bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of melphalan-prednisone-thalidomide (MP-T) to melphalan-prednisone (MP) in patients 75 years of age or older with untreated multiple myeloma (MM). Preliminary results of the randomized, double-blind, placebo controlled IFM 01–01 trial
Authors: Hulin C. , Virion J. , Leleu X. , Rodon P. , Pegourie B. , Benboubker L. , Doyen C. , Dib M. , Guillerm G. , Moreau P. 
Published: March 2020

8001 Background: The MP-T combination has been shown to be the standard treatment in newly diagnosed MM patients (pts) aged 65 to 75 years (Facon et al; JCO 2006; 24, A1). However, no specific therapeutic recommendation exists for pts older than 75 years regarding the benefit of adding Thalidomide to MP. Methods: The IFM 01–01 trial was initiated in 04/2002. Patients > 75 years with untreated MM were randomized to receive MP (Melphalan 0.2mg/kg/d + Prednisone 2 mg/kg/d day1–4, 12 courses at 6-weeks intervals) + placebo (MP-placebo) vs MP + daily Thalidomide 100mg/d (MP-T). No anti-VTE prophylaxis was given. The primary end-point was overall survival (OS). Secondary end points were progression-free survival (PFS), response to treatment and toxicity. A first interim analysis was performed after the inclusion of 150 patients and a data safety monitoring board recommended a second analysis after the accrual of 200 patients. We here present the preliminary results of this analysis. Results: At the reference date of November 1, 2006, 232 pts were randomised. In all, 200 pts were analysed (100 per group), with 33.5% of pts >80 years (median age, 78.4 years). There were no differences between the 2 groups regarding baseline characteristics. Data were analysed on an intent-to-treat basis. After the completion of therapy the rates of partial response and very good partial response were 31% and 8% respectively with MP-placebo vs 61% and 22% respectively with MP-T. The median PFS time was 19 months (95%-CI 14.6–21.5) with MP-placebo vs 24.1 months (95%-CI 19.4–29.7) with MP-T (p=0.004 log-rank test). In the MP-T arm, 43/100 pts stopped treatment due to toxicity (10 due to neuropathy) versus 11/100 in the MP-placebo arm. Toxicity (Grade 2–4) included peripheral neuropathy (18%), somnolence (7%) and DVT (7%) with MP-T, vs 6%, 6% and 1% respectively, with MP-placebo. Final results including OS data will be presented at the meeting. Conclusion: MPT is an effective combination with acceptable toxicity in patients with MM = 75 years of age, with a significant improvement in PFS. No significant financial relationships to disclose.
Bortezomib (BTZ) prior to and as maintenance therapy after autologous stem cell transplant (ASCT) in multiple myeloma (MM): Long-term follow-up of a phase II study
Authors: Goyal S. D. , Uy G. , DiPersio J. F. , Vij R. 
Published: March 2020

8044 Background: BTZ and immunomodulatory drugs have emerged as active therapeutic options for MM. However, the optimal method of incorporating these agents in the ASCT paradigm remains unclear. Data is available on thalidomide induction and post ASCT maintenance therapy. However, there are no published data on BTZ used in this manner. Methods: Following induction therapy, BTZ 1.3 mg/m2 was administered on d 1, 4, 8, and 11 q21d × 2 cycles. ASCT with melphalan 200mg/m2 was performed using G-CSF mobilized PBSC. Maintenance BTZ 1.3 mg/m2/d was administered weekly for 4 of 5 weeks × 6 cycles starting 90–120 days post-transplant. Results: 39 patients completed pre-transplant BTZ: 23M/16F, median age 56 years (range 38–69), IgG (28), IgA (10), light chain only (1), Durie-Salmon stage I (1) II (12) III (26), induction anthracycline/thalidomide-based regimen (37). 37 patients underwent ASCT. Pre-transplant treatment with BTZ did not adversely affect stem cell yield or engraftment (Uy et al, Blood, 2005;106(11): abstr 2926). The ORR /CR+VGPR were 92%/53% at d90–120 post-transplant. With a median follow up of 897 days, the median PFS was 806 days and Kaplan-Meier estimate of 3-year PFS is 41% (95% CI, 31–63%). Median OS has not been reached with 3-year OS estimate of 79% (95%CI, 63–94%). 14/39 (36%) patients experienced varicella zoster virus (VZV) reactivation at a median of 200 days post-enrollment. 12/39 patients had grade (Gr) 1 neuropathy at enrollment. Gr 3/4 neuropathy emerged in 2 patients preventing initiation of maintenance BTZ. Gr 3/4 neuropathy emerged in 3 patients during maintenance BTZ requiring drug discontinuation in two and dose reduction in one patient. No grade 3/4 hematologic toxicity was observed during maintenance BTZ. Conclusions: This is the first trial reporting on sequential administration of BTZ prior to and as maintenance therapy post ASCT in MM. Impressive CR/VGPR, PFS and OS were observed and a high rate of VZV reactivation was seen. No significant financial relationships to disclose.
