Cycles Of Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone Research Articles

Induction and Maintenance Therapy in Elderly Patients with Mantle Cell Lymphoma: Double-Randomized MCL R2 Elderly Clinical Trial By the European Mantle Cell Lymphoma Network

Background: Mantle cell lymphoma (MCL) formally remains an incurable disease. Recent trials in younger patients have demonstrated the benefit of a cytarabin-containing induction (Hermine, JCO 2022) and a rituximab (Le Gouill, NEJM 2017) as well as a lenalidomide maintenance (Ladetto, Lancet Haematol 2021). The MCL-R2 elderly trial investigated whether an induction with intermediate dose of cytarabine improves long term outcome over R-CHOP alone in elderly patients (>60 yrs). In addition, responders to induction therapy were randomized between a 2 year maintenance with rituximab-lenalidomide (R2) compared to rituximab alone. Here, we present the results of the 2 randomizations. Methods: Patients >60 yrs not eligible for high dose therapy with stage II-IV MCL were included. Initially, patients were randomized between 8 cycles of 3-weekly R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or 6 cycles of alternating 3-weekly R-CHOP and 4-weekly R-HAD (rituximab, cytarabine, Dexamethasone). Subsequently, patients in complete or partial remission (CR, CRunconfirmed or PR) underwent a second randomization between rituximab maintenance every 2 months or R2 (lenalidomide 15 mg d2-22 every 4 weeks plus rituximab). Second randomization was stratified for induction regimen, study group, age, MCL international prognostic index (MIPI) and response (CR/CRu vs PR). Both maintenance regimens were continued for 24 months. The primary endpoint was EFS for the maintenance and overall survival for Induction therapy. Results: Out of 624 patients from 7 countries, 620 were randomized for induction, 492 responded (78 % ORR, CR/CRu 41%) and 495 were randomized for maintenance. Median age was 71 yrs, 69% male, 85% stage IV, 47% intermediate and 46% high risk MIPI. Response rate at the end of induction was similar in the 2 groups (OR 88% and 86% in the R-CHOP and R-CHOP/RHAD arm, respectively; CR 33% in both arms). No major safety difference were observed between the 2 induction arms. So far, PFS and OS were not different between the two induction regimen (70.6% vs. 66.8%; p=0.28 and 83% vs. 83% ; p=0.92 respectively: Figure 1A). After a median follow-up of 4.2 years from maintenance randomization, patients in the R2 maintenance arm had a significantly improved PFS in comparison to R alone. The 4-year PFS was 60.9% in the R2 arm vs. 42.9 % in the R arm (p= 0.0002, figure 1B). Adverse events (AEs) were more pronounced in the R2 maintenance arm. Recurrent (> 5%) AEs grade >3 were: neutropenia (50.8% vs 19.2%), respiratory tract infection (6.3% vs. 0.8%), and skin cancer (5.9% vs 3.2%). In 46% of patients in the R2 arm, the dose of lenalidomide had to be reduced at least once. Overall survival (OS) was not different between the two maintenance arms, (R2: 87.6% and R: 85.1% at 2 years). The majority of relapsed/refractory patients were treated with a BTK inhibitor alone or in combination (67.5%; 63% after R-CHOP and 71% after RHOP/RHAD). Conclusions: While no efficacy or toxicity differences were observed between the two induction regimens (8x R-CHOP vs 6x R-CHOP/HAD), the combined R2 maintenance significantly prolonged PFS compared to rituximab alone. However, no difference in OS was observed, and toxicity was increased in the R2 arm. Figure 1: OS(A) stratified by the CHOP and R-CHOP/RHAD arms and PFS (B) stratified by maintenance with rituximab (R) or rituximab-lenalidomide (R2) stratified by the four groups according to induction and maintenance arms.

Minimal Residual Disease (MRD) Status Predicts Outcomes in Patients with Follicular Lymphoma (FL) Treated with Chemo-Immunotherapy on SWOG S0016

Background. FL is associated with a heterogeneous clinical course, and currently available prognostic indicators are unable to reliably separate patients who exhibit early therapy resistance (POD24, defined as progression within 24 months from diagnosis) from those who achieve “functional cure” following initial therapy. NGS methods developed in recent years enabled quantification of MRD. The ClonoSeq assay (Adaptive Biotechnology, Inc.) has been FDA-cleared to track MRD in several hematologic malignancies. Here we demonstrate that MRD analysis by ClonoSeq assay predicts outcomes in a prospective cohort of patients with advanced stage FL enrolled on SWOG S0016 clinical trial. Methods. SWOG S0016 was a phase III randomized study that compared the safety and efficacy of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) with CHOP-RIT (CHOP + I 133-tositumomab) in patients with FL. Between 2001 and 2008, 531 patients with previously untreated advanced-stage FL (bulky stage II, III-IV) of any pathologic grade were randomly assigned to receive 6 cycles of R-CHOP or CHOP-RIT. We used high-throughput sequencing (HTS) of the IGH and IGK/L loci (ClonoSeq assay) from tumor biopsy specimenstaken prior to treatment to define CDR3 rearrangements that tag the tumor. Subsequently, 1-year bone marrow specimens were screened for residual disease. The baseline dominant clone was defined as ≥10 estimated number of genomes (ENG) and comprised ≥5% of the library. MRD-positive state (MRDp) was defined as a minimum Hamming distance (HD) ≤6 in a patient's post-library (in any clone also detected in a pre-library) and conserved pre-existing SHM (if HD>0). Undetectable MRD (MRDu, at <10 -4) was defined as CRD3 HD>6 in a post-library with a depth >10,000 ENG. Five-year progression-free survival was the primary endpoint (PFS; defined as the time from registration to the first observation of progression or death due to any cause). Landmark analysis was defined at 1 year after registration and used for imputing the 5-year PFS and OS. Overall survival (OS) was defined as the time from registration to date of death due to any cause or last follow-up. PFS and OS estimates and 95% confidence interval were calculated using the Kaplan-Meier method and compared for MRDp and MRDu disease using two-sided log-rank test. HR and 95% CI were calculated using Cox regression model. Results. Tumor biopsy tissue was available for 189 patients. Of these, 24 patients were not evaluable (16 did not consent for banking, 6 were ineligible and 4 had an early event). In 36 patients, pre-libraries did not yield a trackable clone. In total, MRD status could not be ascertained in 47 patients due to absence of a clear trackable clone in either pre- or post-library, contributing to a 28.8% failure rate. Of 116 patients which yielded a trackable clone in both libraries, 83 were MRDu and 33 were MRDp. Baseline characteristics (age, sex, race, β2M, B symptoms, bulky disease, grade 3, stage, and FLIPI risk) were similar between MRDp and MRDu patients; however, MRDp patients were more likely to exhibit morphologic baseline bone marrow involvement by FL (82% vs. 55%, p=0.01). The estimated 5-year PFS was 72% in MRDu patients and 30% in MRD+ patients (Figure); 10-year PFS was 56% and 17%, correspondingly. Meanwhile, 5-year OS was not different (96% for MRDu, 81% for MRD+, p=0.91). Patients with MRDu had a significantly higher best overall response rate than MRDp patients (96% vs 79%, p=0.005), but complete response (CR) rates were similar (41% vs. 30.3%). Patients who received CHOP-RIT had better PFS regardless of MRD status (HR=0.48, p=0.01 for MRDu; HR=0.38, p=0.02 for MRDp), while OS was not statistically different. Five-year PFS was superior in patients who achieved MRDu (75% for CR and 70% for PR) compared with MRDp patients, regardless of response (34%). Patients who had MRDp status had a significantly increased risk of experiencing POD24 relative to MRDu patients (RR=6.5, 95% CI 3.0-14.0; p<0.0001). Conclusion. Here we for the first time demonstrate that MRDu status, as assessed by Clonoseq, predicts improved 5- and 10-year PFS in patients with FL initially treated with chemoimmunotherapy. MRD+ status in the bone marrow at a 1-year timepoint was associated with POD24. Despite a relatively high failure rate to detect trackable sequences using current technology (~29%), MRD assessment by NGS is a promising prognostic tool in FL. *co-senior authors

