Randomized Comparison of Cladribine Containing Regimens and COP in Previously Untreated Patients with Small Lymphocytic, Marginal Zone and Follicular Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4739-4739
Author(s):  
Ewa Kalinka ◽  
Jaroslaw Wajs ◽  
Kazimierz Sulek ◽  
Tadeusz Robak ◽  
Maria Blasinska-Morawiec ◽  
...  
Keyword(s):  
Side Effects ◽  
Overall Response Rate ◽  
Marginal Zone ◽  
Response Rate ◽  
Low Grade ◽  
Front Line ◽  
Histological Subtypes ◽  
First Line ◽  
To Receive

Abstract The aim of the study was to comparatively assess first-line treatment with cladribine alone or in combination with cyclophosphamide (CCR, cladribine-containing regimens) and COP (cyclophosphamide, vincristine, prednisone) in different subtypes of low-grade lymphoma. End points were complete remission (CR), overall response rate (ORR), incidence of chemotherapy-related side effects as well as freedom from progression (FFP) and overall survival (OS). From June’2000 to June’2005, 178 previously untreated patients (pts) were randomly allocated to receive 6 monthly courses of either CCR or COP in 17 centers in Poland. This analysis included 107 pts who have completed scheduled chemotherapy, including 45 pts with small lymphocytic (SLL, median age=64 years), 26 marginal zone (MZL, median age=58 years) and 36 follicular (FL, median age=65 years) lymphoma. Compared to COP, CCR induced higher CR rates in all treated groups (65% vs 15%, p=.005; 57% vs 10%, p=.02; 58% vs 12%, p=.03, respectively) but differences in ORR were not significant (92% vs 69%; 92% vs 60%; 79% vs 62%, respectively). Incidence of side effects did not differ significantly in CCR- as compared to COP-treated pts, e.i. infections (10% vs 7%; 14% vs 20%; 15% vs 0%, respectively), myelosuppression (31% vs 7%; 21% vs 20%; 30% vs 0%, respectively), and non-hematological adverse events (10% vs 14%; 7% vs 30%; 7% vs 22%, respectively). With a median follow-up of 12 months, median FFP was superior in CCR- as compared to COP-treated treated pts with SLL (43 vs 12 months, log-rank p<.03) or MZL (37 vs 7 months, log-rank p<.03) but not with FL (17 vs 22 months). Although the median OS has not been reached in any of the histological group so far, no difference in its duration is detected between CCR- or COP-treated pts. In summary, for pts with SLL, MZL and FL, first-line CCR regimens provided better CR and similar toxicity rates as compared to COP, which translated into longer FFP in SLL and MZL but not in FL pts. Although these results warrant larger number of pts and longer follow-up, they might suggest the choice of different front-line chemotherapy with or without immunotherapy in particular histological subtypes of low-grade lymphoma.

Decitabine Low-Dose Schedule (100 mg/m2/Course) in Myelodysplastic Syndrome (MDS). Comparison of 3 Different Dose Schedules.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2522-2522 ◽  
Author(s):  
Hagop Kantarjian ◽  
Susan O’Brien ◽  
Francis Giles ◽  
Farhad Ravandi-Kashani ◽  
Stefan Faderl ◽  
...  
Keyword(s):  
Low Dose ◽  
Overall Response Rate ◽  
Response Rate ◽  
Optimal Schedule ◽  
Dose Schedule ◽  
Overall Response ◽  
Transfusion Independence ◽  
Secondary Mds ◽  
To Receive

