Pilot Study of Lenalidomide-Rituximab Combination in Relapsed/Refractory Diffuse Large B Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3695-3695
Author(s):  
Vadim Ivanov ◽  
Diane Coso ◽  
Thérèse Aurran ◽  
Jean Marc Schiano ◽  
Anne-Marie Stoppa ◽  
...  
Keyword(s):  
Clinical Trials ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Induction Phase ◽  
Significant Activity ◽  
Intention To Treat ◽  
Grade 3 ◽  
Initial Results

Abstract Abstract 3695 Despite recent immunochemotherapy advances approximately 50% of DLBCL patients relapse. Data emerging from initial clinical trials demonstrated that Lenalidomide has a significant activity against different subtypes of relapsed/refractory aggressive B-cell lymphoma. Clinical responses are histology subtype-dependent and most prominent in mantle cell lymphoma. The results in DLBCL were less encouraging with ORR of 26%, CR of 9%, PFS of 2.7 mo. Concurrently targeting the tumor cell itself with monoclonal antibody and targeting the immune response and microenvironment with Lenalidomide may be a promising therapeutic strategy. Encouraging by our initial results of Lenalidomide-Rituximab (LR) combination in patient with refractory (R/R) DLBCL (Ivanov V. et al., 2010), Institutional Multidisciplinary Meeting proposed this combination for 17 patients with R/R DLBCL. All pts were refractory to three or more (range: 2–5) previous lines of conventional immuno-chemotherapy. All eligible pts, except 4 primary-refractory, were previously autografted. Median age for the whole group was 62,5 years, (range: 43–79), 5 pts are female. 65% of patients were younger than 65 y. Patients received combination of Rituximab 375 mg/m2 on day 1 or day 7; Lenalidomide (Revlimid), 15 mg/d for the first pt and 25 mg/d for other 16 pts, for 21/28 days. Dexamethasone 40mg, day 1–4 was given for first 7 pts. Initial decision on adding Dexamethasone was based on the extrapolation from the recommended regimen used in multiple myeloma, but it was abandoned in last 10 pts. Initially the treatment duration was established for 6 months, but it was prolonged to 7–11 months for patients in CR. Of 17 pts enrolled on study, 3 patients stopped the treatment during the first course: 1 pt because of grade 3 toxicity and 2 pts because of explosive disease progression. Both patients were switched to palliative care. In 14 pts, received more than 1 course of treatment, 7 (50 %) responded to LR combination, including 6 pts (43%) with CR and 1 (7%) patient with PR. One pt with clinical and PET-FDG scan improvement after 3 courses of LR was included into “auto-allo” tandem program and actually in CR at +12 months after PBSCT. Six pts progressed on LR treatment and were switched to palliative regimens. In intention to treat analysis the CR rate for the whole group was 35%. As regards the follow-up, all 7 pts in PR and CR are evaluable for evaluation. The patient in PR progressed after 5 courses of LR. Six patients in CR group received an average of 8 (range: 7–11) courses of LR treatment. Two patients relapsed after 5 and 26 months of CR and other 4 patients are actually in CR at +7, +17, +18 and +24 months. Adverse events were manageable and the most common toxicity included thrombocytopenia and neutropenia. In relapsed/refractory DLBCL modest initial results of Lenalidomide monotherapy emerge the use of new effective combinations. Recently the combination Lenalidomide-Rituximab (LR) was shown to be highly efficacious in phase 2 study in elderly (>65 y.o.) patients with DLBCL (Zinzani et al., 2011). Into the group of 23 pts the ORR rate at the end of 6-months induction phase was 35%. Our data confirm results of Bologna group in the younger group of patients. Given the poor prognosis of refractory DLBCL, enrolment in already running prospective clinical trials with Lenalidomide are underway and the investigation of the combination of Lenalidomide and Rituximab is further warranted. Disclosures: No relevant conflicts of interest to declare.