Immunomodulatory AVM0703 enhances R-CHOP anti-lymphoma effect with reduced toxicity: Immune-resistant, aggressive A20 lymphoma model.

e14583 Background: Rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone (RCHOP) is the standard of care for most aggressive B-cell lymphomas. RCHOP requires numerous treatment cycles, typically 6, with challenging side effects, including toxicity and long-term secondary malignancies. Trials have demonstrated that 4 cycles of RCHOP was non-inferior to 6 with similar secondary malignancies, however, real world experience has demonstrated that long term outcomes are superior when patients achieve minimal residual disease negative (MRD-) status after the 3rd cycle (1,2). Addition of a novel agent to RCHOP that could reduce the number of cycles to 3 while maintaining response, could overcome the long-term side-effects and allow frail and elderly patients to receive full dose RCHOP in each cycle to improve outcomes. For example, addition of Lenalidomide with RCHOP improved outcomes in ABC-DLBCL patients (3), but leads to therapy related myeloid neoplasm in recent studies (4). AVM0703, an immunomodulatory drug, mobilizes bispecific and i-TCR double-positive NKT cells (AVM_NKT). In the aggressive, immune resistant A20 mouse lymphoma model, neoadjuvant AVM0703 was additive/synergistic, when cyclophosphamide/fludarabine (CyFlu) was dosed 3 + 24 hours later, with no additional toxicities. Therefore, we hypothesized that combining AVM0703 with RCHOP would be an effective and well tolerated treatment of DLBCL. Methods: Tumor-bearing mice were made by sc flank injection of 2x106 murine A20 B-cells in 10-week-old Balb/c mice. When tumor size reached established ~100 mm3, 48 mice (1:1 male: female) were randomized (12 mice each cohort) 1) Placebo 2) 1 cycle RCHOP 3) AVM0703 (18mg/kg HED) 4) AVM0703+1 cycle RCHOP combination treated as described previously (5,6). When Placebo tumors reached ~ 2000 mm3, all mice were sacrificed and tumors, blood, spleen, bone marrow were analyzed for the presence of remnant A20, and immune cell state by flow cytometer. Results: One RCHOP only mouse died from the chemo. There were no deaths in AVM0703+RCHOP group. Tumor remnant live A20 were significantly reduced in all 3 treatment groups compared to Placebo. Interestingly, AVM0703+RCHOP significantly increased the number of MRD- A20 tumors compared to RCHOP alone. Conclusions: Based on this study we plan to determine whether 3 cycles of AVM0703+RCHOP can induce long term CR and if AVM0703 could replace R and reduce long term side effects. 1) Poeschel Lancet 2019. 2) Spurgeon J Natl Canc Inst 2016. 3) Nowakowski JCO 2021. 4) Sperling Blood 2022. 5) Bascuas J Transl Med 2016. 6) Bongard PLoS Pathog 2019. [Table: see text]

Rapidly Growing Goitre: Not Always A Carcinoma.

Primary thyroid lymphoma is a rare malignancy of the thyroid gland which should be considered in rapidly growing goitres, especially when there is a history of Hashimoto's thyroiditis.A histological biopsy is preferred to minimize misdiagnoses.Surgical intervention can typically be avoided with correct diagnosis and with the use of corticosteroids to reduce compression symptoms.

Ibrutinib Plus Bendamustine Plus Rituximab and Rituximab Maintenance (I+BR) Versus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone Regimen (R-CHOP) and Rituximab, Cyclophosphamide, Doxorubicin, Bortezomib, Prednisone Regimen (VR-CAP) in First-Line Mantle Cell Lymphoma Patients: An Adjusted Treatment Comparison Using Inverse Probability Weighting

