Cyclophosphamide , Vincristine And Prednisone Research Articles

Case report: Sustained complete remission with ivosidenib in a patient with relapsed, IDH1-mutated acute leukemia

Older patients with acute lymphoblastic leukemia (ALL) have a poor prognosis, with a 5-year overall survival rate of only 10%–20%. This is attributable to patient comorbidities, poor performance status, and high-risk disease biology. The prognosis for patients with relapsed/refractory (R/R) disease remains poor, particularly for patients who are not candidates for therapies targeting CD19 or CD22. Additional treatment options are needed for these patient populations. The patient presented here is a 76-year-old man diagnosed with precursor B-cell ALL with aberrant expression of myeloid markers and lacking significant CD19 or CD22 expression. A 3-year remission was achieved with one cycle of CVP (cyclophosphamide, vincristine, and prednisone) followed by 22 months of maintenance DOMP (dexamethasone, vincristine, methotrexate, and 6-mercaptopurine) prior to relapse. He was then treated with one cycle of salvage CVP, which was complicated by a stroke resulting in hemiparesis. Next-generation sequencing (NGS) was performed on the relapsed bone marrow, which revealed the presence of an R132H mutation in the isocitrate dehydrogenase 1 (IDH1) gene. He was subsequently treated with the IDH1 inhibitor ivosidenib and remained in a second remission for nearly 1 year. IDH1 mutations are present in up to 14% of acute myeloid leukemia (AML) cases but are also seen more rarely in ALL, particularly in cases involving aberrant expression of myeloid markers. Ivosidenib has demonstrated efficacy in patients with IDH1-mutated AML but has not been extensively studied in other hematologic malignancies. This case demonstrates the role of NGS in revealing treatment options in patients with otherwise limited available therapies.

The Short-Term Efficacy and Safety of Obinutuzumab Plus Chemotherapy in B-NHL with High Tumor Burden: A Real-World, Retrospective Study

Introduction: The prognosis of patients with B-cell non-Hodgkin's lymphoma (B-NHL) in high tumor burden is significant poor and patients frequently occur tumor lysis syndrome (TLS) during chemotherapy. There are no standard treatment regimens at present, so it is very crucial to explore effective treatment options to improve prognosis. The aim of present study is to analysis the short-term efficacy and safety of obinutuzumab plus chemotherapy in B-NHL with high tumor burden. Methods: We retrospectively investigated the records of 19 patients of B-NHL with high tumor burden and received obinutuzumab treatment at the First Hospital of Jilin University from November 2021 to July 2022, including 9 marginal zone lymphoma (MZL), 7 chronic lymphocytic leukemia /small lymphocytic lymphoma (CLL/SLL), 2 mantle cell lymphoma (MCL), 1 B-prolymphocytic leukemia (B-PLL). All patients received obinutuzumab at a dose of 1000 mg (on days 1, 8, and 15 of cycle 1 and on day 1 of subsequent cycles). The primary endpoint was objective response rates (ORR), and secondary endpoints was incidence of adverse events (AEs). Results: This study enrolled 19 patients completed ≥ 1cycles obinutuzumab plus chemotherapy, including 8 patients with initial treatment and 11 with relapsed and refractory (R/R). Among them, 15 received obinutuzumab with bendamustine (BG), 3 with Bruton tyrosine kinase inhibitors (G-BTKi), 1 with COP (cyclophosphamide, vincristine, and prednisone; G-COP). The median age was 65 years (range, 41-83 years); 12 males and 7 females. In addition, 94.7% patients (18/19) were identified with advanced stage; 73.7% (14/19) with B symptoms; 52.6% (10/19) with ECOG ≥ 2; 57.9% (11/19) with elevated lactate dehydrogenase (LDH) levels; 100% with elevated beta-2 microglobulin (β2MG) levels. 94.7% patients could quickly relieve the high tumor burden status after 1cycle obinutuzumab treatment (Figure 1A). Furthermore, there are 6 patients with hyperleukocytosis (blood cell count greater than 100,000/mL), all reduce to normal level on day 4 of obinutuzumab treatment (Figure 1B); 12 patients with splenomegaly, including 11 massive splenomegaly (long axis >20 cm), all significantly decreased after obinutuzumab treatment, and 7 patients has returned to normal level, and patients with enlarged lymph nodes also significantly reduced after obinutuzumab treatment (Figure 1C). Besides, 8 patients measured minimal residual disease (MRD) in peripheral blood and 6 (75%) achievement of undetectable MRD. Significantly, the ORR was 94.7% (18/19), and 57.9% (11/19) achieved complete remission by evaluation of images. (Figure 1D). The most common AE of any grade were infusion-related reactions 7/19 (36.8%); expiratory dyspnea 2/19 (10.5%); nausea 1/19 (5.3%). In addition, 9/19(47.4%) neutropenia, which may also associate with chemotherapy. There was no incidence of AEs leading to treatment withdrawal or death under obinutuzumab plus chemotherapy treatment. Conclusions: Obinutuzumab could quickly relieve the high tumor burden status and decrease the occurrence of TLS. Thus, obinutuzumab is a promising treatment in patients of B-NHL with high tumor burden. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Long-Term Outcomes of Patients Aged 65 Years or Older with Peripheral T-Cell Lymphoma, Not Otherwise Specified (PTCL-NOS) and T-Follicular Helper T-Cell Lymphoma (TFHTCL) Treated with Curative Intent CHOP(like) Chemotherapy