The benefit of reduced intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) as salvage treatment for relapsing multiple myeloma (MM)
Authors: Mohty M. , De Lavallade H. , Chabannon C. , Stoppa A. , Faucher C. , El-Cheikh J. , Furst S. , Gastaut J. , Blaise D. 
Published: March 2020

8045 Background: The role of RIC allo-SCT in MM is still controversial. This single centre study aimed to evaluate RIC allo- SCT for relapsed MM, using a genetic randomization through a donor vs. no donor comparison. Methods: Between 2002 and 2005, 32 patients with relapsed or refractory MM, and with an identified sibling, were referred to our centre for HLA typing. In all, 19 patients (59%; donor group) had an HLA-identical sibling donor, while the remaining 13 pts (41%; no donor group) had no HLA-identical sibling donor. There were no significant differences between these two groups that were comparable as for demographic, disease and prognosis factors. All pts had previously failed auto-SCT. Results: Among the 19 pts from the donor group, 18 (95%) could proceed to allo-SCT. With a median overall FU of 36 m., 11 patients (85%; 95%CI: 54–98%) from the no donor group had disease progression despite salvage therapy, and only 6 of them are still alive, of whom 5 (80%) in progressive disease at last FU. In contrast, only 5 pts (28%;P=0.001) from the donor group progressed after RIC allo-SCT. In the RIC allo-SCT group, 10 pts (56%;95%CI;33–79%) are still alive, with 4 pts being in CR, and 5 in PR or VGPR. Only one patient is currently experiencing disease progression and receiving salvage therapy. Interestingly, 11 pts (61%;95%CI,39–83%) from the RIC allo-SCT group showed objective disease response, usually concurrent to chronic GVHD. In all, 6 pts died from TRM for an overall incidence of TRM of 33% (95%CI,11–55%) in this population of heavily pretreated and relapsed or refractory MM population. In an intention-to- treat analysis, the KM estimate of progression-free survival was significantly higher in the donor group as compared to the no donor group (P=0.01; 46% vs. 8% at 3 y.). Conclusions: RIC allo-SCT from an HLA-identical sibling is a feasible and potential therapy that should be proposed for refractory or relapsed MM, since a potent graft-vs. -MM effect can be induced despite heavy pretreatments, allowing for significantly longer PFS. Also, the latter results are expected to be further improved with the systematic and early use of maintenance therapies after RIC allo-SCT. No significant financial relationships to disclose.
A feasibility study of VcR-CVAD with maintenance rituximab for untreated mantle cell lymphoma
Authors: Kahl B. S. , Peterson C. , Blank J. , McFarland T. , Huie M. , Eickhoff J. , Werndli J. , Callander N. , Myers T. 