The two first/last authors contributed equally Background The phase 3 SHINE trial (NCT01776840 ) showed that I+BR significantly prolonged progression free survival (PFS) versus BR with R maintenance (BR) in older patients with previously untreated mantle cell lymphoma (1L MCL) (Wang ML et al. NEJM 2022). Other commonly used 1L MCL regimens in older patients in Europe also include rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone (R-CHOP) or a modified version of this regimen where bortezomib is substituted for vincristine (VR-CAP). In the phase 3 LYM-3002 trial (NCT00722137), VR-CAP showed improved PFS, and overall survival (OS) compared to R-CHOP (Robak T et al. Lancet 2018). In the absence of a randomized comparison of I+BR versus these treatments, we performed an adjusted comparative analysis of PFS and OS with the I+BR arm from the SHINE study and the R-CHOP and VR-CAP arms from the LYM-3002 trial. Methods In SHINE trial, patients were treated with ibrutinib once daily until disease progression or unacceptable toxicity, plus 6 cycles of BR, and patients with a partial or complete response received rituximab maintenance every 8 weeks for up to 12 additional doses. In LYM-3002 trial, patients were treated with 6-8 cycles of R-CHOP or VR-CAP and did not receive maintenance therapy. PFS was the primary endpoint for both trials. To address potential confounding bias due to lack of randomization, individual patient level data of the 2 trials were used to estimate propensity scores and apply inverse probability weighting where the R-CHOP and VR-CAP arms are reweighted to match the I+BR arm to estimate the average treatment effect of the treated (ATT) (Phillippo D et al. NICE 2019, Schneeweiss S et al. Clin Pharmacol Ther 2007). Standardized mean differences (SMD) for each baseline characteristic were calculated and considered balanced between treatment cohorts if SMD ≤ 0.25 (Li F et al. JASA 2019). Relative treatment effects are presented as hazard ratios (HR) and 95% confidence intervals (CI). Results Overall, 261 patients treated with I+BR, 134 patients with R-CHOP and 130 patients with VR-CAP were included in the analyses. Baseline characteristics (Age, Morphology, Eastern Cooperative Oncology Group (ECOG), Bone Marrow, Stage, Sex, Mantle Cell Lymphoma International Prognostic Index (MIPI)) for ATT-weighted R-CHOP and VR-CAP cohorts were well balanced versus the I+BR patient cohort. When compared to R-CHOP, the ATT adjusted PFS and OS were both statistically significantly improved with I+BR. Median PFS with I+BR vs R-CHOP is 80.8 [62.0, Not reached (NR)] vs 18.4 [13.9, 20.1] months, respectively; the PFS HR is 0.24 [0.16-0.36], p<0.001. Median OS with I+BR vs R-CHOP is NR [81.2, NR] vs 64.6 [44.6, 79.0] months, respectively; the OS HR is 0.62 [0.43-0.90], p=0.012. (Figure 1) When compared to VR-CAP, the ATT adjusted PFS was statistically significantly improved with I+BR. Median PFS with I+BR vs VR-CAP is 80.8 [62.0, NR] vs 30.7 [19.6, NR] months, respectively; the PFS HR is 0.50 [0.33-0.76], p=0.001. OS was numerically improved with I+BR. Median OS with I+BR vs VR-CAP is NR [81.2, NR] vs 64.4 [51.5, NR] months, respectively; the OS HR is 0.73 [0.51-1.05], p=0.093 (Figure 1) With one additional year of follow-up of SHINE results (median follow-up of 94.5 months), there were 110 deaths in the I+BR group and 119 deaths in the BR group, and the OS HR between I+BR vs. BR is 1.00 [95% CI 0.77-1.30]. We plan to present updated adjusted indirect comparison of OS versus VR-CAP and R-CHOP at the meeting. Conclusion In this adjusted cross-trial comparative analysis, I+BR with R maintenance demonstrated improved PFS versus two commonly used 1L MCL regimens in Europe (R-CHOP and VR-CAP). This finding is consistent with the phase 3 SHINE results where the upfront ibrutinib combination is a highly effective treatment option compared to standard chemo immunotherapies for older patients with previously untreated MCL. In addition, it also potentially supports that R maintenance should be considered routinely in patients with MCL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

ABCL-179 Primary Cranial Vault Lymphoma: Review of Cases Diagnosed at a General Hospital

Primary cranial vault lymphoma (PCVL) is a rare type of non-Hodgkin lymphoma arising outside the brain parenchyma without evidence of systemic disease. Diffuse large B cell lymphoma (DLBCL) is the most common histological subtype of PCVL. The main objective of this study was to analyze the outcome of patients with PCVL at our institution. Single-center, retrospective study. We reviewed patients with PCVL at Memorial Hermann Hospital, Texas Medical Center between 2013 and 2021. Three patients with PCVL were identified. Patients were treated with standard rituximab-based chemoimmunotherapy and radiotherapy. We analyzed the clinical presentation, objective response to treatment, rate of complete remission, and long-term clinical outcomes of patients with PCVL. Three cases (women=2, men=1) of PCVL were identified. Subject races were Hispanic (n=2) and Black (n=1). Mean age was 74 years. Two patients presented with a skull mass, and the third presented with disequilibrium, frequent falls, left-hand weakness, numbness, and forgetfulness. Positron emission tomography did not reveal any evidence of systemic disease, and bone marrow biopsy was negative in all 3 cases. Two patients underwent craniotomy and resection of the periosteal mass, whereas one patient with a scalp mass underwent diagnostic biopsy. Pathology showed DLBCL in all three cases, and fluorescent in situ hybridization showed an absence of C-MYC, Bcl-2, or Bcl-6 translocations. The Ki-67 proliferative index was noted to be high (70%-80%) in all 3 cases. One patient received 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), and another received 6 courses of dose-adjusted R-EPOCH (rituximab, etoposide, prednisone, oncovin, cyclophosphamide, and doxorubicin). Both of these patients received consolidative radiotherapy and remain in complete remission (CR) for 3 and 9 years. The third patient (80 years old) received postoperative radiotherapy at a dose of 40 Gy delivered in 20 fractions. All three achieved and remain in complete remission for 3 years, 9 years, and 7 months, respectively. PCVL is a rare lymphoproliferative neoplasm with favorable long-term outcomes. It responds well to chemoimmunotherapy and radiotherapy. Timely recognition of this rare entity can avoid unnecessary surgical intervention.