Introduction CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) remains the standard treatment for older adults with non-anaplastic large cell lymphoma (ALCL), nodal peripheral T-cell lymphomas (PTCLs). However, recent studies suggest that patients (pts) > 75 years (y) have similar outcomes with CHOP compared to those receiving palliative regimens (Ellin et al. Hematological Oncology 2017). In addition, with studies demonstrating sensitivity of PTCLs to epigenetic therapies, especially in the T-follicular helper (TFH) subtypes, there are emerging clinical trials evaluating these agents in newly diagnosed PTCL patients > 60 y (NCT02232516). We evaluated the long-term outcomes of pts aged 65 y or older with PTCLs, a group generally not transplant eligible, treated with systemic therapy with a focus on those treated with curative intent CHOP(like) chemotherapy. Methods The BC Cancer Lymphoid Cancer Database was reviewed and pts > 65 years with PTCL, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL) as well as other T-Follicular Helper PTCL (collectively referred to as TFH T-cell lymphoma [TFHTCL]) diagnosed between 2000-2021 and who received front-line chemotherapy were included. Diagnoses were based on the World Health Organization (WHO) classifications of 2001, 2008, and 2017, depending on the era of diagnosis. Time to progression (TTP) was measured from the date of pathologic diagnosis to the date of relapse/progression, death due to treatment toxicity or lymphoma. Results 152 pts were initially identified, of which 5 were excluded: stage IA/IAE (n=3); CNS involvement only (n=2). Of the remaining 147 pts, 67 (46%) had PTCL-NOS and 80 (54%) had TFHTCL. The median age was 74 y (range 65-90) and the majority of pts had high risk features: International Prognostic Index (IPI) score of > 3 (n=113, 76%), stage III/IV disease (n=136, 93%) and PS of > 2 (n=85, 58%). Most pts (n=127, 86%) received multi-agent chemotherapy with curative intent. All pts received CHOP/CHOP-like chemotherapy (including five pts treated with CHP-brentuximab vedotin)Over half of these patients (n=66, 52%) received attenuated doses of chemotherapy starting from cycle 1, typically 50-75% dose intensity. Only two patients received consolidative autologous stem cell transplant. The remaining 20 patients received chemotherapy with palliative treatment intent, the majority (n=18, 90%) receiving cyclophosphamide alone or with the CVP (cyclophosphamide, vincristine, and prednisone) regimen. The median follow-up of all pts using the reverse Kaplan-Meier method was 9.2 y (range 0.9 to 12.5). The estimated 5-y TTP and overall survival (OS) for all patients were 21%, and 26%, respectively. Outcomes were similar in PTCL-NOS and TFHTCL (5-y TTP 17% vs 25%; p = 0.26). Curative intent chemotherapy was used more frequently in the 65-74 y vs > 75 y age group (70% vs 36%, p = 0.004). As expected, outcomes were superior in those treated with curative intent (Table 1): Median TTP of 11.3 months (m) vs 3.0 m; median OS of 24 m vs 4.5 m. Improvements in TTP and OS extended to those > 75 y (p < 0.001 for both). Considering the curative intent cohort, 91% of the relapse/progression events occurred within the first 3 y, and there was no significant difference in outcomes (5-y TTP/OS) with increasing age: 65-75 (19%/25%), >75 (34%/35%) (p = 0.08/0.6). Further, the outcomes of pts who received attenuated doses of CHOP-like chemotherapy were not inferior compared to full dose chemotherapy (5-y TTP/OS 32%/37% vs. 17%/21% p= 0.2/0.3). 5-y TTP/OS by the IPI ranged from 30%/52% for IPI of 1-2 to 12%/14% for IPI 4-5. The prognostic index for T-cell lymphoma (PIT) was more effective at identifying a lower risk group: 5-y TTP/ OS (PIT 1 40%/57%; PIT 2 21%/28%; PIT 3 21%/20% PIT 4 9%/10%, p = 0.002/0.001). Both models were prognostic in PTCL-NOS and TFHTCL. (Table 1) Conclusion With mature follow-up, ~ 30% of all older pts treated with curative intent CHOP-like chemotherapy remain progression-free and are alive at 5 y. Although results remain suboptimal, robust older patients can still be considered for curative intent CHOP chemotherapy with tailored doses to mitigate toxicity. Those with low risk IPI/PIT scores have a more favourable outcome with this approach, with a 5-y OS of > 50%, suggesting a benefit of subsequent therapies. In contrast, higher risk disease have poor outcomes and novel therapeutic approaches should be considered. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical Factors Impact on Pharmacokinetics of CT-P10 and Reference Rituximab in Patients with Advanced-Stage Follicular Lymphoma

Background: CT-P10 is the first biosimilar to the innovator rituximab (RTX), which was approved by the European Medicines Agency for all indications for which RTX is approved. Pharmacokinetic equivalence and comparable efficacy was demonstrated in advanced-stage follicular lymphoma patients (Kim WS et al. Lancet Haematol. 2017; S2352-3026(17)) as well as in rheumatoid arthritis (Yoo DH, et al. Arthritis Rheumatol. 2016; 68 (suppl 10)). It is known that there are several factors affecting on pharmacokinetics (PK) of rituximab. However, there are limited data on comparing PK data between a biosimilar of rituximab and RTX with different subgroups in advanced-stage follicular lymphoma (AFL) patients.Objective: This report is to investigate the PK of CT-P10 according to the several relevant clinical factors and to compare with RTX in the post-hoc analysis of randomized controlled trial to compare CT-P10 and RTX in advanced-stage follicular lymphoma (NCT02162771).Methods: A total of 121 patients of PK population were included in this analysis. Fifty nine patients in the CT-P10 group and 62 patients in the RTX group received CT-P10 or RTX (375 mg/m2 i.v) plus CVP (cyclophosphamide, vincristine and prednisone) for every 3 weeks over 8 cycles. Area Under the Concentration-time curve at steady state (AUCtau) and the maximum serum concentration at steady state (CmaxSS) at Cycle 4 and trough serum concentration (Ctrough) at Cycle 4 and Cycle 8 were calculated by standard non-compartmental methods using Phoenix WinNonlin. The parameters were analysed by subgroups of Gender (male vs. female), Eastern Cooperative Oncology Group (ECOG) Performance Status (0 vs. ≥1), Follicular Lymphoma International Prognostic Index (FLIPI) Score (0-2 vs. 3-5) and its component (Age (≥60 vs. <60), Hemoglobin [Hb] (≥120g/L vs. <120g/L), Lactate dehydrogenase [LDH] (>UNL vs. ≤UNL), number of nodal sites (>4 vs. ≤4)), presence of bulky lesion at baseline (≥7cm vs. <7cm) and Complete response (CR)/Complete response unconfirmed (CRu) as best overall response assessed by International Working Group 1999 in the each and combined group of CT-P10 and RTX. Outliers which determined by robust regression outlier testing were excluded in this analysis. For AUCtau, 7 patients (5 in the CT-P10 group and 2 in the RTX group) and among them, 4 patients (2 patients in each group) for CmaxSS were defined as outliers.Result: Higher AUCtau and CmaxSS were observed in patients who are female, under 60 years old, good ECOG Performance Status, low FLIPI score, normal Hb and LDH levels, and non-bulky disease at baseline as shown in Table 1. In patients who achieved CR/CRu as their best overall response during 8 cycles showed higher AUCtau, CmaxSS and Ctrough than in patients who did not achieve CR/CRu response in both CT-P10 and RTX groups. At Cycle 4 and Cycle 8, mean Ctrough in the CR/CRu responder were 72 μg/mL, 108 μg/mL, respectively, and those concentrations are 56 μg/mL, 96 μg/mL in the CR/CRu non-responder. Importantly, there was no statistically significant difference between the CT-P10 and RTX in any of subgroup analyses; confidence interval of the ratio of geometric mean of CT-P10 to RTX contains 1 using Satterthwaite approximation for each comparison.Conclusion: Female gender, younger age (<60), better ECOG Performance Status, lower FLIPI score, LDH and Hb levels in normal range, absence of bulky disease at baseline and better response are factors associated with increased serum rituximab concentration in the combined treatment groups. No statistically significant differences were found between CT-P10 and RTX groups in PK at all subgroup analyses. Therefore, this result shows that the PK of CT-P10 is in accordance with the RTX from historical data and further supports the PK similarity between CT-P10 and RTX. [Display omitted] DisclosuresKim:Celltrion, Inc: Consultancy, Honoraria; Roche: Research Funding; Mundipharma: Research Funding; Novartis: Research Funding; Kyowa-Kirin: Research Funding; Donga: Research Funding; J&J: Research Funding; Takeda: Research Funding. Coiffier:Celltrion, Inc: Consultancy, Honoraria. Buske:Hexal: Honoraria; Celltrion, Inc.: Consultancy, Honoraria; Pfizer: Honoraria; Gilead: Honoraria; Janssen: Honoraria, Research Funding; Roche: Honoraria, Research Funding. Ogura:SymBio: Consultancy, Research Funding; Celgene: Consultancy, Honoraria; Astrazeneca: Honoraria; Takeda: Consultancy, Honoraria; Mundipharma: Consultancy; MeijiSeika Pharma: Consultancy; Celltrion, Inc: Consultancy, Honoraria. Kwak:Celltrion, Inc: Consultancy; InnoLifes: Consultancy, Equity Ownership; Pepromene Bio: Consultancy, Equity Ownership. Lee:Celltrion, Inc: Employment. Bae:Celltrion, Inc: Employment. Kim:Celltrion, Inc: Employment. Kim:Celltrion, Inc: Employment. Lee:Celltrion, Inc: Employment. Kwak:Celltrion, Inc: Employment. Lee:Celltrion, Inc: Employment.