Abstract Background Decitabine (DAC), a hypomethylating agent, has shown activity in MDS. DAC 150 mg/m2 by continuous infusion has been associated with CR rates of 10% to 20%. We investigated optimizing the dose schedule of DAC in MDS. Study Group and Methods Patients (pts) with IPSS intermediate 1–2 & high risk MDS were randomized to one of 3 schedules of DAC: 1) 20 mg/m2 IV over 1 hour daily x 5; 2) 10 mg/m2 IV over 1 hour daily x 10; or 3)10 mg/m2 subcutaneously (SQ) BID x 5. A total of 95 pts are to be treated; Bayesian randomization is implemented based on CR rates. Courses were given every 28 days. Delays to allow counts recovery were permitted every 3 courses, or if myelosuppression without disease, or severe myelosuppression complications. Pts were allowed to receive erythropoietin 40,000 units weekly for anemia, or GCSF if needed. Response criteria for CR & PR were as for AML (PR requiring also ↓ blasts by &gt;50%). Clinical benefit (CB) referred to one or more of: platelets î by ≥ 50% and &gt;30 x 109/L, or granulocytes increase by ≥ 100% and to &gt;109/L, or hemoglobin î by ≥ 2 g/dl or transfusion independence, or splenomegaly ↓ by 50% or more, or monocytes ↓ by 50% or more (pretreatment &gt;5 x 109/L). Results 92 pts have been treated; median age 65 (31–90) yrs; 66% &gt;60 yrs old. IPSS: intermediate-1 25%; intermediate-2 38%; high 19%; CMML 17% Cytogenetic abnormalities 57%; secondary MDS 17%; marrow blasts &gt; 10% in 31%. 27 pts had prior erythropoietin; 17 had prior GCSF; 22 had other prior therapies. Presently, 89 pts have received 1 course. Results: 32 CR (36%); 7 PR (8%); 13 marrow CR + CB (15%); 16 CB (18%); overall response 68/89=76%. Median courses to CR 3 (range 1 to 6). Median follow-up of 9 months; 48 pts continue on DAC. Compared with a 114 pts with MDS who received intensive chemotherapy (2000–2004), CR rate was lower with DAC (36% vs. 45%), overall response rate was favorable; 6-week mortality was lower with DAC (1% vs. 21%); and estimated survival favorable (p = 0.00007). CR rates by schedule: 5 days IV 24/58 (41%); 5 days SQ 4/14 (28%); 10 day IV 4/17 (24%). There was more myelosuppression with 10 day IV. After 55 patients were randomized, the 5 day IV arm was determined statistically superior, therefore, remaining patients were not randomized, but were treated with 5 days IV therapy. Conclusions DAC has significant anti-MDS activity; 2) optimal schedule: 20 mg/m2 IV over 1 hour daily x 5; 3) timely repeated courses needed for optimal response.

Pemetrexed (MTA) and carboplatin (CBDCA) in the treatment of advanced pleural mesothelioma (MPM)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7093-7093 ◽  
Author(s):  
B. Castagneto ◽  
M. Mencoboni ◽  
D. Degiovanni ◽  
A. Muzio ◽  
L. Giaretto ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Entire Group ◽  
Hematologic Toxicity ◽  
First Line ◽  
Ecog Performance Status ◽  
Grade 3

7093 Background: Aim of this study was to evaluate the activity and toxicity of MTA and CBDCA combination as first line chemotherapy in advanced MPM. Methods: Chemonaive patients (pts) with histologically proven, an ECOG performance status (PS) 0–2, and measurable advanced MPM were considered. The schedule of administration was: pemetrexed 500 mg/m2 in combination with CBDA AUC 5, once every 21 days for 8 cycles. Results: From July 2003 to March 2005 76 pts (54 male and 22 female) have been treated with this combination chemotherapy. Median age was 62.7 years (range 40–70); median PS 0 (range 0–3); epithelial histologic findings were in 57 (75%), mixed in 13 (17.1%), sarcomatous in 3 (3.9%), and unspecified in 3 (3.9%) pts. A total of 537 cycles was administered (median 7, range 1 to 13). Grade 3 hematologic toxicity according to WHO criteria was seen in 43 (56.6%) pts (neutropenia in 30, thrombocytopenia in 8, and anemia in 5); grade 4 hematologic toxicity in 5 (6.6%) pts. The most common nonhematologic events were grade 3 nausea/vomiting in 10 (13.1%), and fever in 4 (5.3%) pts. 74 pts were evaluable for clinical response. There were 16 (21.%) partial responses (PR) and 3 (3.9%) complete responses (CR), for an overall response rate of 23.9%. 29 (38.2%) pts reported stable disease (SD). The overall survival was considered from date of diagnosis to date of death from any cause or to date of last follow-up. The median survival time for the entire group was estimated at 23 months. Conclusions: The results of this phase II study indicate that, at this dose and schedule, the combination of CBDCA and MTA is moderately active and that the profile of toxicity is acceptable in pts with advanced MPM. No significant financial relationships to disclose.

