scholarly journals Efficacy of Tafasitamab (MOR208) Combined with Lenalidomide in Patients with High-Risk Relapsed or Refractory Diffuse Large B-Cell Lymphoma in the L-Mind Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-2
Author(s):  
Eva González-Barca ◽  
Johannes Duell ◽  
Federica Cavallo ◽  
Juan-Manuel Sancho ◽  
Zsolt Nagy ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Refractory Disease ◽  
First Line ◽  
First Line Therapy ◽  
Large B Cell Lymphoma ◽  
Advisory Role

Introduction Patients with diffuse large B-cell lymphoma (DLBCL) that is refractory to primary immunochemotherapy are well recognized as a high-risk population with poor prognosis, and have a typical median overall survival (OS) of 6-13 months [Farooq U, et al. 2017]. Patients with 'double-hit' (MYCand eitherBCL2orBCL6) and 'triple-hit' (MYC, BCL2andBCL6) genetic aberrations are also considered to be a high-risk/poor prognosis group [Davies A. 2019]. Tafasitamab (MOR208) is an Fc-enhanced, humanized, monoclonal anti-CD19 antibody that is under investigation in combination with lenalidomide (LEN) in autologous stem cell transplant (ASCT)-ineligible patients with relapsed/refractory (R/R) DLBCL in the Phase II L-MIND study (NCT02399085) [Salles G, et al. 2020]. We report efficacy data for patients with high-risk DLBCL (primary refractory disease and double/triple-hit lymphoma [DHL/THL]) who received tafasitamab + LEN in L-MIND (data cut-off: Nov 30, 2019; median follow-up for OS, 31.8 months). Methods In the L-MIND study, patients enrolled were aged ≥18 years with R/R DLBCL (1-3 prior systemic therapies, including ≥1 CD20-targeting regimen), with an Eastern Cooperative Oncology Group performance status of 0-2 and ineligible for ASCT. Patients received 28-day cycles of tafasitamab (12 mg/kg intravenously), once weekly during Cycles 1-3 with a loading dose on Cycle 1 Day 4, then every 2 weeks during Cycles 4-12. LEN (25 mg orally) was administered on Days 1-21 of Cycles 1-12. After Cycle 12, progression-free patients received tafasitamab every 2 weeks until disease progression. The primary endpoint was objective response rate (ORR) (partial response [PR] + complete response [CR]), assessed centrally by an independent review committee. Primary refractory disease was defined as no response (CR or PR) to or progression during or within 6 months of frontline DLBCL therapy.MYC,BCL2andBCL6aberrations were determined via fluorescencein situhybridization using tumor biopsy. Results The L-MIND cohort included 15 patients with primary refractory DLBCL and two patients with DHL/THL. Patients with primary refractory DLBCL at baseline had a median age of 73 years (range 48-82; n=9 ≥70 years) and were previously exposed to a median of 2 lines of treatment (range 1-4). Of these patients, ten had stage III/IV disease, ten showed lactate dehydrogenase greater than the upper normal limit, 12 patients had germinal center B-cell DLBCL and eight exhibited intermediate-high or high-risk International Prognostic Index (IPI) status at study baseline. All 15 patients received R-CHOP or equivalent as first-line therapy; two patients previously achieved no response, whereas 13 patients had relapsed within 6 months (ten had achieved a CR and 3 a PR) after frontline therapy. Six patients had received only 1 prior therapy, whereas nine patients had ≥2 lines before L-MIND enrollment. Median time to progression after first-line therapy was 162 days (range 28-182 days); two of 15 patients had progressed within 90 days. Of the 15 patients, 13 were refractory to their