bluuebunny/crossref_metadata_2025_split huggingface dataset:
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)
Authors: Smith M. R. , Chen H. , Gordon L. , Foran J. , Kahl B. , Advani R. , Gascoyne R. D. , Weller E. , Horning S. J. 
Published: March 2020

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 >2,500/μl; platelets >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% >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 <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]
Recommendations for revised response criteria for malignant lymphoma
Authors: Cheson B. D. , Pfistner B. , Juweid M. E. , Horning S. J. , Coiffier B. , Gascoyne R. D. , Fisher R. I. , Hagenbeek A. , Hoppe R. T. , Diehl V. 
Published: March 2020

7507 Background: Standardized response criteria are needed to interpret and compare clinical trials, and for approval of new therapeutic agents by regulatory agencies. Methods: The International Working Group (IWG) criteria (Cheson et al, JCO 17:1244, 1999) were widely adopted but were reevaluated because of limitations identified, and recent advances, notably FDG-PET, immunohistochemistry (IHC) and flow cytometry. Results: We propose the following modifications for non-Hodgkin’s lymphoma (NHL) and Hodgkin lymphoma (HL). For predictably PET avid histologies (PA)(e.g., diffuse large B-cell NHL (DLBCL), HL, follicular (FL) and mantle cell lymphoma (MCL), PET pretreatment is strongly encouraged to define sites of disease, but not required. For histologies not predictably PET+ (NPA), PET should only be done if response is an endpoint. Although PET performed after ≥1 cycles of chemotherapy correlates with treatment efficacy, in the absence of data that altering therapy because of PET results improves outcome, mid-treatment PET should only be done in a clinical trial. PET is essential to assess response in DLBCL and HL, but only in FL and MCL if response is the endpoint. For NPA histologic subtypes, PET should only be used if PET+ prior to therapy and response is a major endpoint. Present data are inadequate to recommend PET for routine post-treatment surveillance. The new definition for CR includes: 1) no signs or symptoms of disease; 2) PET- in a PA lymphoma, or negative CT in NPA lymphoma. 3) Normal bone marrow by morphology, or if indeterminate, negative by IHC, flow and/or molecular genetic studies. CR unconfirmed (CRu) is no longer included. PR is defined as 1) ≥ 50% decrease in tumor size, but PET+ at prior PA sites, or 2) ≥ 50% decrease in tumor size, but CT+ and PET- if PET- prior to treatment. Bone marrow is irrelevant if positive pre-treatment. Stable disease is neither PR nor progressive disease, PET+ only at prior sites of disease. Progressive/ relapsed disease requires ≥ 50% increase in disease or new lesions that are PET+ if PA lymphoma. PET does not replace a biopsy before initiating new therapy. Conclusions: We hope these revised recommendations will be adopted by study groups and regulatory agencies to facilitate the development of new and more effective therapies to improve patient outcome. No significant financial relationships to disclose.
Update of the FL2000 randomized trial combining rituximab to CHVP-Interferon in follicular lymphoma (FL) patients (pts)
Authors: Foussard C. , Mounier N. , Van Hoof A. , Delwail V. , Casasnovas O. , Deconinck E. , Tilly H. , Fitoussi O. , Gressin R. , Salles G. , Gela-Goelams  
Published: March 2020