scholarly journals Rituximab as Single Agent in Primary MALT Lymphoma of the Ocular Adnexa

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Ombretta Annibali ◽  
Francesca Chiodi ◽  
Chiara Sarlo ◽  
Magdalena Cortes ◽  
Francesco M. Quaranta-Leoni ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Line Treatment ◽  
First Line ◽  
Indolent Disease ◽  
Anti Cd20 ◽  
First Line Treatment

Ocular Adnexal Lymphomas are the first cause of primary ocular malignancies, and among them the most common are MALT Ocular Adnexal Lymphomas. Recently systemic immunotherapy with anti-CD20 monoclonal antibody has been investigated as first-line treatment; however, the optimal management for MALT Ocular Adnexal Lymphomas is still unknown. The present study evaluated retrospectively the outcome of seven consecutive patients with primary MALT Ocular Adnexal Lymphomas, of whom six were treated with single agent Rituximab. All patients received 6 cycles of Rituximab 375 mg/mq every 3 weeks intravenously. The overall response rate was 100%; four patients (67%) achieved a Complete Remission, and two (33%) achieved a partial response. In four patients an additional Rituximab maintenance every 2-3 months was given for two years. After a median follow-up of 29 months (range 8–34), no recurrences were observed, without of therapy- or disease-related severe adverse events. None of the patients needed additional radiotherapy or other treatments. Rituximab as a single agent is highly effective and tolerable in first-line treatment of primary MALT Ocular adnexal Lymphomas. Furthermore, durable responses are achievable with the same-agent maintenance. Rituximab can be considered the agent of choice in the management of an indolent disease in whom the “quality of life” matter is of primary importance.

scholarly journals Combining 308-monochromatic excimer phototherapy with monthly IM triamcinolone acetonide for the treatment of resistant alopecia totalis

2021 ◽  
pp. 37
Author(s):  
Keyword(s):  
General Practice ◽  
Triamcinolone Acetonide ◽  
Overall Response Rate ◽  
Response Rate ◽  
Young Patients ◽  
Interventional Study ◽  
Younger Patients ◽  
History Of ◽  
To Receive

Background: Treatment of resistant alopecia totalis AT is a major problem in general practice. Some studies reported the use of either excimer-308 or intra-muscular triamcinolone acetonide as a monotherapy, with conflicting results. Objective: To evaluate the therapeutic effect of combining 308-excimer phototherapy and intramuscular triamcinolone acetonide for the treatment of alopecia totalis. Methods and Material: Ten patients with alopecia totalis were evaluated in this prospective interventional study. All patients were assigned to receive the thera-peutic regimen that includes monthly IM triamcinolone acetonide (TAC) for a maximum of six pulses and twice-weekly excimer phototherapy for 24 sessions. Results: The overall response rate for this regimen was 90%, with four patients 40% achieving complete regrowth of hair (100%). Three patients have exhibited a satisfactory response (>70% regrowth). Unsatisfactory response ( >10-< 70% regrowth) was reported in two patients . Younger patients responded better, as did those with a shorter history of the disease P < 0.05. At follow-up, which continued for 8–12 months, recurrence was noted in two (22.2%) of the nine responders. Conclusions: Combining excimer phototherapy with triamcinolone acetonide showed a promising effect on resistant AT. This treatment modality was effective and well tolerated particularly in young patients.