Potential Synergic Effect of Lenalidomide-Rituximab Combination: Durable Complete Remissions in Refractory Diffuse Large B Cell Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4989-4989
Author(s):  
Vadim Ivanov ◽  
Diane Coso ◽  
Therese Aurran-Schleinitz ◽  
Jean-Marc Schiano de Colella ◽  
Anne-Marie Stoppa ◽  
...  
Keyword(s):  
Clinical Trials ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Published Data ◽  
Significant Activity ◽  
Antitumor Effects ◽  
Histologic Subtype ◽  
Initial Results

Abstract Abstract 4989 Data emerging from initial clinical trials demonstrated that Lenalidomide has a significant activity against different subtypes of aggressive B-cell lymphoma. Clinical responses are histologic subtype-dependent and most prominent in mantle cell lymphoma. The results in DLBCL were less encouraging with ORR of 26%, CR of 9%, PFS of 2.7 mo. Concurrently targeting the tumor cell itself with monoclonal antibody and targeting the immune response and microenvironment with Lenalidomide may be a promising therapeutic strategy. By modulating the immune system through dendritic cells and NK cells, by changing the cytokine milieu, and by their anti-angiogenic effects, IMiDs in combination with rituximab resulted in augmented in vitro and vivo antitumor effects against B-cell lymphoma. Recently the combination Lenalidomide-Rituximab (LR) was shown to be highly efficacious in follicular NHL. Encouraging by our initial results of LR combination in patient with refractory (R/R) DLBCL (Leuk Lymphoma 2010), Institutional Multidisciplinary Meeting proposed this combination for other 8 patients with R/R DLBCL. All patients were refractory to three or more previous lines of conventional immuno-chemotherapy. All except 3 primary-refractory pts were previously autografted. Patients received combination of Rituximab 375 mg/m2, day 1 or day 7; Lenalidomide (Revlimid), 15 mg/d for the first pt and 25 mg/d for other 8 pts, for 21 days. Dexamethasone 40mg, day 1–4 was given for first 6 pts. Initial decision on adding Dexamethasone was based on the extrapolation from the recommended regimen used in multiple myeloma, but it was abandoned in last 3 pts. Of 9 pts enrolled on study, 8 received > 2 cycles of LR and all of them were evaluable for response. Median age for evaluable pts was 52 (range: 19–73), 3 pts are female. Of 8 evaluable pts, 5 (63%) responded to LR, including 3 pts (38%) with CR and 2 (25%) patients with PR. These two PR pts were primary refractory to chemotherapy before LR and both were grafted (1 auto and 1 allo) after three courses of LR. One pt with clinical and PET-FDG scan improvement after 3 courses of LR was included into “auto-allo” tandem program and actually in CR after PBSCT. Two pts progressed on LR treatment and were switched to palliative regimens. As regards the follow-up, 3 pts in CR are evaluable for evaluation. Two pts received 6 and one pt 8 courses of RL treatment. One patient relapsed after 24 mo of CR and other 2 patients are in CR at +11 and +6 months. In relapsed/refractory DLBCL modest initial results of lenalidomide monotherapy emerge the use of new effective combinations. Recently several phase II studies of LR efficacy in indolent NHL were proposed. For instance, there is no published data of long-term safety and efficacy of this combination in DLBCL. Given the poor prognosis of refractory DLBCL, enrolment in already running prospective clinical trials with lenalidomide are underway and the investigation of the combination of Lenalidomide and Rituximab is further warranted. Disclosures: No relevant conflicts of interest to declare.

Rituximab, gemcitabine and oxaliplatin (R-GEMOX): An effective regimen for relapsed and refractory B-cell lymphoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7562-7562 ◽  
Author(s):  
T. El Gnaoui ◽  
J. Dupuis ◽  
K. Belhadj ◽  
A. Rahmouni ◽  
C. Copie-Bergman ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Median Number ◽  
Primary Objective ◽  
Clinical Activity ◽  
High Dose ◽  
Induction Phase ◽  
Mantle Cell ◽  
Grade 3