S3597 Extensive Gastric Mucormycosis in a Patient With Newly Diagnosed Diffuse Large B-Cell Lymphoma of the Stomach

Introduction: Non-Hodgkin’s lymphoma (NHL) affects the gastrointestinal tract in 10 to 15 percent of the cases. Mucormycosis in the gastrointestinal tract is rare and may cause severe infection in immunocompromised patients with hematological malignancy. We present a case of newly diagnosed diffuse large B-cell lymphoma (DLBCL) with malignant masses in the stomach and extensive ulcerations with mucormycosis. Case Description/Methods: A 62 year-old man with a history of hypertension presented with left abdominal pain and weight loss, associated with decreased appetite. Abdominal exam unremarkable, but there was a nontender left supraclavicular mass. Initial labs revealed mild microcytic anemia with elevated ferritin and C-reactive protein. Computed tomography showed multiple lymphadenopathy above and below the diaphragm with gastric wall thickening at the fundus. Upper endoscopy revealed multiple duodenal nodules, mucosal inflammation at the antrum and multiple masses with non-bleeding deep ulcers at the fundus (Figure). Biopsy revealed CD20 positive large atypical cells with flow cytometry confirming the diagnosis of DLBCL with germinal center type. Fluorescent in situ histochemistry (FISH) was negative for double-hit lymphoma. Biopsy of the ulcers also showed Mucorales identified by GMS and PAS-D stains. Patient was started on posaconazole prior to initiation of chemotherapy with R-CHOP. Discussion: The stomach is the most common gastrointestinal location of extranodal NHL. Diagnosis is confirmed by immunohistochemistry or flow cytometry. Germinal center B cell (GCB) is associated with a favorable prognosis. FISH is used to rule out double or triple-hit high-grade lymphoma with MYC and BCL2 and/or BCL6 rearrangements. Standard treatment consists of six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) with 60 percent cure rate in patients with DLBCL. Mucormycosis is caused by mold found in decaying vegetation and soil. Immunocompromised hosts are at risk of potentially fatal angioinvasive infection with local ischemia, necrosis and deep ulcerations. Gastrointestinal mucormycosis occurs in only 7% of reported cases, most commonly affecting the stomach. Empiric treatment with polyene antifungal is necessary. Surgical resection may be needed if there is massive bleeding or impending perforation. Delaying treatment increases mortality by two-fold. Early diagnosis and treatment of mucormycosis is imperative for successful outcome.Figure 1.: Endoscopic findings in the stomach; a. 5-8 mm nodular masses at the duodenal bulb; b. Scattered mucosal inflammation at the gastric antrum; c, d & e. Malignant mass with ulceration at the gastric fundus.

Rituximab-Lenalidomide(R2) Maintenance Is Superior to Rituximab Maintenance after First Line Immunochemotherapy in Mantle Cell Lymphoma: Results of the MCL R2 Elderly Clinical Trial

Rituximab-Lenalidomide(R2) Maintenance Is Superior to Rituximab Maintenance after First Line Immunochemotherapy in Mantle Cell Lymphoma: Results of the MCL R2 Elderly Clinical Trial

Updates in the Management of Early-Stage Diffuse Large B-Cell Lymphoma

Several important updates have emerged in the management of early-stage diffuse large B-cell lymphoma. Three trials resulted in the approval of rituximab + cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP) for use in these patients internationally. Furthermore, studies have been initiated to determine whether 4 or 6 cycles of this regimen should be administered without radiation therapy (RT). Six cycles of R-CHOP plus central nervous system (CNS) prophylaxis and prophylactic testicular RT are recommended for patients with extranodal disease occupying the testicles. Although controversial, there is a reasonable consensus in the literature to consider 6 cycles of R-CHOP plus involved-site RT and CNS prophylaxis for patients with extranodal disease of the breast. Patients with primary bone and gastric extranodal disease do not seem to derive a significant survival benefit from RT. Molecular subtype evaluations may change treatment approaches.

Carcinoma Camouflage

Question: A 74-year-old woman with compensated Child-Pugh A cirrhosis (Model for End-Stage Liver Disease score of 8) secondary to autoimmune hepatitis on azathioprine monotherapy was evaluated for abdominal bloating and intermittent right upper quadrant abdominal pain. She endorsed a 5-lb unintentional weight loss over the past 4 months associated with anorexia. On physical examination, she was well-appearing with a soft abdomen and no abdominal tenderness, distension, or ascites. The pertinent serology revealed an aspartate aminotransferase of 76 U/L, a total protein of 8.3 g/dL, albumin of 3.4 g/dL, hemoglobin of 12.2 g/dL, white blood cells of 3.1 × 109/L, platelets of 96,000, lactate dehydrogenase of 290 U/L, and alpha fetoprotein of 4.25 ng/mL. An abdominal ultrasound examination revealed a new hypoechoic lesion measuring 2.5 cm × 2 cm × 1.5 cm with minimal flow by Doppler. Triple phase magnetic resonance imaging (MRI) of the liver revealed a lobular 3.5 cm × 3.0 cm mass in hepatic segments 2 and 3 (Figures A and B, red arrows) as well as a 3.9 cm × 3.1 cm mass in segment 7, each T1 hypointense and T2 hyperintense with peripheral enhancement and washout including marked diffusion restriction favoring multifocal hepatocellular carcinoma with an atypical enhancement pattern. Imaging was negative for extrahepatic disease. Outside of the Milan criteria, the patient was referred to surgical oncology for further evaluation and management. The mass in segment 3 seemed to be larger via intraoperative ultrasound examination (5 cm) and was therefore resected. The mass in segment 7 underwent microwave ablation to preserve the liver parenchyma. Pathology revealed a sheetlike proliferation of large, pleomorphic, atypical vesicular lymphoid cells (Figure C) with mitotic figures and apoptotic bodies (Figure D). Immunohistologic staining was diffusely and strongly positive for CD20 (Figure E), CD10, and BCL6. Workup for viral serologies was negative (hepatitis B virus, hepatitis C virus, HIV, and Epstein–Barr virus stain from liver tissue). What is the next step in evaluation and management? What is the most likely diagnosis? Look on page 1942 for the answer and see the Gastroenterology website (www.gastrojournal.org/) for more information on submitting your favorite image to Clinical Challenges and images in GI. A referral to hematology/oncology was made for the initiation of rituximab-based chemotherapy. This patient has diffuse large B-cell lymphoma (DLBCL), germinal center B-cell type. The pathology from the resected liver segments revealed DLBCL, germinal center B-cell subtype, without double or triple-hit features after fluorescence in situ hybridization analysis. Positron emission tomography with computed tomography scans confirmed no evidence of active disease and final staging was deemed to be stage IEA with a National Comprehensive Cancer Network International Prognostic Index score of 4 (high to intermediate) secondary to age, extranodal disease, and elevated lactate dehydrogenase. Three short cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) was recommended. Echocardiogram revealed a normal ejection fraction. Unfortunately, she developed neutropenic fever during cycle 1 with extended spectrum beta lactamase urinary tract infection, urinary retention, and anasarca requiring granulocyte colony stimulating factor, antibiotics, and adjustment of diuretics. Additional chemotherapy was not advised, and she will follow-up with positron emission tomography with computed tomography scans in 2 months. DLBCL is the most common aggressive non-Hodgkin lymphoma (NHL).1Shibata J. Kurahashi S. Naito T. et al.Diffuse large B cell lymphoma primarily presenting as acute liver failure in a surviving patient.J Community Hosp Intern Med Perspect. 2019; 9: 135-139Crossref PubMed Google Scholar DLBCL may manifest as a primary hepatic lymphoma (PHL) in the late stage of disease. PHL is exceedingly rare, estimated to be present in 0.4% of extranodal NHL and 0.016% of all NHL cases.2Zhang K.J. Chen S. Chen J.L. et al.Complete response to comprehensive treatment of a primary hepatic diffuse large b cell lymphoma: a case report.Oncol Lett. 2015; 9: 1557-1660Crossref PubMed Scopus (3) Google Scholar Contributing factors include chronic viral infections (hepatitis B and C, Epstein–Barr virus, HIV), cirrhosis, autoimmune disease, and chronic use of immunosuppressants. R-CHOP is the gold standard of therapy. Chronic azathioprine use increases the risk of lymphoma; however, the association with PHL has not been reported. Imaging characteristics suggestive of PHL on MRI may consist of signal restriction in the diffusion-weighted imaging and a lower apparent diffusion coefficient.3Colagrande S. Calistri L. Grazzini G. et al.MRI features of primary hepatic lymphoma.Abdom Radiol. 2018; 43: 2277-2287Crossref PubMed Scopus (17) Google Scholar Clinicians should consider hepatic lymphoma in cirrhotic patients if there is a history of autoimmune disease, immunosuppressant use such as azathioprine, atypical enhancement pattern on MRI, and a normal alpha fetoprotein.