7508 Background: The GELA-GOELAMS FL2000 trial investigated the role of rituximab in the first line treatment of FL pts. Methods: This prospective randomized study compared the CHVP regimen (12 courses) +18 months α2b-IFN (CHVP-I) to 6 CHVP courses combined with 6 rituximab infusions + 18 months IFN (R-CHVP-I). The primary endpoint was event-free survival (EFS). Inclusion criteria consisted in untreated stage II-IV FL pts; 18–75 years old; with a high tumor burden defined by at least one of the following criteria: B symptoms, ECOG PS>1, LDH>normal value, β2-microglobulin ≥3 mg/L, largest tumor ≥7 cm, 3 distinct nodes ≥3 cm, serous effusion, compression or symptomatic spleen enlargement. Results: From 05/00 until 05/02, 358 eligible pts were randomized (CHVP-I 183 pts and R-CHVP-I 175 pts) with the following characteristics: M/F = 1; median age = 60 years [25–75]; ECOG > 1 = 8%; B symptoms = 27%; AA stage > II = 87%; bone marrow involvement = 58%; β2-m ≥3 mg/L = 31%; LDH > N = 37%; Hb <12 g/dL = 18%; FLIPI score ≥3 in 57% of the pts. The first analysis [ASH 2004] showed a significant better treatment response in R-CHVP-I as compared to CHVP-I and a improvement of event free survival (EFS) in the R-CHVP-I arm (Log-Rang, P = .003). As initially planned, a second analysis on all pts has now been performed with a median follow-up of 3½ years, all pts with data >01/01/05. The median EFS for the whole population has not yet been reached. In the CHVP-I arm, median EFS was 3 years and 46% of the pts are event-free at 42 months (mo.). In contrast, the median has not been reached in the R-CHVP-I arm and the EFS is 67% at 42 mo. (P < .0001). This improvement in EFS was found both in the 150 pts with a low or intermediate FLIPI score (P = .019) and in those (n = 201) with a high score (P = .0005). When considering the 230 pts responders at the end of 18 mo. of therapy, 42 mo. EFS is 62% in CHVP-I arm versus 81% in R-CHVP-I arm (P = .002). Finally, the overall survival at 42 mo. of patients in the CHVP-I arm is of 84% versus to 91% in the R-CHVP-I arm (P = .029) with a reduction of death risk by approximately 2 (RR = 0.55). Conclusions: These results demonstrate that rituximab combined with CHVP-I has a durable benefit, in all FLIPI risk groups, allows to reduce the duration of chemotherapy and improves overall survival in high-tumor burden FL pts. [Table: see text]
Bortezomib in relapsed or refractory mantle cell lymphoma (MCL): Results of the PINNACLE study
Authors: Goy A. , Bernstein S. H. , Kahl B. S. , Djulbegovic B. , Robertson M. J. , Boral A. , Shi H. , Fisher R. I. 
Published: March 2020

7512 Background: Bortezomib (VELCADE, Vc), a novel proteasome inhibitor, is approved in relapsed multiple myeloma and has shown activity in MCL in phase 2 NHL studies. Methods: Patients (pts) with relapsed or refractory MCL with a maximum of 2 prior therapies received Vc 1.3mg/m2 i.v. on d 1, 4, 8, and 11 of a 21-d cycle for up to 1y. Full accrual (155 pts) was completed in this multicenter, phase 2 study. Primary endpoint was TTP, secondary endpoints included RR and duration of response (DOR). Response (International Workshop Criteria) was assessed by the investigators and separately by the sponsor using central radiology review. Results: Data are available for 154 pts. Baseline characteristics included median age 65y, 81% male, 28% KPS <90%, 35% LDH > normal, 43% IPI ≥3, 74% stage IV MCL. 90% of pts had prior intensive therapy (e.g. Hyper CVAD, CHOP, EPOCH), 96% had prior rituximab, and 14% had prior stem cell transplant. Median duration of Vc treatment was 4 cycles. 138 pts were evaluable for response. By investigator assessment, RR was 35% (CR + CRu = 8%) and median DOR was 9.2 mo. Median TTP was 5.5 mo (all patients, n = 154). Using central radiology review RR was 31% (CR + CRu = 7%), median DOR was 4.6 mo and median TTP was 4.1 mo. With median follow-up of 10 mo, median survival has not been reached. The most common non-hematologic AEs were fatigue (14% ≥grade 3), GI events (≥grade 3 diarrhea, abdominal pain, and nausea/vomiting in 5%, 4%, and 3%, respectively), and peripheral neuropathies (7% ≥grade 3). Hematologic toxicities were minimal except for transient thrombocytopenia (10% ≥grade 3), as previously seen with Vc. Conclusions: This study confirms the activity of Vc in relapsed/refractory MCL in a multicenter international setting and supports its rapid development as a new treatment for relapsed MCL. Vc is also being studied in the first-line setting in combination with standard chemotherapy. [Table: see text]
Lack of necessity of granuloctye-colony stimulating factor (GF) in Hodgkin’s disease (HD) treated with ABVD
Authors: Evens A. M. , Cilley J. , Gounder M. , Ortiz T. , Miyata S. , Catsaros K. , Rademaker A. , Tallman M. S. , Winter J. N. , Gordon L. I. 
Published: March 2020