last line of therapy before L-MIND. In the 15 patients with primary refractory disease, ORR was 53.3% (95% confidence interval [CI]: 26.6-78.7) and the CR rate was 33.3%, with a 30-month duration of response (DOR) rate of 50% (95% CI: 15.2-77.5) - median DOR not reached (NR). Individual response duration is shown in Figure 1 (swimmer plot): four patients who achieved CR remain in remission after >30 months. Median progression-free survival (PFS) was 5.3 months (95% CI: 0.9-NR) and PFS rate at 30 months was 33.9% (95% CI: 11.0-58.8). Median OS was 13.8 months (95% CI: 1.3-NR) and OS at 36 months was 38.1% (95% CI: 14.6-61.6). Regarding patients with DHL/THL: one with DHL achieved PR only; another patient with THL (also part of the primary refractory subgroup) achieved CR and remains in remission after >30 months. Conclusions The combination of tafasitamab + LEN showed encouraging activity, with a clinically meaningful ORR and CR rate in patients with primary refractory DLBCL, and positive responses in DHL and THL. Patients with primary refractory disease were frequently ≥70 years with stage III/IV disease and poor-risk IPI scores. Although these data should be interpreted with caution due to the small patient subgroup sizes, these clinically relevant results warrant further research with this immunotherapy in patients with difficult-to-treat DLBCL. Disclosures González-Barca: MorphoSys:Other;Janssen:Consultancy, Honoraria;Sandoz:Consultancy;Gilead:Consultancy;Roche:Honoraria;Takeda:Honoraria;Abbvie:Honoraria;Celgene:Consultancy;Kiowa:Consultancy;Celtrion:Consultancy.Duell:Morphosys:Research Funding.Sancho:Bristol-Myers Squibb:Honoraria;Celgene:Consultancy, Honoraria;Gilead:Consultancy, Honoraria;Janssen:Consultancy, Honoraria;Kern-Pharma:Consultancy, Honoraria;Novartis:Consultancy, Honoraria;Roche:Consultancy, Honoraria;Takeda:Honoraria;Celltrion:Consultancy;Sandoz:Consultancy.Nagy:MorphoSys AG:Patents & Royalties.Abrisqueta:Celgene:Consultancy, Honoraria;AbbVie:Consultancy, Honoraria, Speakers Bureau;Roche:Consultancy, Honoraria, Speakers Bureau;Janssen:Consultancy, Honoraria, Speakers Bureau.Panizo:Clínica Universidad de Navarra:Current Employment;Bristol-Myers Squibb, Kyowa Kirin:Speakers Bureau;Janssen, Roche:Membership on an entity's Board of Directors or advisory committees.Augustin:Morphosys:Research Funding;AstraZeneca:Consultancy, Research Funding;Roche:Consultancy;Novartis:Consultancy, Research Funding;Merck:Consultancy;IPSEN:Consultancy, Research Funding;Pfizer:Consultancy, Research Funding;BMS:Consultancy, Research Funding.Weirather:MorphoSys AG:Current Employment.Ambarkhane:MorphoSys AG:Current Employment.Maddocks:Seattle Genetics:Consultancy, Honoraria;Celgene:Consultancy, Honoraria;Pharmacyclics:Consultancy, Honoraria;Morphosys:Consultancy, Honoraria;ADC Therapeutics, AstraZeneca:Consultancy;BMS:Consultancy, Research Funding;Karyopharm:Consultancy.Kalakonda:Celgene:Research Funding.Salles:BMS/Celgene:Honoraria, Other: consultancy or advisory role;Takeda:Honoraria;Karyopharm:Honoraria;Genmab:Honoraria, Other;Debiopharm:Consultancy, Honoraria, Other: consultancy or advisory role;Autolos:Other: consultancy or advisory role;Abbvie:Other: consultancy or advisory role;Roche:Honoraria, Other: consultancy or advisory role;Novartis:Honoraria, Other: consultancy or advisory role;MorphoSys:Honoraria, Other: consultancy or advisory role;Janssen:Honoraria, Other: consultancy or advisory role;Epizyme:Honoraria, Other: consultancy or advisory role;Kite, a Gilead Company:Honoraria, Other: consultancy or advisory role .