scholarly journals Real-World Effectiveness and Safety of Eltrombopag in Patients with Aplastic Anemia: A Chinese Nationwide Survey

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5020-5020
Author(s):  
Wenrui Yang ◽  
Bing Han ◽  
Hong Chang ◽  
Bingyi Wu ◽  
Fankai Meng ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Real World ◽  
Overall Response Rate ◽  
Response Rate ◽  
Line Treatment ◽  
First Line ◽  
Overall Response ◽  
Treatment Naïve ◽  
First Line Treatment

Immunosuppressive therapy (IST) based on antithymoglobin (ATG) and cyclosporin (CsA) is the first-line treatment for severe aplastic anemia (SAA) patients who are unfit for transplantation,and the overall response rate (ORR) is about 70%.The utility of eltrombopag (EPAG),a TPO receptor agonist, achieved robust hematologic response in refractory and treatment-naïve SAA patients in clinical trials and some other studies. However, only a few data came from Asia countries where higher incidence of AA has been reported. A retrospective study on the use of EPAG in AA was conducted in mainland China. Aplastic anemia (transfusion dependent non-severe, severe, and very severe) patients who started eltrombopag before Feb 2019 and continued for at least 3 months either as first-line treatment or as rescue treatment, were enrolled. The maximum daily dosage of EPAG used continuously for at least 2 weeks is defined as the stable dosage. Response criteria were referred to that used in previous reports (Townsley DM, NEJM 2017; BCSH, BJH 2016). Fifty-six patients from eleven centers were enrolled in this study, including 26 males and 30 females at the median age of 39 (7-80) years. All patients were transfusion-dependent by the time of EPAG administration, and there were 14 VSAA, 24 SAA and 18 transfusion dependent non-severe aplastic anemia (TD-NSAA). Nineteen treatment-naïve patients received EPAG and IST (ATG+CsA, n=10; CsA/CsA+androgen, n=9) as first-line treatment. Thirty-seven patients were refractory to IST. Eltrombopag was administered at a median dose of 75 (25-150) mg per day for 7 (3-31) month. The median follow-up time was 9 (3-40) months. The overall response rate in patients receiving EPAG as first-line therapy was 78.9% (15/19), and most patients achieved complete response (CR) (10/15). Among the 10 patients receiving ATG+CsA, 6 patients achieved hematologic response (HR) at 3 months post-treatment, including 3 CR. Six patients were diagnosed as VSAA and three achieved HR. For the 9 patients treated with CsA/CsA+androgen, 8 achieved HR (88.9%) and 4 were CR (44.4%) at 3 months. By last follow-up, the cumulative HR rate was 70% in ATG+CsA group and 89% in CsA/CsA+ androgen group. Among the 14 responders, 11 patients receiving EPAG at a stable dosage ≤75mg/d and achieved HR at 3 months. The overall response rate in IST-refractory patients was 46% (17/37), with trilineage response in 27% patients at 3 months. For the 18 ATG+CsA refractory SAA patients,trilineage HR occurred in 4 patients (22.2%, 4/18), bi-lineage HR in one patient and single lineage HR in one patient. Thus, the total HR was 33.3% (6/18) at 3 months and increased to 44% (8/18) by last follow-up. Among the 19 CsA/CsA+ androgen refractory patients, 6 (31.5%, 6/19) achieved trilineage HR, one achieved bi-lineage HR and 4 achieved single lineage response. Total HR rate was 57.9% (11/19) at 3 months after EPAG initiation and 68% (13/19) by last follow-up, including 9 patients with trilineage HR. Among 17 responders, 13 received a stable EPAG dose of≤75mg/d. Most patients tolerated EPAG well. Adverse events occurred in 29 patients (52%) and most were mild to moderate, including gastrointestinal symptom (n=15, e.g. abdominal pain, nausea), impaired liver function (n=5), skin changes (n=7, e.g. skin pruritus and rash) and musculoskeletal pain (n=6), and venous thrombus (n=2). Eltrombopag dosage was reduced in 2 patients due to severe digestive symptoms at 100 mg/d and discontinued in one patient who suffered from upper limb venous thrombus. In conclusion, EPAG is effective and safe in treating Chinese AA patients at a daily dose of 75mg and less. The real-world result of EPAG in Chinese patients is similar to those reported in Western countries. Disclosures No relevant conflicts of interest to declare.