7562 Background: High-dose therapy with autologous stem cell support (HDT) is an established treatment for chemosensitive relapse in lymphoma. However, not all patients are candidates for HDT because of age, comorbidities or previous HDT. In addition,effective and less toxic alternatives to classical Cisplatin/ARA-C-based salvage regimens are needed. Methods: Based on the clinical activity, tolerability of rituximab (R), gemcitabine (G) and oxaliplatin (Ox) and synergy between these drugs, the R-GEMOX regimen was designed with R (375mg/m2 d 1), G (1,000 mg/m2 d 2) and Ox (100 mg/m2 d 2). Treatment was given every two weeks. Between January 2002 and June 2005, 46 patients with refractory/relapsing B-cell CD20+ lymphoma not eligible for HDT were enrolled in an unicenter pilot study whose primary objective was overall response rate (ORR) after 4 cycles (induction phase). Patients were planned to receive 8 cycles if at least PR was observed after 4 cycles. Median age was 64 years (range: 43–78) and histological subtypes were: diffuse large B-cell lymphoma (n = 33), follicular (n = 8) and mantle cell (n = 5). Prior treatments included anthracyclin in 45 patients, rituximab in 26 (56%) and HDT in 14 (30%). The median number of prior treatments was 2 (range: 1 to 5) and 13 patients (28%) had received at least 3 prior regimens. Results: 315 cycles were given. The dose administered was 100% of the intended dose for the three drugs in all patients but 8, for whom the dose of oxaliplatin was reduced due to neurotoxicity (n = 7) or preexisting renal insufficiency (n = 1). Eight patients progressed during the induction phase. After 4 cycles, responses were: 10 CR, 13 CRu and 15 PR resulting in an ORR of 83%. At the end of treatment, among the 38 responder-patients, 36 patients achieved CR (78% of the entire population), one patient remained in PR and one progressed. With a median follow-up of 27 months, the 2-year progression-free and overall survivals were 53% and 66%, respectively. NCIC grade 3–4 neutropenia and thrombocytopenia were reported in 48% and 22% of the cycles. A grade 4 infection was observed in only 3% of the cycles. There was no renal toxicity. Conclusions: The R-GEMOX regimen shows promising activity with an acceptable toxicity. It is currently evaluated in a multicentric phase II study. [Table: see text]

scholarly journals The biology behind B-cell lymphoma 2 as a target in chronic lymphocytic leukemia

2016 ◽  
Vol 7 (6) ◽  
pp. 321-329 ◽  
Author(s):  
Valentín Ortíz-Maldonado ◽  
Pablo Mozas ◽  
Julio Delgado
Keyword(s):  
Clinical Trials ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Mitochondrial Pathway ◽  
Therapeutic Agents ◽  
Lymphocytic Leukemia ◽  
Hallmarks Of Cancer ◽  
Lymphoid Malignancies

B-cell lymphoma 2 (BCL2)-type proteins are key regulators of the intrinsic or mitochondrial pathway for apoptosis. Since escape from apoptosis is one the main ‘hallmarks of cancer’, BCL2 inhibitors have emerged as promising therapeutic agents for diverse lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL). Multiple clinical trials have shown efficacy of these agents in patients with relapsed/refractory disease with a favorable toxicity profile. Moreover, some clinical trials indicate that combination with monoclonal antibodies and other novel agents may enhance their effect.

scholarly journals MicroRNA Signatures In B-Cell Lymphomas

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4155-4155
Author(s):  
Lorena Di Lisio ◽  
Margarita Sanchez-Beato ◽  
Gonzalo Gomez-Lopez ◽  
Maria E. E. Rodriguez ◽  
Santiago Montes-Moreno ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cell ◽  
Burkitt Lymphoma ◽  
Gene Expression Regulation ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoid Tissues ◽  
Molecular Features ◽  
Lymphoma Type

Abstract Abstract 4155 Beyond the conventional criteria of lymphoma classification (integrated clinical, morphological, immunophenotypic, and molecular features) additional markers are still required for a more precise differential diagnosis and a better understanding of lymphoma pathogenesis. MicroRNAs (miRNA) are non-coding small RNAs that play an important role in gene expression regulation, contributing to cell differentiation and tumorigenesis. Specifically, miRNAs have been already described to play a relevant role in B cell differentiation, and in some cases proposed to constitute lymphoma-type specific markers and possible therapeutic targets. We explore the potential diagnostic application of miRNA expression in a large series of 147 cases including all B-cell non-Hodgkin lymphomas (NHL) major types and appropriate controls. As an example of a practical application, data were also used to identify miRNAs differentially expressed when comparing Burkitt Lymphoma (BL) and Diffuse Large B-Cell Lymphoma (DLBCL) in paraffin-embedded samples. Each lymphoma type (BL, CLL, DLBCL, FL, MCL, MZL/MALT, NMZL and SMZL) was compared to the whole series of NHL by Significant Analysis of Microarray (SAM) method. The analysis identified a set of 128 characteristic miRNAs (FDR<0.01 and Fold change >1.5 log2). All lymphoma types were characterized by specific miRNA signatures, reflecting cell of origin and/or discrete oncogene alterations. Of interest is also the comparison with reactive lymphoid tissues, since it revealed a specific B-cell lymphoma miRNA profile, which includes a cluster of downregulated miRNAs, such as let7 family, miR-1 and miR-200 family. Burkitt Lymphoma was also directly compared to DLBCL, and 43 miRNA selected by SAM analysis were studied in a new series of 28 BL and 43 DLBCL samples using quantitative RT-PCRIn this second step, the differential expression of a set of 19 miRNAs was confirmed between BL and DLBCL. (FDR < 0.05 after t-test (limma)). These findings expand the potential diagnostic markers in lymphoma diagnosis and provide useful information on lymphoma pathogenesis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Perceptions of Community Hematologists/Oncologists on Barriers to Chimeric Antigen Receptor T-Cell Therapy for the Treatment of Diffuse Large B-Cell Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2198-2198
Author(s):  
Ajeet Gajra ◽  
Richard Sweat ◽  
Yolaine Jeune-Smith ◽  
Jonathan K. Kish ◽  
Bruce A Feinberg
Keyword(s):  
Clinical Trials ◽  
B Cell ◽  
Annual Meeting ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
The United States ◽  
Large B Cell Lymphoma ◽  
Car T