Clinical Features and Treatment Approaches in Patients with Rosai-Dorfman Disease: The Mayo Clinic Experience

IntroductionRosai-Dorfman disease (RDD) is a rare subtype of non-Langerhans cell histiocytosis that is classically characterized by lymphadenopathy and accumulation of CD68-positive, S100-positive, and CD1a-negative histiocytes with frequent emperipolesis in sinuses of lymph nodes and lymphatics of internal organs. In this series, we report on the clinical features, treatment strategies utilized and outcomes of a large cohort of RDD patients seen at one institution.MethodsWe retrospectively reviewed the medical records of patients with biopsy-proven RDD evaluated at the Mayo Clinic from January 1, 1994 to September 2, 2016. Data abstracted from the medical records included: demographic characteristics, symptoms at disease presentation, treatment, and outcomes. In addition, radiologic and molecular findings were collected when available.ResultsA total of 55 patients with confirmed RDD were included in our study. The median age at diagnosis was 50 years (range, 2-79), including 4 pediatric subjects. The median duration from symptom onset to diagnosis was 6.4 months (range, 0-128; mean 18 months). There was a female preponderance (male 1: female 1.5). The most common presenting signs and symptoms were painful or painless subcutaneous masses (40%), lymphadenopathy (13%), bone pain (11%), constitutional symptoms (fevers, chills, myalgia, or weight loss: 11%), and abdominal pain (11%). The organ systems involved with RDD based on either histopathological or radiological findings are shown in the Table. In our series, extranodal presentation in the soft tissue (55%) was more common than a nodal presentation (38%). Other rare extranodal sites included one case each involving the parotid gland, thyroid gland, testicles, and rectum. The median number of biopsies required to establish diagnosis was 2 (range, 1-6). Next generation sequencing was performed on 2 patient samples, and showed a CDC73 truncation in exon 5 in the first case and a KRAS K117N mutation in the second case. BRAF V600E mutation testing was negative in 2 patients: one by immunohistochemistry and one by urine cell-free DNA PCR.Treatment data were available for 46 patients. Of these, 13% patients were observed. The most common first line therapeutic modalities used were surgical excision (39%) and corticosteroids (35%). Other first-line systemic therapies included rituximab in 2 patients and vinblastine in 1 patient. Approximately 13 (28%) patients developed recurrent disease and were treated with other modalities: surgery (n=4), radiation therapy (n=3), and systemic therapies like cladribine (n=4), CVP (cyclophosphamide, vincristine, and prednisone; n=1), and 6-mercaptopurine with prednisone (n=1).The median duration of follow-up after diagnosis was 20 months (range, 0-188). At the time of last follow-up, 4 patients were deceased. Of the deceased, 3 patients died from other malignancies (acute myeloid leukemia, peripheral T-cell lymphoma, and metastatic gall bladder carcinoma) and the cause of death for 1 patient was unknown.ConclusionsRDD is a rare histiocytic disorder presenting with diverse clinical manifestations. The diagnosis is often delayed due to inconclusive biopsies, and in some instances, multiple biopsy attempts are necessary to secure a definitive diagnosis. Approximately one-third of patients may require second-line systemic therapies. Next generation sequencing might yield targetable mutations in RDD patients that relapse or have progressive multi-organ disease. [Display omitted] DisclosuresNowakowski:Morphosys: Consultancy, Research Funding; celgene: Consultancy, Research Funding; Genetech: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; pharmacyclics: Consultancy; Abbvie: Consultancy; Nanostring: Research Funding. Sher:LAM Therapeutics, Inc: Research Funding. Parikh:Pharmacyclics: Honoraria; Pharmacyclics: Research Funding; AstraZeneca: Honoraria.