Risk Stratification Integrating Deauville Score on Interim PET-CT Scan and Baseline International Prognostic Index in Diffuse Large B-Cell Lymphoma Patients

BackgroundInterim 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scan may predict outcomes in patients with diffuse large B-cell lymphoma (DLBCL). However, overall accuracy in predicting treatment outcomes on adopting 5-point Deauville score (DS) was considerably low in DLBCL because of mainly low positive predictive value of interim PET-CT scans. This suggested that additional tool might be needed to more accurately predict treatment outcomes. International prognostic index (IPI) was greatly associated with outcomes for DLBCL and considered to reflect biologic aggressiveness of DLBCL. Thus, we hypothesized that combined assessments using DS on interim PET-CT scan and baseline IPI might improve the prediction of treatment outcomes in DLBCL patients. In this study, we aimed to establish the risk predicting model integrating DS on interim PET-CT as an estimate of early metabolic response and baseline IPI as a predictor of biologic aggressiveness in patients with newly diagnosed DLBCL.MethodsIn this retrospective cohort study, we consecutively enrolled patients with newly diagnosed DLBCL. Patients were eligible if they were histologically confirmed with DLBCL from Jan 2007 to June 2016, received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), and had PET-CT scan data at baseline and at interim after 3 cycles of R-CHOP. Primary CNS or transformed DLBCLs were excluded. Interim PET-CT was assessed using 5-point DS and four point or higher was regarded as positive. All PET-CT scans were assessed by 2 experienced nuclear medicine physicians, who were masked to treatment outcomes of the patients. Discrepant interpretations between 2 nuclear medicine physicians were resolved by consensus through mutual discussion.ResultsA total of 316 patients were screened for eligibility. Ninety-six patients were excluded from the analysis due to following reasons: unavailable baseline (n=9) or interim PET-CT scans (n=48), early death before interim PET-CT (n=16), Primary CNS or transformed DLBCLs (n=15), and insufficient medical records (n=8). Thus, 220 patients were analyzed. Median age was 64 years (range, 19-87) and 132 (60%) were male. Based on the IPI risk, patients were classified as the low or low-intermediate (LI; N=126, 57%), and high-intermediate (HI) or high (N=94, 43%) groups. Interim DS was determined as 1 (n=67, 30.5%), 2 (n=65, 29.5%), 3 (n=39, 17.7%), 4 (n=36, 16.4%), and 5 (n=13, 5.9%).With a median follow-up of 56.6 months (IQR 36.0-71.8), 5-year progression-free survival (PFS) rate was 65.2% (95% CI, 58.1-72.3) and overall survival (OS) rate was 69.9% (95% CI, 63.2-76.6). Interim DS (1-3 vs 4-5) and the IPI (low-LI vs HI-high) were independently associated with PFS (for interim DS of 4-5, hazard ratio [HR], 2.96 [95% CI, 1.83-4.78], P < 0.001; for HI-high IPI, HR, 4.84 [2.84-8.24], P < 0.001) and OS (for interim DS of 4-5, HR, 2.98 [1.79-4.98], P < 0.001; for HI-high IPI, HR, 5.75 [3.14-10.51], P < 0.001) in the multivariate analysis. We stratified patients into 3 groups based on the risk of progression: Low (low-LI IPI and interim DS 1-3), Intermediate (low-LI IPI with interim DS 4-5, or HI-high IPI with interim DS 1-3), and High (HI-high IPI and interim DS 4-5) risk groups. The risk stratification model showed a significant association with PFS (for low risk vs intermediate risk, HR 3.98 [95% CI, 2.10-7.54], P<0.001; for low risk vs high risk, HR 13.97 [7.02-27.83], P<0.001; Fig 1A) and OS (for low risk vs intermediate risk, HR 4.14 [2.01-8.54], P<0.001; for low risk vs high risk, HR 16.05 [7.59-33.94], P<0.001; Fig 1B).ConclusionCombining interim DS with baseline IPI can improve risk stratification in patients with newly diagnosed DLBCL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Rituximab Maintenance Therapy Is an Effective Therapy in over-Sixties with Mantle Cell Lymphoma