Introduction The ASH Annual Meeting is a venue for presentation of outcomes data from key clinical trials in hematologic malignancies and novel drug classes used to treat them. The approval of two CAR-T therapies, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel), in the treatment of large B-cell lymphoma (LBCL), including diffuse LBCL (DLBCL), has ushered in a new class of drugs, i.e. cellular therapy. At ASH 2018, Nastoupil et al. presented data from a retrospective analysis of the characteristics and outcomes of patients with relapsed/refractory LBCL, including DLBCL, treated with commercially available axi-cel CAR-T therapy at academic centers in the United States (Nastoupil LJ, et al. Blood. 2018;132[Suppl 1]:91). The authors found that early outcomes of real-world patients receiving axi-cel therapy were comparable to those observed in the clinical trial population, despite >40% of these patients failing to meet the clinical trial eligibility criteria. At a live meeting in February 2019, we sought the perceptions of community hematologists and oncologists (H/O) regarding their use of, referrals for and barriers to CAR-T therapy as well their perception of the value of the real-world evidence (RWE) presented. Methods A live meeting in February 2019 convened H/O with geographic representation from across the United States. The participants were shown data from selected oral and/or poster presentations from the 2018 ASH Annual Meeting and responded to questions regarding their perceptions of the data and its potential impact on current practice. Participants submitted their demographic responses via a web-based survey prior to the meeting and data impression responses via an audience response system at the live meeting. Results Among the 59 H/O who participated in this live market research program on February 22-23, 2019, 61% identified their primary specialty as hematology/oncology and 34% medical oncology. Only 27% of H/O had attended the 60th ASH Annual Meeting in December 2018. The participants were mostly community-based physicians, 50% in private community and 45% in community practices owned by a hospital or academic center. One-third have been in practice for over 20 years, one-third for 11-20 years and one-third for 10 or fewer years. This group sees an average of 20+ patients per day and reported B-cell non-Hodgkin lymphoma as one of the three most common hematologic malignancy they managed. 28% of H/O indicated that they have referred one patient and 24% have referred 2-5 patients for CAR-T therapy since the first approval on August 30, 2017. Of those H/O who had referred patients for CAR-T therapy, 45% indicated that none of their patients had yet received the infusion. The top two barriers to prescribing/recommending CAR-T therapy, as reported by the H/O, were the cumbersome logistics of administering therapy and following patients (52%), and the cost of the therapy (46%). Other concerns included high toxicity (24%) and lack of long-term survival data (19%), but not lack of knowledge of CAR-T therapy (2%). Furthermore, 87% of H/O agreed with the assertion that due to the limitations of randomized clinical trials, RWE is necessary to inform clinical practice. After review of the information presented on the real-world use of axi-cel, 73% of H/O indicated that this information is likely to cause them to recommend CAR-T therapy for more of their patients with DLBCL. Conclusions There is significant interest in adopting and using CAR-T therapies in LBCL amongst community H/O. This group does not perceive itself as lacking in knowledge regarding CAR-T therapy. The significant barriers of logistics and cost are potential deterrents to appropriate use. These results can inform stakeholders (manufacturers, payers, hospitals and practices) regarding the need to improve processes and develop payment models to address cost in order to facilitate access of these agents to the appropriate patients. RWE is viewed favorably by the vast majority of community H/O to inform clinical practice, due to the limitations of randomized clinical trials. Disclosures Gajra: Cardinal Health: Employment. Sweat:Cardinal Health: Employment. Jeune-Smith:Cardinal Health: Employment. Kish:Cardinal Health: Employment. Feinberg:Cardinal Health: Employment.

