven had received radiation. The last dose of rituximab was administered a median of 9 months (1 week-18 months) previously. Patients were refractory to (n=4) or relapsed after (n=5) the last treatment (chemotherapy and/or rituximab). The median duration of response to last treatment was 2.5 months (1–12 months). The interval from diagnosis of de novo or transformed DLBCL to treatment with 90Y-ibritumomab was a median of 12.5 months (6–35 months). At the time of treatment with 90Y-ibtitumomab, 3 patients had B symptoms, and 4 had <25% bone marrow involvement. The risk status at the time of treatment with ibritumomab was low (n=1), low intermediate (n=2), high intermediate (n=1), and high (n=3) where information was available. There were no non-hematologic or infectious adverse events. The median duration of an absolute neutrophil count <1.5 x 109/L was 4 weeks (0–12 weeks), hemoglobin <10 g/dL 4 weeks (0–12 weeks), and platelet count <100 x 109/L 6 weeks (4–12 weeks). Two patients required platelet and red cell transfusion support. The complete and partial response rates were 11% and 11%, respectively. The duration of response in these 2 patients was 24 months (on-going) and 3 months, respectively. The median progression-free and over-all survival following 90Y-ibritumomab was 3 months and 12 months, respectively. The only patient (de novo DLBCL) who achieved a complete response remains disease-free at this time. She had failed two prior chemotherapy regimens combined with rituximab and was not eligible for stem cell transplantation. CONCLUSIONS: 90Y - ibritumomab is well tolerated in patients with relapsed/refractory DLBCL but response rates are low and response durations short. Outcome was poor whether or not patients had de novo or transformed DLBCL. 90Y-Ibritumomab cannot be recommended as a single agent in relapsed/refractory patients with DLBCL.

Dose-Dense CHOP Plus Rituximab (R-CHOP14) Seems To Overcome, in Large B Cell Lymphoma, the Negative Prognostic Significance of B Cell Origin.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4401-4401 ◽  
Author(s):  
Luigi Rigacci ◽  
Luca Nassi ◽  
Simonetta di Lollo ◽  
Benedetta Puccini ◽  
Morena Doria ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
High Risk ◽  
B Cell ◽  
Clinical Characteristics ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Germinal Centre ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Diffuse large B cell lymphoma (DLBCL) is one of the most common types of lymphoproliferative disorder. Approximately half of all patients will be cured of their disease by primary therapy the remainder die of the disease. Clinical outcome in patients with DLBCL is poorly predictable. Gene-expression profiling in DLCBL has brought an insight into the biological heterogeneity of the disease. Two major subgroups were identified: germinal centre B (GCB) cell, activated B cells (ABC) or non-germinal centre (non-GCB). The GCB group has a significantly better survival than the ABC group. Immunohistochemistry has been evaluated as a surrogate for this molecular classification. The aim of this study was to define retrospectively the B-cell origin of 21 patients treated with R-CHOP14 and to evaluate if the intensified immuno-chemotherapy could improve their clinical outcome. We performed immunohistochemical stains on formalin-fixed paraffin-embedded tissues from diagnostic biopsies with the following antibodies: CD10, bcl-6, bcl-2, MUM1 and Mib1. Based on the algorithm published by Hans et al. we subdivided the patients in GCB origin and ABC origin. We evaluated also the prognostic value of single protein expression. Fourteen patients were male and 9 female, 9 were stage I–II and 12 stage III–IV, 12 presented symptoms at diagnosis and 13 showed bulky disease. Six patients had more than one extranodal sites involved and 13 showed abnormal LDH value, the IPI was intermediate-high risk in 7 and high risk in 3 patients. Half patients presented beta2 microglobulin and ESR elevated. According to immunohistochemistry analysis 9 patients derived from germinal centre and 12 from non-germinal centre, 14 patients presented a positive CD10, 9 a positivity for bcl6, 7 a positive bcl2 and 9 a positive MUM1. Fourteen patients (67%) obtained a complete remission (CR), 4 a partial response (PR) and 3 were non responders (NR). All patients with PR and 2 out 3 NR derived from germinal centre. Four out 14 CR patients experienced relapse, three (75%) derived from non-germinal centre. Six patients died, three derived from GCB and three from non-GCB. After a median period of observation of 500 days (range 98–1870 days) the overall survival (OS) was 71% and the failure free survival (FFS) was 49%. The statistical analysis was performed comparing the B cell origin and clinical characteristics, moreover was also evaluated the expression of bcl2 either in GCB or in non-GCB lymphomas. In univariate and multivariate analysis the overall survival was not affected by clinical characteristics nor B cell origin. In univariate analysis FFS was significantly higher in low and low-intermediate IPI risk patienta (p 0.01) and in multivariate analysis IPI and B cell origin were the only two factors that influenced the FFS. In conclusion even if few patients were evaluated we can point out that the intensification could enhance the efficacy of R-CHOP regimen improving the overall survival also in patients with ABC lymphoma. In contrast it seems that R-CHOP14 does not improve the FFS of patients with ABC origin. Further analysis with larger sample sizes of DLBCL patients are needed to verify this preliminary observations.