Published: March 2020

8062 Introduction: Novel treatment strategies are needed for Mantle Cell Lymphoma (MCL). We have published the results of a study using a modified R-hyperCVAD induction followed by maintenance rituximab (Kahl et al, Ann Oncol 2006). This induction strategy yielded a complete response (CR) rate of 64%. Given the promising activity of bortezomib (VELCADER) in relapsed MCL, we hypothesized that the incorporation of VELCADE (Vc) into the induction regimen would improve the CR rate. Methods: Eligible patients have histologically confirmed MCL, PS 0–2, and adequate end organ function. VcR-CVAD regimen: Velcade 1.3 mg/m2 days 1 and 4, rituximab 375 mg/m2 IV day 1, cyclophosphamide 300 mg/m2 IV over 3 hrs q 12 hrs X 6 doses days 1–3, doxorubicin 50 mg/m2 CI over days 1–2, vincristine 2 mg IV day 3, dexamethasone 40 mg po days 1–4. The first 7 patients received a Vc dose of 1.5mg/m2 on days 1 and 4 but this was modified to 1.3 mg/m2 due to excessive peripheral neuropathy (PN). Cycles are repeated every 21 days for 6 cycles and all patients receive G-CSF cytokine support. Patients achieving at least a PR receive maintenance rituximab therapy. Results: Currently 15 patients are enrolled with 13 having completed the VcR-CVAD induction and two in active treatment. Patient characteristics: 11M, 4F, median age 64 (49–73), and 13/15 stage IV. Of the 13 assessable patients, one experienced PD during induction therapy and expired. The remaining 12 patients have all achieved a complete response (CR rate 92%) and are currently receiving maintenance rituximab. The major toxicities of this treatment regimen are painful PN and expected hematological toxicity. Five/seven patients at 1.5 mg/m2 and 3/6 patients at 1.3 mg/m2 experienced grade 3–4 PN. All PN eventually resolved to grade 1- 2 and resolved faster in the patients receiving 1.3 mg/m2. Conclusion: The VcR-CVAD induction has produced high overall and complete response rates (92%) in a very representative MCL patient population. A Vc dose of 1.3 mg/m2 is better tolerated than a dose of 1.5 mg/m2. However, PN remains an issue and the final cohort in this feasibility study will receive a vincristine dose of 1 mg. The encouraging response rates noted in this pilot study provide the basis for ECOG protocol 1405, which will test this regimen in a cooperative group setting. No significant financial relationships to disclose.
Rituximab maintenance therapy (RM) for relapsed/refractory follicular lymphoma (FL): Long-term economic impact in the French setting
Authors: Brice P. , Miadi-Fargier H. , Le Pen C. , Pacull A. , Coudray-Omnes C. , Deconinck E. 
Published: March 2020

8076 Background: FL in advanced stages is a life-threatening chronic disease. As recently demonstrated in the pivotal trial EORTC20981, RM significantly prolongs both progression free survival (PFS) and overall survival (OS) in relapsed/refractory FL patients responding to an induction treatment. Beyond these clinical benefits, the study objective was to assess, from the French Sickness Funds perspective, long-term costs and cost-effectiveness of RM after induction therapy versus current standard practice (observation). Methods: A lifetime transition model (30-years time horizon) with 3 health states (progression free, progressive disease and death) was developed comparing RM and observation (Obs). PFS and OS in the health states transition model were derived from the EORTC20981 trial with a median follow-up of 28 months. PFS and the OS benefits of RM therapy were conservatively assumed to last only 5 years. Standard French costs (2006 national tariffs) were applied to resources estimated from a prescription observational study, expert opinion and bibliography (in case of maintenance: acquisition and administration of RM, grade 3–4 adverse events, follow-up and in case of relapse: pre-treatment check- up, chemotherapy, radiotherapy, stem cell transplantation, adverse events, follow-up and supportive care). Costs were discounted at 3% and sensitivity analyses were performed. Results: RM is effective in the management of relapsed/resistant FL with more than one year of benefit in terms of survival. Patients receiving RM had a longer life expectancy than those with Obs (6.60 versus 5.41 years). Overall lifetime average costs were €71,314 and €62,251 respectively for RM and Obs. Incremental cost-effectiveness ratio (ICER) was €7,612 per life year gained, varying from €7,154 to €8,847 in one-way sensitivity analysis. This study did not include palliative care and productivity costs. As the relapse rate is lower in the RM group, those limitations are conservative. Conclusions: The economic assessment shows that RM is a cost-effective strategy in the management of relapsed/refractory FL in France with an ICER largely below the threshold commonly cited in such analysis. No significant financial relationships to disclose.