7515 Background: DI is important in the therapy of HD, and GF has been used to maintain DI. Recent data suggest that toxicity (bleomycin pulmonary toxicity [BPT]) is higher in patients (pts) who receive GF (JCO 2005;23:7614). We reviewed all HD pts treated since Jan 1996 with attention to GF use, DI, blood counts, BPT and survival. Methods: We analyzed biopsy-confirmed HD pts who received all of their therapy at NU from Jan 1996 to Oct 2005. BPT was defined as: pulmonary symptoms, bilateral infiltrates on scans and no infection. Results: We identified 95 pts, of whom 77 (81%) received ABVD, 7 (7.4%) Stanford V, and 11 (11.6%) other. Of the 77 ABVD pts, 51 completed all cycles with no GF, 23 received GF and 3 are unknown. In the “no GF” group, median age was 31 yrs, 31% had stage III/IV disease (33% Hasenclever Index > 3); 18% had bulky disease, 37% B symptoms and 53% received radiation (RT). In the GF group (n = 23), median age was 33, 42% had stage III/IV disease (21% Hasenclever index > 3); 17% had bulky disease, 42% B symptoms and 50% had RT. Among the 51 “no GF” ABVD pts (287 cycles), median treatment-day ANC were 0.9, while % monocytes were consistently elevated (see Table). There were no dose adjustments or treatment delays for ANC on day of treatment. Normalized DI was > 99% for all treatment days and median cycle duration was 28.6 days (planned = 28 days). 1/51 of these pts had BPT and 2 episodes of uncomplicated neutropenic fever were seen (2/287 cycles = 0.6% incidence). If Stanford V pts are included (n = 7, 2 without and 5 with GF), BPT occurred in 1/53 with “no GF” and 2/28 with GF (see Table). CR rate (100%), PFS and OS were similar in all groups (see Table). Conclusion: 1) GF is not necessary in order to administer ABVD at > 99% DI, and its absence is associated with low toxicity. 2) ABVD should be given at 100% dose with no delay despite ANC on day of treatment. 3) GF should not be used routinely in HD pts treated with ABVD. [Table: see text] No significant financial relationships to disclose.
Lenalidomide plus high-dose dexamethasone provides improved overall survival compared to high-dose dexamethasone alone for relapsed or refractory multiple myeloma (MM): Results of a North American phase III study (MM-009)
Authors: Weber D. M. , Chen C. , Niesvizky R. , Wang M. , Belch A. , Stadtmauer E. , Yu Z. , Olesnyckyj M. , Zeldis J. , Knight R. 
Published: March 2020

7521 Background: Lenalidomide is a novel, orally administered, immunomodulatory drug (IMiD) that has single-agent activity against MM and additive effects when combined with dexamethasone (Dex). Methods: In this phase 3, multicenter, double-blind trial, 354 patients (pts)with relapsed or refractory MM were treated with Dex 40 mg daily on days 1–4, 9–12, 17–20 every 28 days and were randomized to receive either lenalidomide (Len) 25 mg daily orally on days 1–21 every 28 days or placebo. Beginning with cycle 5, Dex was reduced to 40 mg daily on days 1–4 only, every 28 days. Patients were stratified with respect to B2M (≤ 2.5 vs. > 2.5 mg/mL), prior stem cell transplant (none vs. ≥ 1), and number of prior regimens (1 vs > 1). The treatment arms were well balanced for prognostic features. Results: The overall response rate was greater with Len-Dex than with Dex-placebo (59.4% vs. 21.1%; p < 0.001). Complete responses were achieved in 12.9% of pts treated with Len-Dex and 0.6% of pts treated with Dex-placebo. The median time to progression (TTP) for pts treated with Len-Dex was 11.1 months compared to 4.7 months for pts treated with Dex-placebo (p < 0.000001). Median overall survival was higher with Len-Dex (not reached) compared to Dex-placebo (24 months) (hazard ratio 1.76, p = .0125). Grade 3–4 neutropenia was more frequent with combination therapy than with Dex-placebo (24% vs. 3.5%), however ≥ grade 3 infections were similar in both groups. Thromboembolic events occurred in 15% of pts treated with Len-Dex and in 3.5% of pts treated with Dex-placebo. Atrial fibrillation occurred in 8 pts and CHF developed in 4 pts treated with Len-Dex. Conclusions: Considering the ease of oral administration, higher response rate, longer time to progression and overall survival benefit, the combination of lenalidomide-dexamethasone may very well represent the treatment of choice for early refractory or relapsing multiple myeloma. The relatively infrequent side effects should not detract from these improvements, but the use of prophylactic antithrombotic therapy should be considered for patients treated with the combination of lenalidomide and dexamethasone. [Table: see text]
Phase II study of alemtuzumab in lymphoplasmacytic lymphoma: Results of WMCTG trial 02–079
Authors: Hunter Z. R. , Boxer M. , Kahl B. , Patterson C. J. , Soumerai J. D. , Treon S. P. 
Published: March 2020