scholarly journals BIOMARKER‐DRIVEN TREATMENT STRATEGY IN HIGH RISK DIFFUSE LARGE B‐CELL LYMPHOMA: RESULTS OF A NORDIC PHASE 2 STUDY

2021 ◽  
Vol 39 (S2) ◽  
Author(s):  
S Leppä ◽  
J Jørgensen ◽  
M‐L Karjalainen‐Lindsberg ◽  
K Beiske ◽  
P Nørgaard ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Treatment Strategy ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Phase 2 ◽  
Large B Cell Lymphoma ◽  
Phase 2 Study ◽  
Large B Cell

scholarly journals Survival among patients with relapsed/refractory diffuse large B cell lymphoma treated with single-agent selinexor in the SADAL study

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Marie Maerevoet ◽  
Josee M. Zijlstra ◽  
George Follows ◽  
Rene-Olivier Casasnovas ◽  
J. S. P. Vermaat ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Refractory Status ◽  
Duration Of Response

AbstractPatients with RR DLBCL who have received ≥ 2 lines of therapy have limited treatment options and an expected overall survival (OS) of < 6 months. The SADAL study evaluated single-agent oral selinexor in patients with RR DLBCL and demonstrated an overall response rate (ORR) of 29.1% with median duration of response (DOR) of 9.3 months. The analyses described here evaluated a number of subpopulations in order to understand how response correlates with survival outcomes in order to identify patients who could most optimally benefit from selinexor treatment. Median age was 67 years; 44.8% of patients were ≥ 70 years of age. The median OS was 9.0 months (95% CI 6.2, 13.7) at a median follow-up of 14.8 months. The median OS was not reached in patients with a CR or PR, while patients who did not respond have a median OS of 4.9 months (p < 0.0001). Patients < 70 years had an OS of 11.1 months compared with 7.8 months in patients ≥ 70 years. Among patients with or without prior ASCT, the median OS was 10.9 and 7.8 months, respectively. Among patients with disease refractory to the most recent DLBCL treatment regimen, the median OS was 7.0 months compared with 11.1 months for disease not refractory to the most recent treatment. In a patient population in which survival is expected to be < 6 months, treatment with single-agent oral selinexor was associated with a median survival of 9 months. Increased median OS observed in patients responding to selinexor was consistent across subgroups regardless of age, prior ASCT therapy, or refractory status. Randomized studies of selinexor in combination with a variety of other anti-DLBCL agents are planned. This trial was registered at ClinicalTrials.gov (NCT02227251) on August 28, 2014. https://clinicaltrials.gov/ct2/show/NCT02227251.

A randomized, phase 2 study of R-CHOP plus enzastaurin vs R-CHOP in patients with intermediate- or high-risk diffuse large B-cell lymphoma

2015 ◽  
Vol 57 (1) ◽  
pp. 216-218 ◽  
Author(s):  
John D. Hainsworth ◽  
Edward R. Arrowsmith ◽  
Michael McCleod ◽  
Eric D. Hsi ◽  
Oday Hamid ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Phase 2 ◽  
Large B Cell Lymphoma ◽  
Phase 2 Study ◽  
Randomized Phase 2 ◽  
Large B Cell
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