scholarly journals Open-Labeled, Multicenter Phase II Study of Bortezomib for Maintenance Therapy in Patients with High Risk Diffuse Large B Cell Lymphoma (DLBCL): Borma Trial from Consortium for Improving Survival of Lymphoma (CISL)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2884-2884
Author(s):  
Jae-Cheol Jo ◽  
Ho Sup Lee ◽  
Cheolwon Suh ◽  
Hye Jin Kang ◽  
Won Seog Kim ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Therapy ◽  
B Cell ◽  
Research Funding ◽  
Maintenance Treatment ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Risk Patients ◽  
Large B Cell Lymphoma ◽  
Risk Patients

Background: High-intermediate or high risk in international prognostic index (IPI) has a long-term chance of cure in the range about 50% in patients with diffuse large B cell lymphoma (DLBCL) treated by R-CHOP. These high risk patients should be considered for additional new treatment to standard R-CHOP or investigational approaches in the context of clinical trials that are designed to ensure that potentially curative therapy. Bortezomib inhibits NF-κB activation through proteasome inhibition, providing rationale for its use in cells that constitutively express NF-κB. Non-germinal center B cell (GCB) DLBCL has a worse survival after upfront chemotherapy and is characterized by constitutive activation of the antiapoptotic NF-κB pathway, which can inhibit chemotherapy. There is no study of bortezomib as maintenance therapy after treated with R-CHOP in high risk patients with DLBCL. So we applied additional bortezomib as maintenance therapy in order to assess improving efficacy and survival rates in high risk patients with non-GCB DLBCL who had been confirmed complete response (CR) after treated with R-CHOP. Methods: Patients with newly diagnosed stage II(bulky)-IV DLBCL with high or high intermediate IPI score of 3 to 5, and patients achieving a CR at the end of 6 or 8 cycles of R-CHOP21 were eligible for enrollment. Non-GCB DLBCL according to Hans criteria confirmed by central review was need before enrollment. Bortezomib maintenance treatment was consisted of bortezomib 1.3mg/m2 subcutaneously administration day 1 and day 15 per 28-day cycle with a total of 12 cycles. The primary endpoint was 3-year progression-free survival (PFS). Secondary endpoints were 3-year overall survival (OS), and toxicites. Toxicity was graded according to the Common Terminology Criteria for Adverse Events v4.0. Results: Fifty-nine patients were enrolled between May 2014 and Oct 2018. The type of Non-GCB DLBCL in all patients was confirmed by the central pathology review. The median age was 65 years (range: 27-86 years), and 60% were > 61 years. The baseline clinical features were as follows: female sex, 45.8%; ECOG >1, 10.2%; stage II bulky (>10cm), 6.8%; stage III/IV, 93.2%. At the time of analysis, 29 patients completed 12-cycles of bortezomib maintenance, and 3 patients is ongoing. Seven patients did not finished maintenance therapy due to toxicities (fatigue, atrial flutter, neuropathy, pleural effusion, thrombocytopenia), and withdrawal of informed consent (n=4). Sixteen patients experienced disease progression during bortezomib maintenance treatment. With a median follow-up of 25.1 months, 3-year PFS rate was 56.9% and 3-year OS rate was 86.4% (Figure 1). Toxicity was assessed in 489 cycles of bortezomib maintenance in all 59 patients. There was no treatment-related death and febrile neutropenia. Conclusion: Bortezomib maintenance showed 3-year PFS rate of 56.9% with acceptable toxicities in patients with high risk DLBCL achieving a CR at the end of 6 or 8 cycles of R-CHOP21. Figure 1 Disclosures Kim: Celltrion: Research Funding; Novartis: Research Funding; J + J: Research Funding; Donga: Research Funding; Kyowa-Kirin: Research Funding; Novartis: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding.

Poor Outcomes Among Patients Failing Dose-Adjusted EPOCH in Aggressive Lymphoma: A Collaborative, Retrospective Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1518-1518 ◽  
Author(s):  
Jackie Vandermeer ◽  
Allison M Winter ◽  
Ajay K. Gopal ◽  
Ryan D. Cassaday ◽  
Brian T. Hill ◽  
...  
Keyword(s):  
B Cell ◽  
Board Of Directors ◽  
Salvage Therapy ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
First Line ◽  
Advisory Committees ◽  
First Line Therapy