scholarly journals Fibroblast Growth Factor Receptor 2 Isoforms Detected via Novel RNA ISH as Predictive Biomarkers for Progestin Therapy in Atypical Hyperplasia and Low-Grade Endometrial Cancer

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1703
Author(s):  
Asmerom T. Sengal ◽  
Deborah Smith ◽  
Rebecca Rogers ◽  
Cameron E. Snell ◽  
Elizabeth D. Williams ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Overall Response Rate ◽  
Response Rate ◽  
Intrauterine Device ◽  
Predictive Biomarkers ◽  
Atypical Hyperplasia ◽  
Low Grade ◽  
Overall Response ◽  
Progestin Therapy

Women with atypical hyperplasia (AH) or well-differentiated early-stage endometrioid endometrial carcinoma (EEC) who wish to retain fertility and/or with comorbidities precluding surgery, are treated with progestin. Clinically approved predictive biomarkers for progestin therapy remain an unmet need. The objectives of this study were to document the overall response rate (ORR) of levonorgestrel intrauterine device (LNG-IUD) treatment, and determine the association of FGFR2b and FGFR2c expression with treatment outcome. BaseScope RNA ISH assay was utilized to detect expression of FGFR2b and FGFR2c mRNA in the diagnostic biopsies of 89 women (40 AH and 49 EEC) treated with LNG-IUD. Detailed clinical follow-up was available for 69 women which revealed an overall response rate (ORR) of 44% (30/69) with a higher ORR seen in AH (64%) compared to EEC (23%). The recurrence rate in women who initially responded to LNG-IUD was 10/30 (33.3%). RNA ISH was successful in 72 patients and showed FGFR2c expression in 12/72 (16.7%) samples. In the 59 women with detailed clinical follow-up and RNA-ISH data, women with tumours expressing FGFR2c were 5-times more likely to have treatment failure in both univariable (HR 5.08, p < 0.0001) and multivariable (HR 4.5, p < 0.002) Cox regression analyses. In conclusion, FGFR2c expression appears to be strongly associated with progestin treatment failure, albeit the OOR is lower in this cohort than previously reported. Future work to validate these findings in an independent multi-institutional cohort is needed.

Brentuximab Vedotin Followed By ABVD in Patients with Previously Untreated Hodgkin Lymphoma. a Pilot Phase II Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3088-3088 ◽  
Author(s):  
Pier Luigi Zinzani ◽  
Stefano Luminari ◽  
Francesco Merli ◽  
Emanuela Anna Pesce ◽  
Stephane Chauvie ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Complete Response ◽  
Pilot Phase ◽  
First Line ◽  
Overall Response