IntroductionMantle cell lymphoma (MCL) is a rare B-cell non-Hodgkin lymphoma (NHL) accounting for 5 percent of NHLs. Most patients with MCL are 60 years of age and older. The prognosis of patients with MCL is moderately aggressive and variable; the median overall survival is 3-5years. MCL international prognostic index(MIPI)is related to prognosis of the patients with MCL, however, it is unclear whether MIPI predicts outcomes of MCL over sixties. Out therapeutic strategy in elderly patients with newly diagnostic MCL is not high-dose chemotherapy with autologous stem cell transplantation. Instead of aggressive chemotherapy, Rituximab maintenance is considered as an effective and feasible option.Thus, we investigated whether MCL international prognostic index (MIPI) relates overall survival (OS) or progression free survival (PFS), and whether maintenance therapy with Rituximab improved OS or PFS in patients with newly diagnosed MCL patients 60 and older.MethodsWe analyzed retrospectively 60 years of age and older patients with MCL who have achieved complete response (CR) or partial response (PR) after induction chemotherapy with rituximab at our hospital from December 2005 to February 2015. Two of primary refractory patients were excluded because analysis is for patients who are eligible for rituximab maintenance therapy. The patients were diagnosed by hematopathologist in our hospital. According to the MIPI, patients were stratified into low risk (0 patients, 0%), intermediate risk (9 patients, 41%), and high risk (13 patients, 59 %). Induction chemotherapy regimens were six cycles of R-CHOP (rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone), four cycle of R-hyper CVAD/MA (rituximab-cyclophosphamide-vincristine-doxorubicin-dexamethasone alternating with rituximab-methotrexate-cytarabine), six cycles of R-CVP (rituximab- cyclophosphamide-vincristine-predonisone), R-VP16 (rituximab-etoposide), or six cycles of VR-CAP (bortezomib-rituximab-cyclophosphamide-doxorubicin- predonisone). Rituximab maintenance therapy started 6 months after the last induction chemotherapy and underwent four weekly infusion every 6 months for 2 years.ResultsA total of 22 MCL patients were analyzed. The number of patients who had achieved CR was 14 and PR was 8. 14 of 22 patients were treated rituximab maintenance. Median age was 73 years old. MIPI could predict OS of MCL. 3-year-OS was significantly superior intermediate risk to MIPI high risk (3-years-OS: 87.5 %vs.51.9 %,p=0.0232), whereas PFS didn't have correlation with MIPI(3-years PFS70.0 %vs.38.5 %,p=0.136). 3-years OS was significantly superior maintenance group to no maintenance group (3-years survival rate 91.7 % vs. 25.0 %, p=0.00188, figure 1), and 3-years PFS tend to improve in the maintenance group (3-years PFS, 65.8 % vs.25.0 %, p=0.0773, figure 2).Conclusion:In this study, MIPI correlates with OS, however doesn't show with PFS. Rituximab maintenance therapy is effective, and prolongs OS for 60 years of age and older patients with MCL. [Display omitted] [Display omitted] DisclosuresNishimura:Chugai Pharmaceutical CO., LTD.: Consultancy. Mishima:Chugai Pharmaceutical CO., LTD.: Consultancy. Yokoyama:Chugai Pharmaceutical CO., LTD.: Consultancy. Hatake:Chugai Pharmaceutical CO., LTD.: Other: lecture speaking.

Treatment of high-risk aggressive B-cell non-Hodgkin lymphomas with rituximab, intensive induction and high-dose consolidation: long-term analysis of the R-MegaCHOP-ESHAP-BEAM Trial

We have studied the feasibility and efficacy of intensified R-MegaCHOP-ESHAP-BEAM therapy in high-risk aggressive B-cell lymphomas. Altogether 105 patients (19–64 years) with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBL) or follicular lymphoma grade 3 (FL3) with an age-adjusted International Prognostic Index of 2–3 were recruited. Treatment consisted of three cycles of high-dose R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), followed by three cycles of R-ESHAP (rituximab, etoposide, methylprednisolone, cytarabine, cisplatin) and high-dose consolidation with BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous stem cell transplant. The 5-year progression-free survival (PFS) was 72% (DLBCL 60%, PMBL 89%) and overall survival (OS) was 74% (DLBCL 61%, PMBL 89%) after a median follow-up of 85 months. However, an independent prognostic factor was age only, with patients ≤ 45 years having 5-year PFS 90% and patients > 45 years having PFS 54%. PMBL had better prognosis than DLBCL/FL3 in patients > 45 years (PFS, 88% vs. 48%), but not in younger patients (PFS, 91% vs. 94%).

R‐CHOP therapy alone in limited stage diffuse large B‐cell lymphoma

Long-term observation has identified a pattern of continuing relapse in limited stage diffuse large B-cell lymphoma (DLBCL) treated by three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) plus involved-field irradiation. We retrospectively analysed 190 untreated patients with limited stage DLBCL treated by R-CHOP alone. All the patients were scheduled to undergo primary therapy with six cycles of full-dose R-CHOP. Cases with a dose reduction of more than 20% were excluded from the study. Additional local irradiation was allowed in patients with partial response (PR). Five patients received additional local irradiation after PR at the end of the R-CHOP therapy. The median observation period was 52 months. Median age at diagnosis was 63 years. The responses to therapy were 180 complete responses, eight PR, and two progression of disease (PD). The 5-year progression-free survival and 5-year overall survival rates were 84% and 90%, respectively, both in plateau. During the observation period, 29 patients experienced PD. The progression sites were the primary sites in 15 patients, outside the primary sites in 10, and undetermined in four patients. These results suggest that the 'standard' strategy of three cycles of R-CHOP followed by involved-field radiotherapy for limited stage DLBCL could be effectively replaced by six cycles of R-CHOP alone.