Clinical significance of diffusion-weighted whole body magnetic resonance imaging with background body signal suppression (DWIBS) as a staging procedure for lymphoma patients in comparison with FDG-PET
Authors: Itoyama T. , Shibuya T. , Koga T. , Kitagawa M. , Yoshida T. , Kobayashi H. , Utsunomiya A. , Ochiai R. 
Published: March 2020

8084 Background: FDG-PET is thought to be an important staging tool in lymphomas. However, high cost and exposure to radioactive agents are of disadvantage. Diffusion weighted whole body magnetic resonance imaging with background body signal suppression (DWIBS) is recently reported to be a new way of magnetic resonance imaging which can make FDG-PET-like imaging possible to detect tumors (Takahara et al; Radiation Medicine 22: 275–282, 2004). This study is aimed to compare accuracy and clinical significance of DWIBS to FDG - PET. Methods: We examined 19 lymphoma (Ly) patients (pts) by using both DWIBS and FDG -PET at the time of diagnosis before therapy. There were follicular Ly in 3 pts, nodal marginal zone Ly in 1, diffuse large B-cell Ly in 9 including primary stomach Ly in 2, peripheral T -cell Ly in 4, and MALT Ly of stomach (GI-MALT) in 2. DWIBS was performed with a 1.5 -Tesla system as previously reported (Ochiai et al; Nichidoku -Iho 50: 86–98, 2005). Clinical staging was made according to the Ann Arbor classification. Results: Both DWIBS and FDG -PET had positive findings in 18 of 19 pts except for a case of GI -MALT. In nodal lesions, DWIBS was positive in 16 pts at 66 sites compared to 16 pts at 68 sites with FDG -PET. DWIBS was negative in 3 pts at 5 sites in spleen, hilar and mediastinal lymphnodes where positive in FDG -PET. DWIBS was positive in 2 pts at 4 sites in iliac and inguinal lymphnodes that are negative in FDG -PET. In extranodal lesions, DWIBS was positive in 12 pts at 17 sites as compared to 12 pts at 18 sites with FDG -PET. Involvement of bone and stomach were equally identified at 8 sites. DWIBS was negative in 2 pts at 2 sites in liver and pleura with FDG -PET positive. Small skin lesions were clearly identified on DWIBS. Discordance of clinical staging was not observed between DWIBS and FDG -PET. Conclusions: Although some discrepancy was seen between DWIBS and FDG -PET, there was no disadvantage of DWIBS compared to FDG -PET. Furthermore, DWIBS has no risk of radiation exposure and is even advantageous to detect lesions with FDG -PET negative. We conclude DWIBS is a new useful tool to assess tumor spread in lymphomas. No significant financial relationships to disclose.
Near absence of IL-15R-alpha T-cells in EBV-associated Hodgkin lymphoma patients
Authors: Baiocchi O. C. , Lin L. , Yang J. , Lemas M. V. , Post L. , Mueller N. , Ambinder R. F. 