IVAC +/- R for Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas: Real-World Experience in the Modern Era

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-10
Author(s):  
Michael J Buege ◽  
Phuong H Dao ◽  
Esther Drill ◽  
Andréa C LeVoir ◽  
Terry Pak ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Board Of Directors ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hematologic Toxicity ◽  
Low Grade ◽  
Advisory Committees ◽  
Prophylactic Measures ◽  
Grade 3

Introduction Part B of the modified Magrath regimen (ifosfamide, etoposide, and cytarabine; IVAC) with or without rituximab (R) is utilized as a standalone regimen in the management of relapsed/refractory Burkitt lymphoma and other non-Hodgkin lymphomas (NHL). There are no comparative or prospective data and a paucity of retrospective, non-comparative data to support use of this regimen. A small retrospective study described second-line IVAC use without R in a mixed cohort of patients with diffuse large B-cell lymphoma (DLBCL) or peripheral T-cell lymphoma, suggesting utility as a bridge to hematopoietic cell transplantation (HCT) (Pereira J, et al. Leuk Res. 2006 Jun;30(6):681-5). The activity of this regimen in B-cell NHL, particularly in conjunction with R, and its toxicity remain incompletely described. In this study, we describe our institutional experience with IVAC +/- R in relapsed/refractory B-cell NHL. Methods We reviewed all patients with relapsed/refractory B-cell NHL treated with IVAC +/- R between 1 January 2004 and 30 September 2019 at Memorial Sloan Kettering Cancer Center to assess efficacy and toxicity. Patients who received IVAC as part of sequential or alternating chemotherapy were excluded. Standard dosing consisted of ifosfamide 1500mg/m2 IV over 60min days 1-5, etoposide 60mg/m2 IV over 60min days 1-5, cytarabine 2000mg/m2 IV over 3 hours every 12 hours days 1-2, with or without rituximab 375mg/m2 IV day 0 or 1 in 21- to 28-day cycles (Lacasce A, et al. Leuk Lymphoma. 2004 Apr;45(4):761-7). Results Cohort and treatment characteristics are described in Table 1. Among 54 eligible patients (median age 51 years), 76% had DLBCL; 30% had lymphomatous central nervous system involvement at the time of initiating IVAC. Patients had received median 2 prior lines of therapy, with the last dose of the most recent line of therapy administered a median of 3 weeks prior to initiating IVAC. Patients received median 2 cycles of IVAC +/- R; 48% received IVAC-R. Prophylactic antimicrobials with cycle 1 were utilized in 94%. Most patients received herpesvirus- (81%) and Pneumocystis- (80%) directed prophylaxis; broad-spectrum prophylaxis with a fluoroquinolone was less common (24%). Primary granulocyte colony stimulating factor (GCSF) was utilized in 93% of patients with cycle 1; primary or secondary GCSF was utilized in 94% of cycles. Efficacy outcomes are described in Table 1. Objective response rate (ORR) among 46 evaluated patients was 48%; 17% achieved CR. ORR did not vary significantly between patients who did or did not receive R (58% vs 42%; p = 0.5) but was associated with number of IVAC cycles administered (among responders, 69% received 3-4 cycles while 31% received 1-2 cycles; p < 0.001). At median follow-up of 22 months, median progression-free survival (PFS) and overall survival (OS) were 3.1 months and 4.9 months, respectively (Figure). In Cox proportional hazard regression analysis of survival, patients who received R with every cycle (p = 0.025) and received 3 or more cycles (p < 0.001) experienced significantly longer PFS. Patients who achieved CR (p < 0.001) or PR (p = 0.003), received R with every cycle (p < 0.001), received 3 or more cycles (p < 0.001), or underwent subsequent HCT or CAR-T cell therapy (p = 0.001) experienced significantly longer OS. Toxicity outcomes are described in Table 2. Grade ≥ 3 anemia (93%), neutropenia (94%), and thrombocytopenia (100%; all grade 4) were common, regardless of number of cycles received. Febrile neutropenia (FN) occurred in 65% of patients and complicated 47% of cycles; documented infection occurred in 44%. Risk of FN and infection did not appear to be influenced by use of antimicrobial or GCSF prophylaxis. Grade ≥ 3 elevations in AST/ALT or total bilirubin were uncommon (5.6% and 9.3%, respectively). Neurotoxicity attributed to cytarabine or ifosfamide occurred in 17% of patients and was usually low-grade; hemorrhagic cystitis occurred in one patient. In patients for whom cause of death was documented (n = 37), mortality was attributed to a treatment-related complication in 19%. Conclusion IVAC-R may be a useful bridging therapy for patients with relapsed/refractory B-cell NHL who are planned for HCT. However, its potential for profound hematologic toxicity and life-threatening complications despite prophylactic measures requires careful consideration of less toxic alternatives. Disclosures Straus: Elsevier: Membership on an entity's Board of Directors or advisory committees, Other: CME writer; Targeted Oncology: Consultancy, Speakers Bureau; Imedex, Inc.: Speakers Bureau; NY Lymphoma Rounds: Consultancy; Takeda Pharmaceuticals: Research Funding, Speakers Bureau; Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees; OncLive: Speakers Bureau; ASH: Other: Conference in December 2019 on HL to other physicians during ASH; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Clinical efficacy and molecular biomarkers in a phase II study of tucidinostat plus R-CHOP in elderly patients with newly diagnosed diffuse large B-cell lymphoma