7523 Background: Alemtuzumab (Campath-1H) is a fully humanized anti-CD52 antibody used to treat B and T-cell disorders. CD52 is widely expressed on bone marrow lymphoplasmacytic cells and growth supporting mast cells in patients with lymphoplasmacytic lymphoma (LPL), including Waldenstrom’s macroglobulinemia (WM). We therefore examined the activity of alemtuzumab in LPL. Methods: 28 patients with LPL, including 27 WM patients were enrolled in this multicenter study. 23 patients were previously treated. Median age was 60 (range 33–75 years), median prior therapies was 2 (range 0–5), and median time from diagnosis was 2.9 (range 0.1–9.0 years). Baseline median bone marrow involvement was 30% (range 5–90%), median serum IgM was 3510 (range 622–12,000 mg/dL) and hematocrit was 35.1 (range 24.4–42.8%). Patients received 3 test doses of alemtuzumab (3, 10, and 30mg IV) followed by 30 mg TIW for up to 12 weeks. All patients received acyclovir and bactrim or equivalent prophylaxis. Results: Twenty-five patients are evaluable for response. 24/25 patients demonstrated a decrease in serum IgM levels (median change -40.5%), for an overall response rate of 76%, which included 8 (32%) partial responders (≤50% decrease in serum IgM), and 11 (44%) minor responders (≥25% decrease in serum IgM). Hematological toxicities were common among previously treated (but not untreated) patients and included G3/4 neutropenia 39%; thrombocytopenia 18%; anemia 7%. G3/4 non-hematological toxicity for all patients included dermatitis 11%; fatigue 7%; and infection 7%. CMV reactivation and infection was commonly seen among previously treated patients and may have been etiological for one death on study. Two other patients also succumbed on study, one related in part to drug therapy for CMV infection and another due to complications of therapy induced thrombocytopenia and Von Willebrand disease. With a median follow-up of 8.5+ months, 11/19 responding patients remain free of progression. Conclusions: Alemtuzumab is highly active in patients with LPL. Hematological and non-hematological toxicities, including CMV reactivation and infection are common among previously treated patients. Further exploration of this agent in LPL, including upfront therapy is warranted. No significant financial relationships to disclose.
Very long term outcome of patients with gastric marginal zone B cell lymphoma of mucosa associated tissue (MALT) following Helicobacter pylori (Hp) eradication therapy
Authors: Chini C. , Proserpio I. , Giudici M. E. , Pinotti G. , Pozzi B. , Capella C. 
Published: March 2020