Published: March 2020

8087 Background: Epstein-Barr virus (EBV) (+) Hodgkin's lymphoma (HL) has been linked to acute infectious mononucleosis (AIM). EBV-associated AIM was recently reported (Sauce et al, Blood 2006, 108: 11) to be associated with a long lasting immunologic scar (near complete absence of IL-15 receptor alpha (IL-15Ra expression on T cells in peripheral blood mononuclear cells (PBMC)). We sought to confirm the scar observation and to determine whether such a scar might also be characteristic of EBV (+) HL patients. Methods: PBMCs from 5 donors with history of AIM (3 months to 4 years before), 10 EBV-seropositive donors without history of AIM, 10 EBV-seronegative donors, 22 HL patients with EBV (+) tumors and 29 HL patients with EBV (-) tumors were assayed to determine IL-15Ra expression on CD3/CD8+ cells using a FACScalibur flow cytometer. Results: IL-15Ra expression in healthy donors with history of AIM [mean: 2.9% (1.5–6.5%)] was much lower than in those without history of AIM [mean: 83% (65–98%)] (p = 0.001). Expression did not differ between healthy EBV-seropositive donors without history of AIM [mean: 82% (65–95%)] and healthy EBV-seronegative donors [mean: 89% (82–98%)] (p = 0.32). Expression was markedly different between EBV (-) HL [mean: 82% (72–99%)] and EBV (+) HL patients [mean: 3.2% (1.1–7.1%)] [p = 0.001, 95% CI(10.3–32.1)]. No difference was found when age, time blood was drawn (pre or post-treatment), disease stage and histological subtype were compared. This IL- 15Ra deficit was seen in patients before and more than one year after standard therapy. Conclusions: This study confirms the virtual absence of IL-15Ra expression in lymphocytes from patients with history of AIM. That observation is now extended to include patients with EBV (+) HL at presentation and in remission. Whether this deficit contributes to the pathogenesis of EBV (+) associated HL remains to be determined. No significant financial relationships to disclose.
Cost-effectiveness of rituximab maintenance therapy for patients with follicular lymphoma: The Spanish perspective
Authors: Gómez Codina J. , Provencio M. , Rueda A. , Capote F. , Carbonell F. , Conde E. , Fernandez Rañada J. , Giraldo P. , Rios E. , Varela C. 
Published: March 2020

8092 Background: In patients with relapsed or refractory follicular lymphoma (FL) who attain a response with either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone or Rituximab + CHOP, maintenance treatment with Rituximab has shown to significantly improve overall survival (OS) (85% at 3 years vs. 77%, p=0.011) and progression free survival (PFS) (51,5 vs. 14.9 months, p<0.001) as compared to observation alone (OA). We analyzed the cost-effectiveness, from a Spanish perspective, of Rituximab maintenance therapy (375mg/m2 every 3 months until progression or for 2 years) versus OA according to the population and data described for the European Organization for Research Treatment of Cancer (EORTC) 20981 study (van Oers MHJ Blood 2006). Methods: Incremental cost-effectiveness was assessed through a deterministic, three health states model (disease-free, progression and death) transition model. Base case model: PFS and OS were extrapolated from EORTC 20981 data using a Weibull distribution, Rituximab maintenance benefit was assumed to last 5 years, 10 years time horizon, 3.5% discount rate on costs and benefits, and Spanish National Health Service perspective (direct costs only). Resource use was estimated from a Spanish expert panel and EORTC 20981 study. Unit costs were obtained from local databases (May 2006 €). Health states utility values were derived from an ad hoc study. Sensitivity analyses were performed for all mentioned variables. Results: For the base case, more quality-adjusted life years (QALY), life-years (LY) and progression-free survival years per patient on maintenance therapy were obtained versus OA (incremental values of 0.85, 0.94 and 1.46, respectively). Total cost per patient was higher with Rituximab than with OA (+8,026€). Incremental cost per QALY gained was 9,358€, with a cost per LY gained of 8.493€ and a cost per PFS year gained of 5,485€. In the sensitivity analysis, values ranged between 7.263€ and 22.160€ per QALY gained. Conclusions: This study confirms that in patients with relapsed /refractory FL who attain a response with further therapy, maintenance treatment with Rituximab compared to observation alone is cost-effective. No significant financial relationships to disclose.