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Mu-Chen Zhang ◽  
Ying Fang ◽  
Li Wang ◽  
Shu Cheng ◽  
Di Fu ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Molecular Biomarkers ◽  
Newly Diagnosed ◽  
Large B Cell Lymphoma ◽  
Grade 3 ◽  
Large B Cell

Abstract Background Elderly patients with diffuse large B-cell lymphoma (DLBCL) present with poor clinical outcome and intolerance to intensive chemotherapy. Histone deacetylase inhibitors (HDACIs) show anti-lymphoma activities and can be applied to treat DLBCL. This study aimed to evaluate efficacy and safety of oral HDACI tucidinostat (formerly known as chidamide) plus R-CHOP (CR-CHOP) in elderly patients with newly diagnosed DLBCL (International Prognostic Index ≥ 2). Results Among 49 patients, the complete response rate was 86%, with overall response rate achieving 94%. The 2-year progression survival (PFS) and overall survival (OS) rates were 68% (95% CI 52–79) and 83% (95% CI 68–91). Comparing with historical control (NCT01852435), the 2-year PFS and OS rates of double-expressor lymphoma phenotype (DEL) were improved, and negative prognostic effect of histone acetyltransferases CREBBP/EP300 mutations was also mitigated by CR-CHOP. Grade 3–4 neutropenia was reported in 171, grade 3–4 thrombocytopenia in 27, and grade 3 anemia in 11 of 283 cycles. No grade 4 non-hematological adverse event was reported. Conclusion CR-CHOP is effective and safe in elderly patients with newly diagnosed DLBCL. Relevance of DEL phenotype and molecular biomarkers on CR-CHOP response warrants further investigation in DLBCL. Trial registration ClinicalTrial.gov, NCT02753647. Registered on April 28, 2016.

scholarly journals Parsaclisib, a potent and highly selective PI3Kδ inhibitor, in patients with relapsed or refractory B-cell malignancies

Blood ◽  
2019 ◽  
Vol 133 (16) ◽  
pp. 1742-1752 ◽  
Author(s):  
Andres Forero-Torres ◽  
Radhakrishnan Ramchandren ◽  
Abdulraheem Yacoub ◽  
Michael S. Wertheim ◽  
William J. Edenfield ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
B Cell ◽  
Cell Lymphoma ◽  
Phase 1 ◽  
Objective Response ◽  
B Cell Lymphoma ◽  
Janus Kinase ◽  
B Cell Malignancies ◽  
Once Daily ◽  
Grade 3