PB1902 THE BARCELONA‐BRNO BIOMARKERS‐ONLY PROGNOSTIC MODEL FOR CHRONIC LYMPHOCYTIC LEUKEMIA ‐ SINGLE CENTRE EXPERIENCE

Background:The Barcelona‐Brno biomarkers‐only chronic lymphocytic leukemia (CLL) prognostic model is a new, simplified version of the International Prognostic Index for Chronic Lymphocytic Leukemia (CLL –IPI), developed for outcome prediction on the basis of the two most important prognostic markers in CLL, mutational status of immunoglobulin heavy variable (IGHV) genes and cytogenetic abnormalities detected by fluorescent in situ hybridization (FISH).Aims:The aim of this study was to evaluate the prognostic power of the biomarkers‐only CLL prognostic model in a cohort of Serbian CLL patients.Methods:This retrospective study enrolled a total of 133 unselected CLL patients, which were diagnosed, managed and followed in Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia. All patient data (clinical and laboratory parameters at diagnosis, FISH cytogenetics performed prior to first therapy and IGHV mutational status) were collected from patients’ medical records and patients were stratified according to the biomarkers‐only CLL prognostic model. Comparison of overall survival (OS) and time to first treatment (TTFT) between risk groups was conducted using the Kaplan‐Meier method and log‐rank test.Results:The median age at diagnosis was 59 years (range 30–88). Male to female ratio was 1.96. Forty‐four percent of patients were diagnosed with Binet stage A, 38% with Binet B, and 18% with Binet C. Regarding IGHV mutational status, 59 patients (44.4%) were mutated, and 74 patients (55.6%) were unmutated. Normal karyotype, del(13q), del(11q), trisomy(12), and del(17p) were detected by FISH in 48.1%, 29.3%, 10.5%, 7.5%, and 4.5% of patients, respectively. According to the biomarkers‐only prognostic model, 54 patients (40.6%) were assigned as low risk, 65 (48.9%) as intermediate risk and 14 (10.5%) as high risk. During the median follow‐up of 9 years, 42.9% of patients died and 81.2% received treatment. Patients were treated in the first line as follows: 80 (74%) with fludarabine‐based therapy (61% FC, 39% FCR), 8 (7%) with cyclophosphamide, vincristine and prednisone (COP), 15 (16%) with chlorambucil, and 3 patients (3%) with other treatment options.The median TTFT in our cohort was 55 months (95%CI 0–125 months). Patients in low risk group had significantly longer median TTFT (168 months) in comparison to patients in intermediate (29 months) and high (38 months) risk groups (Log rank test across groups p &lt; 0.001)(Figure 1A). However, the difference in median TTFT between the latter two risk groups was not significant. In our cohort median OS was 108 months (95%CI 78‐138 months). Similarly to TTFT, median OS in low risk group was significantly longer (not reached) in comparison to median OS in intermediate and high‐risk groups (82 and 94 months, respectively)(Log rank test across groups p &lt; 0.001)(Figure 1B). Again, no significant difference in OS between intermediate and high risk groups was observed.The biomarkers‐only model was also shown to be a good predictor of TTFT and OS in patients younger than 65 years (p &lt; 0,001), but not in older patients (≥65 years). In addition, the model successfully stratified patients within Binet A and B group regarding both TTFT (p = 0.003 and p = 0.007, respectively) and OS (p = 0.018 and p = 0.009, respectively), while it was not relevant in the Binet C group.Summary/Conclusion:The Barcelona‐Brno biomarkers‐only CLL prognostic model is an effective prognostic marker in Serbian CLL patients regarding both TTFT and OS, especially in younger patients and Binet A or B patients with low risk disease.image

Evaluation of Different Treatment Regimens for Relapsed and Refractory NHL: Single Institute Experience

Background and Aim: The treatment of choice for relapsed or refractory Non-Hodgkin Lymphoma (NHL) mainly, is High dose chemotherapy with autologous stem cell transplantation. However, its use is mostly restricted to patients responding to salvage chemotherapy. In this study, our aim was to evaluate outcome and toxicity of different treatment modalities of relapsed and refractory NHL. Patient and Methods: This retrospective study included 217 patients were diagnosed as refractory or relapsed NHL. Those patients received different treatment modalities as GDP (Gemcitabine, dexamethasone, cisplatin), DHAP (Dexamethasone, Cytarabine, and Cisplatin), MINE (Mitoxantrone, ifosfamide, etoposide and mesna), CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisone), and CVP (Cyclophosphamide, vincristine and prednisone). Results: The median age of patients in the study was 50 years. Patients who received DHAP showed ORR of 62%, which was the highest response. The most common adverse effects were hematological which were more noticed in patients, received CHOP. Sixty one patients (54.5%) had anemia, 54 patients (48.2%) had neutropenia and 55 patients (49.1%) had thrombocytopenia, but the difference between the different lines of treatment wasn’t significant p value of 0.95. The median time to relapse is 10 months and the median survival time is 40 months. The 3-year PFS rates of all patients were 49.3%, while the 3 year OS rates were 54.8%. Conclusion: The overall and PFS didn’t show any difference between different lines of treatment.

Comparison of Efficacy and Safety of Biosimilar CT-P10 to Rituximab in Patients with Previously Untreated Low Tumor Burden Follicular Lymphoma (LTBFL): A Randomized Phase III Study