Abstract active and well tolerated single agent in the treatment of heavily pretreated Hodgkin lymphoma patients. In this pilot phase II study patients with previously untreated HL underwent sequential regimen consisting in 2 cycles of BV before doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) +/- radiotherapy (RT). The primary endpoint of the study was the response to BV assessed by positron emission tomography (PET) after the 2 cycles (PET2), defined as reduction of Deauville score or, in case of no change in Deauville score, as any reduction in standard uptake value (SUV) intensity compared to basal SUV. Between April and October 2013, 12 patients with a median age at diagnosis of 36 years (range, 19-70), 11 stage I-IIA and 1 stage IIIA, were enrolled. BV was administered as scheduled and at the full dose of 1.8 mg/kg in all patients. After the 2 cycles of BV, the overall response rate was 91%, comprising of ten (83%) complete responses and one (8%) partial metabolic response. The non responding patient had stage III and showed a new lesion at PET2. After ABVD +/- RT, the overall response rate was 100% with 11 complete responses and 1 partial response (converting from progression disease). At a median follow up of 8 months, all 11 patients are still in complete response, while the remaining one relapsed. During BV therapy, the only grade 3 adverse events were transient and asymptomatic increase in liver transaminases (n=3, 25%) and gamma glutamyl transpeptidase (n=2, 17%). During ABVD +/- RT grade III-IV neutropenia occurred in 9 (75%) patients. All toxicities were transient and resolved with growth factor support. Two cycles of BV as first line-treatment in limited stage HL induced an outstanding complete response rate with limited toxicity and reducing the need of chemotherapy. Waiting for a longer follow up to assess the duration of response, our data (sequential administration of immunotherapy and chemotherapy) should be considered the starting point for further studies in first line therapy for limited stage HL patients. Disclosures No relevant conflicts of interest to declare.

Intravenous Administration of Rituximab in the Treatment of Primary Cutaneous B-Cell Lymphomas (PCBCLs): A Retrospective Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5470-5470
Author(s):  
Giovangiacinto Paterno ◽  
Annagiulia Zizzari ◽  
Daniela Nasso ◽  
Lorenzo Tonialini ◽  
Cecilia Angeloni ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Marginal Zone ◽  
Response Rate ◽  
Conflicts Of Interest ◽  
Disease Free Survival ◽  
Front Line ◽  
Free Survival ◽  
Number Of Patients ◽  
Increased Risk ◽  
Disease Free

Abstract Introduction. Rituximab has been demonstrated to be effective either as intralesional or as systemic therapy in PCBCL, We report our experience in the treatment of PCBCL with intravenous Rituximab. P atients and Methods From February 1999 to February 2014 we treated 75 patients: 47 Follicle Center Lymphoma, 23 Marginal Zone Lymphoma, 5 Diffuse Large Lymphoma Leg type. The stage was T1 in 38 pts, T2 in 22 pts and T3 in 15 pts. In 24 patient prior treatment included: CHT (11), Radiotherapy (4), Surgery (4) or alpha2Interferon (IFN) (5). Rituximab at dosage of 375 mg/m2 for a minimum of 4 cycles, was administered alone (51 patients) or in association with CHT (13). RT (2) or IFN (3). Results. No patient presented adverse effects during the Rituximab infusion. A reduction of circulating B lymphocytes was observed for 11 months, on the average, without an increased risk of infections. No added toxicity was observed in patients treated with Rituximab plus CHT. Overall response rate was 97,3% (CR 82,6 %, PR 14,6 %). Five–years Overall Survival (OS) was 86,9% with Disease Free Survival of 57%. According to stage OS was in T1 94,3%, in T2 90,5%, in T3 73,6%. (T1+T2 vs T3: p<0,05). Conclusions. Rituximab is effective and safe in the treatment of PCBCL even in heavily-treated or elderly patients. In our patients only the stage of disease was significant for the prognosis. A higher number of patients are necessary to indicate Rituximab in biological and clinical subsets of patients as a front-line therapy. Disclosures No relevant conflicts of interest to declare.

scholarly journals Short Course of Bendamustine and Rituximab Followed By 90Y-Ibritumomab Tiuxetan in Patients with Chemotherapy-Naive Follicular Lymphoma (FOL-BRITe): Final Report of Response Rates and Progression Free Survival

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1793-1793 ◽  
Author(s):  
Cristiana A Costa ◽  
Bassem I Zaki ◽  
Stephanie P Yen ◽  
Eric S Winer ◽  
Helen Ryan ◽  
...  
Keyword(s):  
Partial Response ◽  
Follicular Lymphoma ◽  
Myeloid Leukemia ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Free Survival ◽  
To Receive