H pylori-positive gastric diffuse large B-cell lymphomas are potentially curable by H pylori eradication therapy
Authors: Kuo S. H. , Chen L. T. , Wu M. S. , Lin C. W. , Kuo K. T. , Wang H. P. , Hsu P. N. , Lin J. T. , Cheng A. L. 
Published: March 2020

8093 Background: We have recently demonstrated that early-stage gastric diffuse large B-cell lymphomas (DLBCLs) with MALToma, as well as their MALToma counterparts, may respond to H pylori eradication therapy (HPET). The present study was conducted to evaluate the effect of HPET in stage IE gastric DLBCLs without MALToma. Methods: Seven patients (4 men and 3 women; age range, 35 to 83 years) with H pylori infection and stage IE gastric DLBCL without MALToma received HPET as first-line treatment from June 2002 through May 2006. Additional immunohistochemical reaction with anticytokeratin was performed to exclude lymphoepithelial lesions (minimal MALToma components) in DLBCL. All patients received intensive endoscopic follow-up examinations with biopsy to evaluate tumor response. Patients with significant improvement of gross lesions that accompanied regression of tumor cells were followed up without additional treatment. Patients without significant improvement were immediately referred to systemic chemotherapy. Tumors that resolved to Wotherspoon grade 2 or less after successful HPET were considered as complete histologic remission. Results: Successful HPET was achieved in all patients. There were 5 patients with complete histologic remission. The complete remission rate was 71.4% (95% confidence interval, 45.1% to 97.7%). The median duration between HPET and complete histologic remission was 2.6 months (range, 1.1 to 5.7 months). At a median follow-up of 24.2 months (range, 5.7 to 56.8 months), all patients with complete histologic remission after HPET were alive and free of lymphoma. Conclusions: A substantial portion of early-stage gastric DLBCLs without MALToma remain H pylori-dependent and can potentially be cured by HPET. No significant financial relationships to disclose.
Alemtuzumab in clinical practice: A British Columbia experience
Authors: Hui D. , Lam W. , Toze C. , Delorme M. , Noble M. , Klimo P. , Sutherland J. , Gill K. , Connors J. , Sehn L. 
Published: March 2020

8098 Background: Limited information is available on alemtuzumab in the non-clinical trial setting. We evaluated its efficacy and safety in 42 consecutive unselected patients who received alemtuzumab monotherapy in British Columbia between October 2002 and August 2006. Methods: Information on patient demographics, baseline clinical and pathologic characteristics, dose and schedule of treatment, clinical response, survival, and toxicities associated with alemtuzumab were collected retrospectively. Results: Thirty-nine of 42 patients had chronic lymphocytic leukemia, 2 had mycosis fungoides, and 1 had T-cell post-transplant lymphoproliferative disorder. In contrast to previous reports, 42% were treated by community practitioners and 83% received alemtuzumab subcutaneously. The median time from diagnosis to alemtuzumab was 58 months, with a median age of 63 years at alemtuzumab treatment. Patients received a median of 4 treatments prior to starting alemtuzumab. One of 42 patients (2%) achieved a complete response, 20 (48%) achieved a partial response, 13 (31%) had stable disease, and 4 (10%) had progressive disease. The median post-alemtuzumab overall survival was 15.1 months and the median progression-free survival was 5.4 months. Response to alemtuzumab correlated with an increased progression- free survival (11 months versus 3.6 months, p=0.001) and time to next treatment (15.7 months versus 5.4 months, p=0.004). Significant adverse events included grade 3 or 4 neutropenia (75%) or thrombocytopenia (42%), infections (54%) including CMV reactivation (6%), and death (12%). Patients who received alemtuzumab in the community setting had a higher incidence of febrile neutropenia (p=0.05) and infection (p=0.03) compared to academic centres, although no difference in overall survival was noted. Conclusion: Alemtuzumab can be safely administered in a wide variety of clinical settings, including community practice, and is associated with a high level of activity. No significant financial relationships to disclose.