Background: CT-P10 is the first biosimilar to innovator rituximab (RTX) approved for all indications by the European Medicines Agency. The pharmacokinetics (PK) equivalence and non-inferior efficacy of CT-P10 compared with RTX in patients with newly diagnosed advanced follicular lymphoma (FL) was previously demonstrated when used with combination chemotherapy of cyclophosphamide, vincristine and prednisone (CVP) (Kim WS et al,. 2017).Objectives: This is an ongoing, phase 3, randomized, double blind, active controlled study to demonstrate similarity of efficacy and safety between CT-P10 and RTX as monotherapy in patients with newly diagnosed FL with low tumor burden (NCT02260804). The results of efficacy as determined by overall response rate (ORR), PK, pharmacodynamic, safety and immunogenicity up to 7 months (prior to Maintenance Cycle 3) are presented here.Methods: Patients with FL with stage II-IV, Grade 1-3a and low tumor burden as assessed by GELF criteria were randomized in a 1:1 ratio to receive either CT-P10 or RTX (375mg/m2 i.v.) monotherapy weekly for 4 weeks as induction therapy, followed by maintenance therapy every 2 months for 2 years. Patients who had complete response (CR), unconfirmed CR, partial response or stable disease after the induction therapy were eligible for maintenance therapy. The primary endpoint was ORR over 7 months according to the IWG criteria and was assessed by the independent review committee as central review and by the site investigator as local review.Results: In total, 258 patients were randomized to either the CT-P10 (n=130) or RTX (n=128) group with well-balanced baseline characteristics. Overall, 231 patients (n=119/130 [92%] and n=112/128 [88%] in the CT-P10 and rituximab groups, respectively) completed up to 7 months. Therapeutic similarity between CT-P10 and RTX was established by meeting the predefined margin of ±17% for the primary efficacy endpoint of ORR in the intent-to-treat (ITT) and per-protocol (PP) population (Figure 1). An ORR of 83.1% and 81.3% for CT-P10 and RTX, respectively, was observed over 7 months. The ORR difference was 1.8% and 90% confidence interval (CI) of the treatment difference estimate was entirely within the equivalence margin; 90% CI (-6.43, 10.20).Similar PK profiles were shown in the CT-P10 and RTX. Maximum and trough concentration of CT-P10 or RTX at each cycle were similar between the two groups. Median number of B-cells decreased to the lower limit of quantification (<20cells/μL) after the 1st infusion and remained as depleted over 7 months in both groups.CT-P10 was well tolerated and the safety profile of CT-P10 over 7 months was consistent with that of RTX, with no new, unexpected safety findings. Treatment-emergent adverse events (TEAEs) were reported in 71% and 67% patients in the CT-P10 and RTX, respectively. Adverse events of special interest included infections and infusion-related reactions occurred in a similar proportion of patients in each treatment group (Table 1). Neither progressive multifocal leukoencephalopathy nor Hepatitis B virus reactivation was reported in either group. The proportion of patients with positive anti-drug antibody were similar between 2 groups (0.8% vs. 2.3%) over 7 months. Among them, neutralizing antibody were detected in one patient in the CT-P10 group.Conclusions: This study demonstrates therapeutic equivalence of CT-P10 to RTX in previously untreated LTBFL. CT-P10 was well-tolerated and the safety profile including immunogenicity of CT P10 was comparable to that of RTX over 7 months. [Display omitted] DisclosuresOgura:SymBio: Research Funding; Mundi Pharma: Consultancy; Celltrion: Consultancy, Research Funding; Takeda: Honoraria; Cellgene: Honoraria; MeijiSeika Pharma: Consultancy. Sancho:SERVIER: Honoraria; SANOFI: Honoraria; CELGENE: Honoraria; KERN FHARMA: Honoraria, Speakers Bureau; GILEAD: Honoraria, Research Funding; JANSSEN: Honoraria, Speakers Bureau; ROCHE: Honoraria, Speakers Bureau; MUNDIPHARMA: Honoraria. Lennard:Janssen: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Research Funding. Jurczak:European Medicines Agency: Consultancy; Astra Zeneca/Acerta: Consultancy, Research Funding; Sandoz-Novartis: Consultancy; Janssen: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Afimed: Research Funding; Bayer: Research Funding; Beigene: Research Funding; Celgene: Research Funding; Epizyme: Research Funding; Nordic Nanovector: Research Funding; Merck: Research Funding; Morphosys: Research Funding; Pharmacyclics: Research Funding; Servier: Research Funding; Roche: Research Funding; TG Therapeutics: Research Funding. Coiffier:CELGENE: Consultancy, Membership on an entity's Board of Directors or advisory committees; MUNDIPHARMA: Membership on an entity's Board of Directors or advisory committees; CELLTRION: Membership on an entity's Board of Directors or advisory committees; MORPHOSYS: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Membership on an entity's Board of Directors or advisory committees. Buske:Roche: Honoraria, Research Funding; Bayer: Research Funding; Janssen: Honoraria, Research Funding. Lee:Celltrion, Inc: Employment.

Abstract 305: Cerdulatinib induces Bim expression and synergistic cell kill in combination with venetoclax in follicular lymphoma cell lines

Abstract Follicular lymphoma (FL) is the most frequently occurring indolent B-cell non-Hodgkin lymphoma. Treatment typically involves rituximab in combination with bendamustine, CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), or CVP (cyclophosphamide, vincristine, and prednisone). Disease relapse is high, and current treatment options for these patients are limited. BTK inhibition has limited clinical activity in FL patients, and while the PI3Kδ inhibitor idelalisib was recently approved, tolerability has been an issue. Limited clinical activity was observed with the Bcl-2 inhibitor venetoclax, due to a compensatory upregulation of Mcl-1 by the tumor cell. Consequently, novel treatment strategies are required for patients with relapsed/refractory FL. Cerdulatinib is a dual SYK/JAK inhibitor that targets the BCR and cytokine signaling pathways. We previously demonstrated in chronic lymphocytic leukemia (CLL) cells that cerdulatinib inhibited signaling via the BCR and IL-4 signaling pathways and induced apoptosis in a dose- and time-dependent manner. However, the mechanism behind cerdulatinib-induced tumor killing has not previously been investigated. Herein we explore the function of cerdulatinib alone and in combination with venetoclax for the treatment of FL. To confirm cerdulatinib activity in FL derived cells lines WSU-FSCCL, DOHH2 and SU-DHL6, cells were incubated with cerdulatinib prior to BCR or cytokine receptor engagement. Cerdulatinib (0.1-1µM) significantly inhibited anti-Ig-induced pAKTS473, pERKThr202/Tyr204, pS6 ribosomal subunit Ser235/236 and cytokine-induced STAT signaling. The Bcl-2 protein was highly expressed in all cell lines consistent with a t(14:18) translocation, whereas basal Mcl-1 was expressed at lower levels. Bcl-2 levels remained unchanged following cerdulatinib treatment in all three cell lines. However, in contrast to CLL where cerdulatinib inhibited Mcl-1 expression, modulation of Mcl-1 protein expression by cerdulatinib in FL cell lines was subtle and inconsistent. Cerdulatinib alone induced 12%-44% cell death in all cell lines tested in a time dependent manner (24-72h) and this correlated with a robust increase in Bim expression at the RNA and protein level. We subsequently treated DOHH2, WSU-FSCCL and DHL6 cells with cerdulatinib in combination with 10-100nM venetoclax. Venetoclax synergized with cerdulatinib to induce significantly greater levels of apoptosis in all cell lines investigated compared to either agent alone and appeared to function by displacing Bim from Bcl-2. To demonstrate in vivo capability, we xenografted SU-DHL6 subcutaneously in nude mice. Cerdulatinib in combination with venetoclax led to greater antitumor activity when compared to vehicle or either drug alone. Together these data highlight a rationale for combining cerdulatinib with venetoclax for the treatment of FL. Citation Format: Andrew J. Steele, Greg Coffey, JiaJia Feng, Matthew D. Blunt, Francis DeGuzman, Deogracias Canivel, Jack Rose, Kenneth Der, Janet Leeds, Anjali Pandey, Pamela Conley. Cerdulatinib induces Bim expression and synergistic cell kill in combination with venetoclax in follicular lymphoma cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 305.