Significant Prognostic Impact of [18F]Fluorodeoxyglucose-PET Scan Performed During and At the End of Treatment with R-CHOP in High-Tumor Mass Follicular Lymphoma Patients: A GELA-GOELAMS Study

Abstract 877 Introduction:Patients with follicular lymphoma (FL) usually respond well to immuno-chemotherapy as initial treatment and can have long survival times. However, a small proportion of patients are refractory or have early relapses. Early identification of this subgroup of patients could lead to early therapeutic changes and, potentially, to a better prognosis. [18F]Fluorodeoxyglucose-Positron Emission Tomography (FDG-TEP) is widely used for the staging and restaging of aggressive lymphoma patients but little is known about the use of FDG-PET in patients with FL, except that FL is almost uniformly FDG-avid. FDG-PET is not recommended today as a routine procedure in FL patients (Cheson et al. J Clin Oncol 2007). In this first prospective, multicentric study, we evaluated the prognostic value of FDG-PET performed at mid-treatment and at the end of treatment in patients with high-tumor mass FL treated with immuno-chemotherapy in first line. Patients & methods:Patients with previously untreated FL (grades 1–3A) presenting with a high tumor burden as defined by the GELF criteria, were treated with 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) plus 2 cycles of rituximab, given every 21 days. Patients did not receive rituximab maintenance. A FDG-PET was performed before treatment, after 4 cycles of R-CHOP (interim FDG-PET: I-PET), and at the end of treatment (final PET: F-PET). FDG-PET scans were first interpreted in each centre, then centrally reviewed by 3 investigators blinded to clinical data. Positivity or negativity was rated according to the Deauville visual semi-quantitative criteria (Meignan M: Leuk Lymphoma 2009), positivity being defined as a fixation at level 4 (FDG uptake superior to that of the liver) or 5 (uptake clearly superior to liver and/or new sites of disease). Results:121 patients were included. The median age was 57 years and the male-to-female ratio was 1.12. Ninety-three percent had Ann Arbor stage III–IV. Ninety-seven percent had a good performance status (ECOG score 0–1). The repartition according to the FLIPI was: 0–1 factors: 15%; 2 factors: 43%; 3–5 factors: 42%. The Kappa coefficient indicated a good degree of concordance between the 3 PET reviewers. The initial FDG-TEP was positive in all except 1 case out of 118 centrally reviewed cases. After central review, I-PET (n=111) was negative in 76% of patients and F-PET (n=106) was negative in 78%. With a median follow-up of 23 months, 2-year-progression-free survival rates for I-PET negative versus positive and for F-PET negative versus positive were I-PET 86% versus 61% (p=0.0046); F-PET 87% versus 51% (p <0.0001), respectively. Two year OS at the end of treatment also significantly differed according to F-PET results: 100% vs 88% (p = 0.0128). Conclusion:In FL patients treated in first line, FDG-PET performed either after 4 cycles of R-CHOP or at the end of immunochemotherapy induction is strongly predictive of outcome. Therapeutic intervention based on TEP results during inductive treatment should be evaluated in the future. Disclosures:Salles:Roche and/or Genetech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genzyme: Membership on an entity's Board of Directors or advisory committees; Calistoga/Gilead: Membership on an entity's Board of Directors or advisory committees.

Composite T lymphoblastic leukemia/lymphoma and diffuse large B-cell lymphoma: Case report

This report concerns a unique case of a composite lymphoma composed of T-lymphoblastic leukemia/lymphoma (T-LBL) and diffuse large B-cell lymphoma (DLBCL) in a 72-year-old woman with generalized lymphadenopathy, splenomegaly and ascites. Laboratory findings showed increased lactate dehydrogenase and soluble interleukin-2 receptor. The biopsy specimen showed replacement of the normal architecture of the lymph nodes by a tumor containing a dual cell population composed of large lymphocytes and medium-sized lymphocytes. Sheets of large lymphocytes often were punctuated by clusters of medium-sized lymphocytes. Flow cytometry and immunohistochemical analysis showed a composite lymphoma with both T-LBL and DLBCL. The T-LBL expressed CD1a, CD3, CD4, CD8, and terminal deoxynucleotidyl transferase. The DLBCL expressed CD19 and CD20, CD23, bcl-2, bcl-6, MUM1 and immunoglobulin κ light chain. Polymerase chain reaction detected a monoclonal pattern of T-cell receptor γ and immunoglobulin heavy chain rearrangements in the same specimen. She received eight cycles of R-CHOP (rituximab+cyclophosphamide, doxorubicin, vincristine, prednisone) therapy and achieved complete remission. She has shown no signs of recurrence 20 months after the diagnosis. We describe here a very unusual and, to the best of our knowledge, an as yet never reported case of a primary composite lymphoma of T-LBL and DLBCL.

Phase II Study of R-CHOP Followed by 90Y-Ibritumomab Tiuxetan in Untreated Mantle Cell Lymphoma: Eastern Cooperative Oncology Group Study E1499.

Background: As MCL has a continuous relapse pattern with current treatments, we designed a study to determine the safety and efficacy of the anti-CD20 radio-immunoconjugate,90Y-ibritumomab tiuxetan (90Y-RIT), following 4 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) induction.Methods: Patients (pt) with untreated stage II-IV MCL (CD20+, cyclin D1+) ≥18 yr with measurable/evaluable disease and adequate organ function were eligible. At 4–8 weeks after 4 cycles of R-CHOP, responding (CR/PR) and stable pt received 0.4 mCi/kg 90Y-RIT. The primary endpoint was failure-free survival (FFS) and secondary objectives were evaluation of response and toxicity after R-CHOP and after 90Y-RIT. The study design required 52 eligible pt to demonstrate a prolongation of FFS by 50% compared with R-CHOP alone (median FFS 16 mo, Howard et al., JCO 20:1288, 2002).Results: The characteristics of 56 eligible pt are: 73% male, median age 61 (33–83) yrs, 91% stage III/IV, 68% >1 extranodal site, 78% marrow-positive. IPI was 0–2 in 51%, 3–5 in 49%. Fifty-one (91%) pt received all treatment and best response (n=50) was 42% CR/CRu, 32% PR, 12% stable and 4% unevaluable, with an improvement in response in 16 pt after 90Y-RIT. After 90Y-RIT, 55% had grade 3/4 neutropenia with no febrile neutropenia and 45% had grade 3/4 thrombocytopenia with recovery at 12 weeks in 22/23 pt. Median follow-up (all pt) is 24.4 months. Median FFS for all 56 pt is 27 months with an estimated 71% FFS and 93% overall survival at 18 months. Among pt who completed all treatment and have been followed ≥1.5 yr (n=45), 33 remain failure-free and 12 have progressed (4 dead).Conclusions: 90Y RIT after 4 cycles of R-CHOP in untreated MCL is safe and improves the number and quality of responses. These data suggest prolongation of FFS over that expected with R-CHOP alone. Consolidation of remission in MCL with 90Y-RIT shows potential as a strategy to prolong remission duration and is applicable to most pt with MCL. However, longer follow-up in needed to evaluate the durability of remissions achieved.