7531 Background: Hp infection plays a decisive role in the pathogenesis of low-grade gastric MALT lymphoma and eradication therapy has become a widely accepted initial treatment of stage I disease. The aim of this study was to evaluate the long term outcome of patients (pts) with localized gastric MALT lymphoma exclusively treated with Hp eradication therapy. Methods: a prospective series of 62 newly diagnosed IE gastric MALT lymphoma pts (29M/33F) with median age of 63 years (range 27–87), referred to our department from June 1991 to January 2004 were evaluable for the study. Diagnosis was histologically proved and Hp status was evaluated. Staging was performed according to the modified Ann Arbor system. All pts received the triple eradicating therapy (OMC: omeprazole 20 mg bid, metronidazole 400 mg bid and clarithromycin 500 mg bid or OAC: omeprazole 20 mg bid, amoxycillin 1,000 mg bid and clarithromycin 500 mg bid) for one week. Response, evaluated every 6 months with multiple biopsies, was graded according to the Wotherspoon’s histologic scoring system. Results: Hp was eradicated in all patients, but 8 pts required a second line antibiotic therapy; symptoms disappeared or markedly diminished and endoscopic features improved in all pts. Histological remission (score 0–2) was observed in 57 pts (91.9%) after a median time of 6 months (range 2–72); 5 pts (8.1%) who failed to respond were referred to other treatments. With a median follow-up time of 76 months (range 12–162) the histological remission persists in 27/57 pts (47,4%); 21/57 pts (36.8%) have a continuous histological score fluctuation (from 0 to 4); 8/57 (14%) pts had an histological relapse (score 5) after a median time of 12 months (range 6–48) without Hp reinfection and 6 of them had a second spontaneous histological remission. The OS at 76 months is 93%. Only one patient died for an high grade gastric MALT lymphoma transformation. Conclusion: the majority of pts with gastric MALT lymphoma have a favourable long term outcome, independently of the pathological remission; eradication therapy may offer a real chance of cure. Watch and wait policy in agreement pts who failed to respond could be considered an option outside of clinical trial. No significant financial relationships to disclose.
Bortezomib is active in Waldenstrom’s Macroglobulinemia (WM)—Results of a National Cancer Institute of Canada (NCIC) phase II study in previously untreated or treated WM
Authors: Chen C. I. , Kouroukis T. , White D. , Voralia M. , Stadtmauer E. , Wright J. , Powers J. , Eisenhauer E. 
Published: March 2020

7543 Background: WM is a B cell lymphoma characterized by a serum monoclonal IgM and marrow infiltration by lymphoplasmacytoid cells. Bortezomib is a proteasome inhibitor active in myeloma and other hematologic malignancies. In this 2-stage study, 27 WM pts received single agent bortezomib with RR as primary endpoint. Methods: Eligibility: symptomatic WM (Hb <110 g/L; lymphadenopathy; organomegaly; or hyperviscosity); ≤2 prior chemo regimens (± rituximab). Bortezomib 1.3 mg/m2 IV given d1, 4, 8, 11 on a 21d cycle until PD or 2 cycles beyond CR/SD. Nodal disease was included in response criteria (2nd International WM Workshop). Results: Median age 65 (46–87), M:F 14:13, no prior therapy 11 (44%). At entry, median IgM 38 g/L (11.2–83.3); median Hb 108 g/L (63–142); 18 (66%) with nodal disease on CT. At a median of 6 cycles (2–35), 11/27 (41%) patients had ≥50% decrease in IgM alone plus 10 (37%) minor responses (25–49% decrease). Using IgM + nodal criteria: 1 CR, 5 PR (≥50% decrease in IgM and bidimensional disease), 20 SD, 1 PD = overall RR 22% (95% CI 8.6–42.2%). IgM responses were prompt (median 2 cycles; range 1–8) with nodal responses lagging (median 4 cycles). Hb increased by ≥10g/L in 18 pts (66%). Bortezomib was well-tolerated with most non-hematologic toxicities Gr 1–2: fatigue (74%), nausea (63%), myalgias (51%), non-neutropenic infections (48%), diarrhea (44%), constipation (44%). 18 pts (66%) developed neuropathy (sensory): typical onset 2–4 cycles; Gr 3 in 5 pts; 15/18 (83%) improving ≥1 grade (11 complete) in 2–13 mo. Gr 3 myalgias in 2 pts resolved in <1 mo. Gr 3–4 thrombocytopenia (30%) and neutropenia (18%) led to 12 missed doses, 1 dose reduction. Conclusions: Bortezomib is active in WM with 78% pts with ≥25% fall in IgM, 41% with IgM response criteria of ≥50% decrease, 22% with composite nodal/IgM responses. Despite prompt IgM and hematologic improvement, decrease in nodal disease is slow, reflected in overall responses lower than IgM alone. Although bortezomib is generally well-tolerated, neuropathy is common but reversible. Bortezomib combinations with conventional cytotoxic or targeted agents warrant further study in WM. This is a NCIC CTG study with a grant from NCIC and funds from Canadian Cancer Society. [Table: see text]