Double-blind, randomized phase 3 study to compare efficacy and safety of the biosimilar CT-P10 to rituximab combined with CVP therapy in patients with previously untreated advanced-stage follicular lymphoma.

7532 Background: CT-P10 is a biosimilar candidate to the innovator rituximab (RTX). In patients with rheumatoid arthritis, CT-P10 has demonstrated equivalence in pharmacokinetics (PK) and efficacy (Yoo, ACR 2016). This study aimed to demonstrate non-inferiority of efficacy and PK equivalence between CT-P10 and RTX in patients with newly diagnosed advanced follicular lymphoma (AFL) (NCT02162771). PK equivalence was confirmed (Coiffier, ASH 2016). Methods: A total of 140 patients were randomized in a 1:1 ratio to receive CT-P10 or RTX (375 mg/m2 i.v) plus CVP (cyclophosphamide, vincristine, and prednisone) every 3 weeks over 8 cycles. Overall response rate (ORR) according to the 1999 IWG criteria over 24 weeks was assessed by the independent review committee. Results: Noninferiority of CT-P10 to RTX was shown for the primary efficacy endpoint of ORR. The ORR difference was 4.3% (Table) and the lower bound of the 95% confidence interval was -4.25%. B-cell depleted after the 1st infusion and remained as depleted over 8 cycles in both groups. Overall safety profile of CT-P10 was consistent with that of RTX and the proportion of patients with positive anti-drug antibody was similar in both groups (4.3% and 2.9%) for 24 weeks. Neither progressive multifocal leukoencephalopathy nor Hepatitis B virus reactivation was reported in each group. Conclusions: This study demonstrates noninferiority of efficacy of CT-P10 to RTX combined with CVP in previously untreated AFL. CT-P10 was well-tolerated and the safety profile including immunogenicity of CT-P10 was comparable to that of RTX over 8 cycles of induction period. Clinical trial information: NCT02162771. [Table: see text]

Longer Term Efficacy and Safety of Subcutaneous Compared with Intravenous Rituximab: Updated Results of the Phase 3 SABRINA Study

Longer Term Efficacy and Safety of Subcutaneous Compared with Intravenous Rituximab: Updated Results of the Phase 3 SABRINA Study

Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Treatment-Related Weight Change and Overall Survival in United States Veterans with Follicular Lymphoma

IntroductionWeight loss during chemotherapy has been associated with decreased overall survival (OS) in various solid tumors. While weight loss >10% in the 6 months leading up to diagnosis is a known adverse prognostic factor for non-Hodgkin's lymphoma (one of the B symptoms), the association between weight loss during chemotherapy and survival in follicular lymphoma (FL) patients is not well understood. Few studies have looked at long-term weight change patterns following chemotherapy treatment in this patient population. We investigated short and long-term weight change trends, predictors, and association with OS and disease-specific survival (DSS) in a cohort of FL patients.MethodsFL patients diagnosed and treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) +/- rituximab, CVP (cyclophosphamide, vincristine, and prednisone) +/- rituximab, or rituximab monotherapy regimens between 1998 and 2010 were identified in the Veterans Health Administration database. Data on weight 1 year prior to treatment, at time of first treatment (baseline), and up to 5 years after treatment initiation was obtained. Additional data on height, age, stage, race, comorbidities, date of diagnosis, LDH, and B-symptoms was obtained. Body Mass Index (BMI) at diagnosis was categorized according to World Health Organization criteria. Weight change during treatment is calculated as difference between baseline weight and 3 months after start of treatment. Long-term weight change is calculated as difference between baseline weight and 24 months after start of treatment. Logistic regression identified factors associated with long-term weight gain. Landmark Cox analysis evaluated prognostic significance of weight loss during treatment among patients who survived at least 6 months after treatment initiation.Results1022 patients met inclusion criteria out of 2235. Mean and median age at diagnosis was 63.6 and 63.0 years respectively, 95.9% were men, and 72.7% had Stage III/IV disease. The mean Charlson co-morbidity score was 2.3. B symptoms were present in 37.9% and LDH was elevated in 26.8%.Mean and median weight change during treatment was -1.4kg (-1.5%) and -0.4kg (-0.6%), with a majority of patients losing weight (56%) and 23% of patients losing >5% of their baseline weight. In contrast, mean and median weight change at 24 months after treatment initiation was +1.2kg (+1.6%) and +1.3kg (+1.6%), with a majority of patients (57%) gaining weight and 14% of patients gaining >10% of their baseline weight after treatment completion.Logistic regression analysis identified factors associated with increased risk of weight gain >10% at 24 months after treatment initiation. These included: weight loss >5% in the year prior to treatment (Odds Ratio (OR) 6.82, 95% Confidence Interval (CI) 3.09-15.05), weight gain between 0-5% during treatment (OR 2.53, 95% CI 1.21-5.27), and weight gain >5% during treatment (OR 9.43, 95% CI 3.85-23.14).Kaplan-Meier survival analysis showed that weight loss >5% during treatment was associated with decreased OS (p<0.0001) and disease specific survival (DSS) (p=0.0027) compared to weight loss <5% or weight gain. A landmark Cox analysis controlling for age, disease stage, comorbidities, elevated LDH, B symptoms, BMI at diagnosis, and treatment type showed that weight loss >5% during treatment was independently associated with worse OS (Hazard Ratio (HR) 1.71, 95% CI 1.32-2.22) and DSS (HR 1.61, 95% CI 1.11-2.34).ConclusionsIn patients with FL, weight loss >5% during treatment is independently predictive of worse overall survival and disease-specific survival. Weight loss could be considered in conjunction with other dynamic variables (such as PET positivity and nodal size) to assess prognosis at the end of therapy. 14% of patients experience long-term weight gain >10% of baseline. Patients who gained 5% or more during treatment are at highest risk (OR=9.4) for long-term weight gain-this subset of patients could be targeted for weight loss interventions to prevent future obesity-related comorbidities. DisclosuresNo relevant conflicts of interest to declare.