Abstract Introduction Among patients with aggressive B-NHL who fail RCHOP, about half respond to standard salvage regimens and may proceed to curative-intent, transplant-based therapy. However, whether pts failing more intensive regimens such as dose-adjusted, infusional EPOCH benefit from standard salvage regimens is unclear. We hypothesized that such patients comprise a higher-risk cohort, facing inferior response rates and outcomes using standard salvage regimens. We undertook a collaborative study to assess response rates and survival among pts failing EPOCH for aggressive B-NHL, to inform patient management and design of clinical trials in this setting. Methods Pharmacy records and institutional databases were queried, identifying pts receiving EPOCH over the last 10 years at the University of Washington/SCCA and the Cleveland Clinic Foundation, for combined analysis. Under IRB approval, patient characteristics, histology, outcome with EPOCH, time to EPOCH failure, response to salvage, and overall survival were analyzed. Diffuse large B cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma, B-cell-lymphoma unclassifiable, HIV-associated B cell lymphoma, and transformed B cell non-Hodgkin lymphoma were included. Pts receiving <2 cycles EPOCH, or who had inadequate follow-up (<3 months), were excluded. Failure of EPOCH was defined as failure to respond or progression during therapy, need for initiation of salvage therapy, or death during therapy of any cause. Adverse events or treatment change due to toxicity were not included in the definition of failure. JMP 11 was used to generate kaplan-meier survival estimates. Results 124 pts with aggressive B-NHL receiving EPOCH were identified. 54 had not relapsed, and among 70 remaining da-EPOCH failures, 37 met the above inclusion criteria. Median age was 55. 27% were female, and 23 received EPOCH as first-line therapy. All but 3 received rituximab with EPOCH. Histologies were primarily DLBCL in 22/37 (60%) and BCL-U in 12/37 (32%) carrying a MYC translocation; most of these harbored additional translocations in BCL2 and/or BCL6 (10/12). However, data regarding MYC rearrangement was not available for all pts. 2 had HIV-associated B-NHL and 3 had PMBCL. With 18 months follow up, the median time to EPOCH failure was 5 months. Only 3 EPOCH failures occurred late (>12 months). Median OS from the date of EPOCH failure was 10 months (Figure 1). Those receiving EPOCH as first-line therapy (23) had a median OS of 14 months from EPOCH failure, as opposed to 4 months for those receiving EPOCH as salvage therapy (log-rank p=.01). Salvage chemotherapy regimens after EPOCH were diverse, and generally ineffective; 6/28 (21%) regimens produced a response (Table 1). Among patients failing EPOCH within a year, platinum-containing salvage (RICE/RDHAP) was effective in only 2/13 patients (15%). 9 patients did not receive any salvage, most of whom died or proceeded to palliative measures and/or hospice care. Conclusions A relatively low overall response rate (21%) was observed in this retrospective analysis of patients failing EPOCH. Analogous to early RCHOP failure in the CORAL study, those failing EPOCH within a year may face inferior outcomes with platinum-based salvage therapy. While combined from two institutions, our data represent a modest sample size and require confirmation. If verified, examination of mechanisms of resistance to EPOCH, and selecting EPOCH failures for clinical trials of novel targeted therapies and transplant-based approaches, may prove critical. Table 1. Salvage Therapy for REPOCH failures Regimen: response/total number treated Notes Response to any salvage: 6/28 (21%) Some patients received more than 1 chemo salvage; responses were tabulated per regimen. RICE: 4/12 2/3 alive post transplant(1 auto 1 allo; 1 declined transplant and survived; 1 died) RDHAP: 1/6 Gemcitabine-based: 0/5 HyperCVAD (Part A and/or B): 1/5 Survivor had CNS only relapse, received regimen B and transplant 9- received no systemic treatmen; most died or proceeded to palliative measures and/or hospice Figure 1. Figure 1. Disclosures Gopal: Gilead: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Spectrum: Consultancy, Research Funding; Emergent/Abbott: Research Funding; Sanofi-Aventis: Honoraria; Seattle Genetics: Consultancy, Honoraria; BioMarin: Research Funding; Piramal: Research Funding; Janssen: Consultancy; Millenium: Honoraria, Research Funding; BMS: Research Funding; Merck: Research Funding. Hill:Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Till:Roche/Genentech: Research Funding; Pfizer: Research Funding.

scholarly journals Young High Risk Patients with MYC/BCL2 Double Hit Lymphoma, BCL2+ and/or Germinal Centre B-Cell like Diffuse Large B-Cell Lymphoma Benefit from Dose-Dense Chemoimmunotherapy Including Early CNS Prophylaxis: Analysis of Data from the Nordic Lymphoma Group CRY-04 and Chic Trials

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2955-2955 ◽  
Author(s):  
Sirpa Leppa ◽  
Judit Jørgensen ◽  
Leo Meriranta ◽  
Klaus Beiske ◽  
Jan M.A. Delabie ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma ◽  
Dose Dense ◽  
In The Beginning ◽  
Large B Cell