Abstract Background: Y90-Ibritumomab tiuxetan (90YIT) is approved for use for follicular lymphoma (FL) patients who have achieved a complete or partial response to frontline chemotherapy; however, its use after bendamustine and rituximab (BR) has not been reported. BR has proven to be a superior frontline therapy over R-CHOP in the treatment of FL and is a widely used initial treatment strategy. This analysis focuses on the long-term outcomes and safety of untreated follicular lymphoma patients treated with a short induction course of BR for 4 cycles followed by consolidation with 90YIT. Methods: Patients greater than 18 years with chemotherapy-naïve FL (grade 1-2 and 3a) requiring treatment were eligible. All patients had Stage II-IV disease and had adequate hematologic, liver, and renal function. Treatment consisted of an initial dose of rituximab 375 mg/m2. One week later, bendamustine 90 mg/m2 was administered on days 1 and 2, and rituximab 375 mg/m2 was given on day 1. BR was given for 4 cycles every 28 days. Patients were restaged 4-6 weeks after the last dose of BR. Patients were eligible for consolidation with 90YIT if they obtained at least a partial response after induction, had a platelet count greater than 100,000/mm3, a granulocyte count greater than 1,500/mm3, and bone marrow infiltration less than 25%. 90YIT was given 6-12 weeks after completion of the last cycle of BR. The primary endpoint is complete and unconfirmed complete response (CR/CRu) rate after sequential therapy with BR followed by 90YIT. Secondary endpoints are overall response rate after 4 cycles of BR, conversion rate from partial response (PR) after BR to CR/CRu after 90YIT, progression-free survival, and safety. The 1999 NHL Working Group Criteria was used to assess response. Results: From October 2010 to May 2014, forty-four patients were enrolled in this study (NCT01234766). 39 patients initiated treatment, and 5 were screen failures. Median age was 57 years [range 31-75]. The study enrolled FLIPI low (18%), intermediate (44%), and high (38%) risk patients; 33 of 39 (85%) were Grade 1-2 and 6 (15%) were Grade 3a. Twenty-two of 39 patients achieved CR/CRu (56%) and 16 of 39 patients had a PR (41%) for an overall response rate (ORR) of 97%. One patient had stable disease (SD). Four patients were not randomized to receive 90YIT: one in CR and one in PR were unable to receive 90YIT due to thrombocytopenia, one only achieved SD after BR, and one declined treatment. Thirty of 35 evaluable patients were in CR/CRu (86%), 4 remained in PR (11%) after 90YIT and one progressed during 90YIT, for an ORR of 97%. The number of patients in PR after BR who reached CR/CRu immediately after 90YIT were 10 of 16 (63%). Three (19%) additional patients converted to CR/CRu during follow-up, the latest occurring 16 months after 90YIT. After a median follow up of 30 months, 25 patients (71%) remain in CR/CRu, 10 patients (29%) have progressed/relapsed with a 24-month PFS of 80% (95% CI 63-90) [Figure]. The median PFS was not reached. Grade 3-4 hematologic toxicities during the 90YIT period included: neutropenia (34%), leukopenia (37%), thrombocytopenia (40%), lymphopenia (15%), and anemia (6%). There were no incidences of febrile neutropenia. One patient developed JC Virus/Progressive Multifocal Leukoencephalopathy, 13 months after receiving the last dose of rituximab and 90YIT on study. One patient developed chronic myeloid leukemia 11 months after, one patient developed acute myeloid leukemia 15 months after, and one patient developed uterine cancer 52 months after all study treatment. One patient died to progression of the lymphoma, 35 months after treatment. There have been no reported cases of myelodysplasia. Conclusions: In this 2.5 year report of patients that received BR followed by 90YIT, the CR/CRu rate of patients completing all study therapy is 71% and the 24-month PFS is 80%. There is a high rate of conversion in partial responders to CR/CRu (81%), some occurring more than one year after treatment with 90YIT. The durable PFS is comparable to what is reported in the FIT trial (Morschhauser et al. JCO 2013) and the phase II Spanish intergroup study (Canales et al. ASH 2013). BR followed by 90YIT is a well-tolerated regimen for follicular lymphoma with high response rates that is a safe and highly effective as first-line therapy. Long-term safety reflects the natural history of patients with indolent lymphomas. Figure Figure. Disclosures Lansigan: Pharmacyclics: Consultancy; Teva: Research Funding; Celgene: Consultancy; Spectrum: Consultancy, Research Funding.