Successful treatment of a Caucasian case of multifocal Castleman’s disease with TAFRO syndrome with a pathophysiology targeted therapy - a case report

BackgroundCastleman-Kojima disease (TAFRO Syndrome) is characterized by Thrombocytopenia, Anasarca, myeloFibrosis, Renal dysfunction, Organomegaly, multiple lymphadenopathy and histopathology pattern of atypical Castleman’s disease (CD). Only few cases of this recently identified unique variant of Multicentric CD (MCD) are described in literature, all Japanese. It therefore poses serious diagnostic and therapeutic challenges.Case descriptionWe describe a 21 year old woman with fever, asthenia, bilateral pleural effusion, ascites, hypoalbuminemia, severe thrombocytopenia, anemia, renal failure and proteinuria, whereas microbiological tests, immune serology (except ANA) and bone marrow biopsy were all negative. A CT-scan showed multiple lymphadenopathy and tissue samplings of mediastinal lymph nodes was compatible with a mixed-type CD. The diagnosis of MCD with TAFRO syndrome was made, but after an initial improvement with high dose corticosteroid therapy, clinical and laboratory features worsened. Based upon the high serum IL-6 levels and the high number of CD20-lymphocytes in lymph nodes tissue, we started tocilizumab (partial benefit), followed by rituximab combined with CVP (cyclophosphamide, vincristine and prednisone) chemotherapy, achieving a complete response. A total of six cycles of R-CVP were administered monthly, followed by maintenance with monthly rituximab. A complete remission persists at the 12th month of follow-up.ConclusionsIn patients with massive immune system activation and lymphadenopathy it is mandatory to rule out Castleman-Kojima disease. In our patient a therapy aimed at the prominent pathophysiological abnormalities has been successful so far. However, since the rarity of TAFRO Syndrome, a multicenter registry is strongly desirable for a better understanding of the disease mechanisms, hopefully leading to evidence-based therapeutic choices.

Incidence of pneumonitis in patients with non-Hodgkin lymphoma receiving chemoimmunotherapy with rituximab

Rituximab is a monoclonal anti-CD20 antibody that is standard of care for treatment of B-cell non-Hodgkin lymphoma (NHL). The purpose of this study was to quantify the incidence of rituximab (R)-related interstitial pneumonitis (IP) in patients with NHL receiving immunochemotherapy. All patients with NHL who received cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), cyclophosphamide, vincristine and prednisone (CVP), R-CHOP or R-CVP in Princess Margaret Hospital between June 1998 and August 2009 were retrospectively reviewed. We compared cohorts of patients who did and did not receive R and documented the incidence of IP during and/or post-treatment. In total 560 patients were included in this analysis. The rate of IP in the entire cohort was 2.9% (16/560) with a trend toward a higher rate in the R group (3.95% vs. 1.3% [odds ratio 3.1, 0.84–17.27, p = 0.074]). Baseline pulmonary computed tomography abnormalities in patients with lymphoma are relatively common. The addition of R to chemotherapy does not significantly increase the risk of symptomatic chemotherapy-related IP.

Treatment-Related Weight Change In United States Veterans With Non-Hodgkin Lymphoma

▪ IntroductionPrior studies have demonstrated weight gain among recipients of chemotherapy for various solid tumors, though there is little evidence describing weight changes during and after treatment in patients with non-Hodgkin lymphoma (NHL). Weight gain during and after treatment can contribute to an increased risk of chronic conditions including: diabetes, coronary disease, and hypertension. This is important for long-term health in patients with diseases that are potentially curable or associated with long-disease free intervals, such as diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). We investigated the magnitude of weight change during and after treatment in a cohort of DLBCL and FL patients. MethodsDLBCL and FL patients diagnosed between 1998 and 2008 and treated with combination chemotherapy +/- rituximab, were identified in the Veterans Health Administration database. Data on weight at time of first treatment (baseline) and at all recorded weight measurements up to 5 years after treatment initiation was obtained. Additional data included: height, age, race, co-morbidities, date of diagnosis, disease stage, LDH at diagnosis, B-symptoms, and treatment details (drugs, dates, and dosages). Only patients treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) +/- rituximab or CVP (cyclophosphamide, vincristine, and prednisone) +/- rituximab were included in the study cohort. Patients were categorized as gaining or losing 0-2.5%, 2.5-5%, 5-7.5%, 7.5-10%, or >10% of baseline weight. Weight change during treatment was calculated utilizing baseline and weight measurement at or near 3 months following treatment initiation. B-spline modeling was applied to further evaluate trends in weight change over time within the cohort. Results2,159 patients met inclusion criteria. Mean age at diagnosis was 63.1 years, 96.6% of patients were men, and 59.5% of patients had stage III/IV disease. Mean Charlson co-morbidity score was 2.2. B-symptoms were noted at diagnosis in 48.4% of patients and LDH was elevated in 47.2% of patients. Mean and median weight change at 3 months after treatment initiation were -1.9 kg and -1.1 kg respectively, or -2.1% and -1.3% of baseline weight. Figure 1 illustrates the distribution of weight change during treatment within the cohort. In B-spline analysis, weight loss was maximal at 4.14 months after first treatment, with subsequent weight gain until reaching a plateau at 22 months (Figure 2). Among patients with 24 months or more of follow-up data, 45.7% had gained weight at 3 months and 60.5% had gained weight at 24 months. Only 4.3% of patients had gained >10% of baseline weight at 3 months, while 23.0% had gained >10% at 24 months. Similarly, 15.4% of patients had gained >5% of baseline weight at 3 months, while 38.5% had gained >5% at 24 months. Of the patients that gained weight at 3 months, 9.3% had gained >10% of baseline weight, while of the patients that gained weight at 24 months, 38.0% had gained >10%. Patients who gained weight in the first 3 months after treatment initiation were more likely to gain >10% baseline weight at 24 months compared to those who lost weight in the first 3 months. [Display omitted] [Display omitted] DiscussionThese results suggest that in contrast to other malignancies, most patients with NHL who are treated with multi-agent chemotherapy actually experience weight loss rather than weight gain over the course of treatment. Despite this initial trend, a majority of these patients undergo significant weight gain after the conclusion of therapy and in subsequent months. This poses a long-term health risk, particularly to patients who achieve a complete remission and long-term disease control. The timing of greatest weight gain in the 6-18 months after treatment initiation suggests an opportune time for initiation of a diet or exercise intervention to reduce weight gain shortly after the end of treatment. Disclosures:No relevant conflicts of interest to declare.