Abstract This phase 1/2 study assessed parsaclisib (INCB050465), a next-generation, potent, and highly selective phosphatidylinositol 3-kinase δ (PI3Kδ) inhibitor, in patients with relapsed or refractory B-cell malignancies, alone or in combination with a Janus kinase 1 inhibitor (itacitinib) or chemotherapy (rituximab, ifosfamide, carboplatin, and etoposide). Seventy-two patients received parsaclisib monotherapy (5-45 mg once daily). Expansion doses were 20 and 30 mg once daily; intermittent dosing at 20 mg (once daily for 9 weeks, then once weekly) was explored. No dose-limiting toxicities were identified, and maximum tolerated dose was not reached. Most common nonhematologic treatment-emergent adverse events (TEAEs) were diarrhea/colitis (36%), nausea (36%), fatigue (31%), and rash (31%). Grade 3/4 neutropenia occurred in 19% of patients. Serious TEAEs (>2 patients) were diarrhea/colitis (n = 9), pyrexia (n = 4), hypotension (n = 3), and sepsis (n = 3). Aspartate and alanine transaminase elevations occurring before treatment discontinuation were grade 1, except 1 grade 3 event each, secondary to sepsis. Two patients experienced 3 fatal parsaclisib-unrelated TEAEs (respiratory failure; respiratory failure and sepsis). In non-Hodgkin lymphoma (NHL), objective response rates to monotherapy were 71% in follicular lymphoma, 78% in marginal zone lymphoma, 67% in mantle cell lymphoma, and 30% in diffuse large B-cell lymphoma; 93% of responses occurred at first assessment (∼9 weeks). Parsaclisib has demonstrated antitumor activity in relapsed or refractory B-cell NHL with the potential for improved long-term patient outcomes. Phase 2 studies in relapsed or refractory B-cell NHL subtypes are ongoing. This trial was registered at www.clinicaltrials.gov as #NCT02018861.

scholarly journals Rituximab-CHOP With Early Rituximab Intensification for Diffuse Large B-Cell Lymphoma: A Randomized Phase III Trial of the HOVON and the Nordic Lymphoma Group (HOVON-84)

2020 ◽  
Vol 38 (29) ◽  
pp. 3377-3387
Author(s):  
Pieternella Johanna Lugtenburg ◽  
Peter de Nully Brown ◽  
Bronno van der Holt ◽  
Francesco A. D’Amore ◽  
Harry R. Koene ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
Phase Iii ◽  
Free Survival ◽  
Intention To Treat ◽  
Large B Cell Lymphoma ◽  
Large B Cell

PURPOSE Immunochemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has become standard of care for patients with diffuse large B-cell lymphoma (DLBCL). This randomized trial assessed whether rituximab intensification during the first 4 cycles of R-CHOP could improve the outcome of these patients compared with standard R-CHOP. PATIENTS AND METHODS A total of 574 patients with DLBCL age 18 to 80 years were randomly assigned to induction therapy with 6 or 8 cycles of R-CHOP-14 with (RR-CHOP-14) or without (R-CHOP-14) intensification of rituximab in the first 4 cycles. The primary end point was complete remission (CR) on induction. Analyses were performed by intention to treat. RESULTS CR was achieved in 254 (89%) of 286 patients in the R-CHOP-14 arm and 249 (86%) of 288 patients in the RR-CHOP-14 arm (hazard ratio [HR], 0.82; 95% CI, 0.50 to 1.36; P = .44). After a median follow-up of 92 months (range, 1-131 months), 3-year failure-free survival was 74% (95% CI, 68% to 78%) in the R-CHOP-14 arm versus 69% (95% CI, 63% to 74%) in the RR-CHOP-14 arm (HR, 1.26; 95% CI, 0.98 to 1.61; P = .07). Progression-free survival at 3 years was 74% (95% CI, 69% to 79%) in the R-CHOP-14 arm versus 71% (95% CI, 66% to 76%) in the RR-CHOP-14 arm (HR, 1.20; 95% CI, 0.94 to 1.55; P = .15). Overall survival at 3 years was 81% (95% CI, 76% to 85%) in the R-CHOP-14 arm versus 76% (95% CI, 70% to 80%) in the RR-CHOP-14 arm (HR, 1.27; 95% CI, 0.97 to 1.67; P = .09). Patients between ages 66 and 80 years experienced significantly more toxicity during the first 4 cycles in the RR-CHOP-14 arm, especially neutropenia and infections. CONCLUSION Early rituximab intensification during R-CHOP-14 does not improve outcome in patients with untreated DLBCL.

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