Abstract Background. Survival of patients with high-risk diffuse large B-cell lymphoma (DLBCL) is suboptimal, and the risk of central nervous system (CNS) progression is relatively high. We investigated the efficacy of dose-dense chemoimmunotherapy and systemic CNS prophylaxis in two Nordic trials including patients less than 65 years with high-risk DLBCL. We combined individual patient data from these trials to compare clinical outcome and biological prognostic factors in patients treated with CNS prophylaxis given in the beginning (CHIC) versus at the end (CRY-04) of therapy. Patients and methods. In CRY-04 study, patients were treated with six courses of R-CHOEP14 followed by HD-Mtx and HD-Ara-C. In CHIC trial, treatment started with two courses of HD-Mtx in combination with R-CHOP14, followed by four courses of R-CHOEP-14 and one course of R-HD-AraC. In addition, liposomal AraC was administered intrathecally at courses 1, 3 and 5. For the correlative studies, formalin fixed paraffin embedded pretreatment tumor samples were analyzed by fluorescent in situ hybridization for BCL2 and c-MYC breakpoints and by immunochemistry for CD10, BCL6, MUM1, MYC and BCL2 expression. Germinal center B-cell-like (GCB)/non-GCB) subclassification was performed according to Hans algorithm. Results. Among 303 patients enrolled in the trials (CRY-04, n=160 and CHIC, n=143), 295 (CRY-04, n=154 and CHIC, n=139) were evaluable for baseline characteristics and outcome. Median age (54 and 56 years, p=0.222), male/female ratio, stage, and aaIPI scores were comparable in the two cohorts. CHIC regimen improved outcome over CRY-04; the findings included 4-year estimates of PFS (81% vs 66%, p=0.003), OS (83% and 79%, p=ns) and cumulative incidence rates of CNS progression (2.4% and 5.0%, p=ns). Treatment with the CHIC regimen reduced the risk of systemic progression (aaIPI adjusted RR=0.489, 95%CI 0.308-0.777, p=0.002). PFS benefit with CHIC over CRY-04 was observed across pre-specified subgroups, and particularly in patients less than 60 years old (p=0.008). In the entire study population, dual protein expression (DPE) of BCL2 and MYC was the only parameter to be significantly correlated with a worse PFS (4-y PFS 77% vs 50%, p=0.024; RR=2.300, 95% CI 1.088-4.860, p=0.029). Neither any single immunohistochemical marker nor the GCB/non-GCB subtype or MYC/BCL2-translocations significantly affected outcome. However, when treatment interaction was tested, MYC/BCL2 double hit status (DHL; 13%) predicted poor outcome among patients treated with CRY-04 regimen compared with patients who received CHIC regimen (4-y PFS; 38% vs 78%, p=0.086). GCB subtype and BCL2 positivity were also associated with better outcome in the CHIC cohort (4 y PFS; 63% vs 84%, p=0.011 and 61% vs 80%, p=0.007, respectively), whereas there were no significant survival differences between these regimens among the patients with non-GCB subtype, BCL2 negative DLBCL or DPE lymphomas. Conclusions. Our results derived from trial data with homogenous treatment support the use of HD-Mtx in the beginning rather than at the end of therapy. The survival benefit related to CHIC regimen over CRY-04 is due to better systemic control of the disease, and at least partly linked to improved survival among patients with GCB subtype, BCL2 positivity and DHL. Disclosures Leppa: Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Bayer: Research Funding; Roche: Consultancy, Honoraria, Research Funding; Celgene: Consultancy. Holte:Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees; Roche, Norway: Research Funding.

scholarly journals Prognostic significance of infectious episodes occurring during first‐line therapy for diffuse large B‐cell lymphoma ‐ A nationwide cohort study

2020 ◽  
Vol 38 (3) ◽  
pp. 318-325
Author(s):  
Michael R. Clausen ◽  
Sinna P. Ulrichsen ◽  
Maja B. Juul ◽  
Christian B. Poulsen ◽  
Brian Iversen ◽  
...  
Keyword(s):  
Cohort Study ◽  
B Cell ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
First Line ◽  
First Line Therapy ◽  
Large B Cell Lymphoma ◽  
Line Therapy ◽  
Large B Cell
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