Outcome and pathologic classification of children and adolescents with mediastinal large B-cell lymphoma treated with FAB/LMB96 mature B-NHL therapy

AbstractMediastinal large B-cell lymphoma (MLBL) represents 2% of mature B-cell non-Hodgkin lymphoma in patients ≤ 18 years of age. We analyzed data from childhood and adolescent patients with stage III MLBL (n = 42) and non-MLBL DLBCL (n = 69) treated with Group B therapy in the French-American-British/Lymphome Malins de Burkitt (FAB/LMB) 96 study. MLBL patients had a male/female 26/16; median age, 15.7 years (range, 12.5-19.7); and LDH < 2 versus ≥ 2 × the upper limit of normal, 23:19. Six MLBL patients (14%) had < a 20% response to initial COP (cyclophosphamide, vincristine, and prednisone) therapy. Central pathology revealed approximately 50% with classical features of primary MLBL. Five-year event-free survival for the stage III MLBL and non-MLBL DLBCL groups was 66% (95% confidence interval [CI], 49%-78%) and 85% (95% CI, 71%-92%), respectively (P < .001; 14%). The 5-year overall survival in the 42 MLBL patients was 73% (95% CI, 56%-84%). We conclude that MLBL in adolescent patients is associated with significantly inferior event-free survival compared with stage III non-MLBL DLBCL and can be of multiple histologies. Alternate treatment strategies should be investigated in the future taking into account both adult MLBL approaches and more recent biologic findings in adult MLBL.

Differences in Outcomes in Males and Females with Diffuse Large B-Cell Lymphoma with Induction Rituximab and Follicular Lymphoma Treated with Maintenance Rituximab

AbstractAbstract 3705Improved outcomes were reported in USA studies in DLBCL (Habermann et al. J Clin Oncol 2006) in a two-staged randomized study of R-CHOP (rituximab, cyclophosphamide, Adriamycin, vincristine, and prednisone) versus CHOP with a second randomization assignment to maintenance rituximab (MR) or observation (OBS) (E4494) and in follicular lymphoma (FL) in patients in a trial with CVP (cyclophosphamide, vincristine, and prednisone) followed by randomization to MR versus OBS in advanced-stage indolent lymphoma (E1496) (Hochster et al. J Clin Oncol 2009). The details of the treatment regimens have been previously described. The German High Grade Lymphoma Study Group has reported differences between men and women in outcomes in DLBCL with improved outcomes in women treated with rituximab (Müller et al. Blood 2012). Methods:Survival outcomes by sex were analyzed using a stratified weighted cox regression, removing the effect of maintenance rituximab in DLBCL (E4494), and a log-rank test in patients with follicular histology (E1496). A Cox regression model was used to evaluate the differences between males and females together with weight (below or above the median). Wilcoxon test and Fisher's exact test were used to compare medians and proportions, respectively. Results:In DLBCL, there were 273 eligible males and 273 females. The median age was 69 in males and 70 in females. There were no differences in baseline patient characteristics among the male and female populations. 138 males and 129 females were treated with R-CHOP. There was no difference in treatment received, with 83% females and 75.3% males receiving 6 cycles or more of R-CHOP treatment (p=0.14). The complete remission (CR) and partial remission (PR) rates after RCHOP were higher in females (82.6%) versus males (71.5%) (P = 0.04). With a median follow-up of 9.45 years, the failure free survival (FFS) and overall survival (OS) were improved in females (P = 0.02, 0.002; HR=0.63, 0.54) compared with males in the R-CHOP group. The outcomes were not different in the CHOP group for FFS (P = 0.81) or OS (P= 0.57) between males and females. Within the R-CHOP group, the failure free survival (FFS) was significantly different between women and men (P = 0.002) and body weight (P = 0.03), but only female sex (P = 0.001) was significant and not weight (P = 0.26) for OS. Of 282 evaluable patients with advanced-stage follicular lymphoma who received initial treatment with CVP, 115 patients were randomly assigned to MR and 113 to OBS. 120 patients were male, and 108 were female. The median age was 58 years in the MR arm and 54 years in the OBS arm. At a median follow-up of 8.04 years, MR markedly improved the PFS (P=0.003) compared with OBS. There were no differences in PFS (P= 0.17) between males and females treated with MR or OS (P = 0.27). In conclusion, in induction therapy with rituximab in DLBCL there is a sex dependent effect with rituximab with males benefiting less than females. In contrast, in patients with follicular lymphoma treated with chemotherapy followed by maintenance rituximab, there were no differences. The differences in outcomes in patients of different sex with DLBCL treated with immunochemotherapy and FL treated with maintenance rituximab will require further analysis of multiple clinical and biologic variables. Disclosures:Fisher:Roche: Advisory Board Other. Cheson:Genentech: Consultancy. Kahl:Genentech, Roche: Consultancy, Research Funding. Horning:Genetech, Roche: Employment, stock (Roche) Other.

Quantitative Proteomics Reveals that miR-155 Regulates the PI3K-AKT Pathway in Diffuse Large B-Cell Lymphoma

The aberrant expression of microRNA-155 (miR-155), which has emerged as having a significant impact on the biological characteristics of lymphocytes, plays important roles in B-cell malignancies, such as diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common non-Hodgkin's lymphoma in the adult population, accounting for approximately 40% of newly diagnosed non-Hodgkin's lymphoma cases globally. To determine the specific function of miR-155, a quantitative proteomics approach was applied to examine the inhibitory effects of miR-155 on protein synthesis in DLBCL cells. PIK3R1 (p85α), a negative regulator of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, was identified as a direct target of miR-155. A luciferase reporter was repressed through the direct interaction of miR-155 and the p85α 3'-untranslated region, and overexpression of miR-155 down-regulated both the transcription and translation of p85α. The PI3K-AKT signaling pathway was highly activated by the sustained overexpression of miR-155 in DHL16 cells, whereas knockdown of miR-155 in OCI-Ly3 cells diminished AKT activity. Taken together, our results reveal a novel target involved in miR-155 biological characteristics and provide a molecular link between the overexpression of miR-155 and the activation of PI3K-AKT in DLBCL.

Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up