B-Cell Lymphoma During Pregnancy Associated with Hemophagocytic Syndrome and Placental Involvement

We report a case of B-cell lymphoma during pregnancy associated with hemophagocytic syndrome and placental involvement. A 33-year-old Japanese woman developed pancytopenia, hepatosplenomegaly, and a high-grade fever for 2 weeks at 23 weeks of gestation. The demonstration of hemophagocytes in her bone marrow confirmed the diagnosis of hemophagocytic syndrome. She was referred at 25 weeks of gestation for evaluation of hemophagocytic syndrome. The screening for infection and autoimmune disease was negative. Clinical manifestation suggested malignant lymphoma as the underlying cause of hemophagocytic syndrome, but we could not confirm any lymphoma involvement in the bone marrow aspiration. Glucocorticoid therapy did not arrest the hemophagocytic process. Her general status worsened, and reduction of amniotic fluid was noted. At 28 weeks of gestation, we performed a Cesarean section because of fetal distress. Microscopic examination of placental specimen revealed diffuse infiltration of large, atypical lymphoid cells involving the intervillous space. Using immunohistochemical study, we made the diagnosis of B-cell lymphoma. R-CHOP (rituximab/ cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy was administered on the eighth postpartum day. After 2 cycles of R-CHOP chemotherapy, hematopoiesis became normal and hepatosplenomegaly almost completely disappeared. After 6 cycles of R-CHOP, the patient received autologous peripheral-blood stem cell transplantation, and she is currently in complete remission 1 year after diagnosis. The infant did well, without clinical or laboratory manifestations of malignant lymphoma. In cases with suspected malignancy associated with hemophagocytic syndrome during pregnancy, it is important to verify placental microscopic examination for evaluating the causative disease of hemophagocytic syndrome.

Community-Based Trial of R-CHOP and Maintenance Rituximab for Intermediate- or High-Grade Non-Hodgkin Lymphoma with First-Cycle Filgrastim for Older Patients

Background:Administration of full-dose R-CHOP (rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy is important to maximize response in patients with intermediate-or high-grade non-Hodgkin lymphoma but might be difficult in older patients. Patients and Methods:This community-based study was conducted to determine response, toxicity, and disease-free survival in patients with intermediate-or high-grade non-Hodgkin lymphoma receiving R-CHOP with filgrastim. Patients received 6-8 cycles of R-CHOP followed by 4 cycles of maintenance rituximab for responders. Patients aged > 60 years or with increased infection risk received filgrastim 5 μg/kg per day in all R-CHOP cycles; other patients received filgrastim after a neutropenic event (no planned administration for cycle 1). Results:Of 101 patients enrolled, 60 (59%) were aged > 60 years and received filgrastim in all cycles. Thirty-three patients aged ≤ 60 years (80%) received filgrastim, 7 (17%) as primary use in cycle 1. Chemotherapy average relative dose intensity was comparable between age groups (91% > 60 years vs. 93% ≤ 60 years). Overall response was similar in both groups (87% > 60 years vs. 95% ≤ 60 years; P = 0.19); however, the complete response rate was significantly lower for older patients (42% > 60 years vs. 71% ≤ 60 years; P = 0.005). Seventy-six percent of patients (75% > 60 years vs. 78% ≤ 60 years) had no evidence of progression after 2 years of follow-up. Febrile neutropenia (fever ≥ 38.3°C with absolute neutrophil count < 500/mm) occurred in 17% of patients overall (22% > 60 years vs. 10% ≤ 60 years), and 8% had cycle-1 events (12% > 60 years vs. 2% ≤ 60 years). Conclusion:Patients aged > 60 years receiving R-CHOP with filgrastim support in all cycles received comparable doses of chemotherapy and had similar overall response rates compared wtih those of younger patients receiving no preemptive cycle-1 filgrastim.

Phase II study of rituximab + CHOP followed by 90Y-ibritumomab tiuxetan in patients with previously untreated mantle cell lymphoma: An Eastern Cooperative Oncology Group Study (E1499)

7503 Background: Because mantle cell lymphoma (MCL) has a continuous relapse pattern with current treatments, we designed a study to determine the safety and efficacy of the anti-CD20 radio-immunoconjugate,90Y-ibritumomab tiuxetan (90Y-RIT), after R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) induction. Methods: Patients (pt) with untreated stage II-IV MCL (CD20+, cyclin D1+) ≥18 yr were eligible if they had measurable/evaluable disease, adequate organ function (WBC &gt;2,500/μl; platelets &gt;100,000/μl unless marrow-positive) and gave informed consent. At 4–8 weeks after 4 cycles of R-CHOP, stable and responding pt meeting standard marrow and hematologic criteria received 0.4 mCi/kg 90Y-ibritumomab tiuxetan. Objectives were to evaluate response and toxicity after R-CHOP and 90Y-RIT with a primary endpoint of time to treatment failure (TTF). Results: 56 of 57 accrued patients are eligible pending central pathology review. Characteristics included 73% male, median age 60 (33–83) yrs, 91% stage III/IV, 64% &gt;1 extranodal site, 75% marrow-positive. IPI was 0–2 in 50%, 3–5 in 43% and unknown in 7%. After 90Y-RIT 53% had grade 3/4 neutropenia with no febrile neutropenia and 45% had grade 3/4 thrombocytopenia with recovery at 12 weeks in 19/20 pt. 50 pt are evaluable for response after R-CHOP and 44 pt after 90Y-RIT. Best response after R-CHOP (n = 50) was: CR/CRu 14% (n = 7), PR 58% (n = 29), SD 26% (n = 13), PD 2% (n = 1). After 90Y-RIT, responses improved in 15 of 37 pt with &lt;CR/CRu: PR to CR/CRu (n = 12) and SD to CR (n = 1) or PR (n = 2) for a final response rate of 84% and CR rate of 45%. Conclusions: 90Y RIT after 4 cycles of R-CHOP in untreated MCL is safe and improves the number and quality of responses. Further follow-up is needed to determine TTF. [Table: see text]