scholarly journals Management of Post-Transplant Lymphoproliferative Disorders in the Real Life: The French Attitude Between 2010 and 2013

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4230-4230
Author(s):  
Inès Boussen ◽  
Caroline Algrin ◽  
Julien Rossignol ◽  
Eric Durot ◽  
Sarah Guenounou ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Overall Response Rate ◽  
Response Rate ◽  
Chop Chemotherapy ◽  
First Line ◽  
Advisory Committees ◽  
Overall Response ◽  
National Expert ◽  
Expert Network

Abstract Introduction Post-transplant lymphoproliferative disorders (PTLD) are a rare but severe complication occurring after organ transplantation as a result of immunosuppressive therapy (IST). Until recently, there was no consensus regarding best treatment practice. In 2006, a phase 2 trial using a monotherapy with rituximab showed an overall response rate of 44%, with a complete response (CR) rate of 28%. In 2012, the PTLD-1 international multicenter trial evaluating rituximab followed by CHOP chemotherapy proved an efficacy of 90% and an overall survival of 6.6 years in PTLD treatment. K-virogref is a French national expert network created in 2011 to structure and improve the management of viro-induced cancers, occurring in adult after transplantation, including PTLD. Within this network, an epidemiological observational study has been set up in September 2013. The aim of our study was to analyze the management of PTLD in France before the creation of the national database of K-virogref. Patients and methods We included solid organ or allogeneic stem cell recipients, aged 18 years and above, with a histologically proven PTLD, diagnosed between January 2010 and September 2013 in 19 French hematology departments. We collected from clinical charts data regarding transplant characteristics, PTLD presentation, first-line treatment and outcomes. Results The study population consisted of 94 patients, 67% were men and median age was 53 years (ranging 18 - 81 years). The majority of patients received kidney transplantation (54%), followed in almost equal proportion by heart (13%), liver (13%) and allogeneic stem cell transplantation (10%). Most of the time (80% of patients), PTLD occurred more than one year after organ transplantation with a median delay of 7.8 years. Histologically, mainly monomorphic PTLD were observed with 66% of diffuse large B cell lymphoma and PTLD was EBV associated in 54%. At the time of diagnosis, 80% were classified as stage IV according to Ann Arbor. The median follow-up time was 28.3 months (ranging 0.2 - 78 months). As far as treatment is concerned, modification of IST was performed in 68% of patients but response was rarely evaluable because a specific treatment was often started at the same time. Surprisingly, first line treatment consisted in rituximab alone or rituximab followed by CHOP chemotherapy in only 32% of the patients. Among these patients, the overall response rate was 81% with 55% of CR. Most patients (56%) received chemotherapy (n=11) or immunochemotherapy (n=46) without previous rituximab therapy. For these patients the overall response rate was 71% with a CR rate of 53%. At 1 and 3 years of follow-up, the relapse-free rates were 56% (95% confidence interval (CI) 46% - 68%) and 47% (95% CI 37% - 60%), respectively. Overall, 49% of patients died during follow-up of which 37% due to infectious complications and 32% due to PTLD progression. Conclusion This is one of the largest cohort study of PTLD in the literature, providing an overview of epidemiological features, treatments and outcomes of this rare disease. The lag between the management of PTLD and literature data emphasizes the usefulness of a national expert network such as K-virogref in order to generalize a less toxic and more powerful attitude. Disclosures Leblond: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria. Choquet:Celgene: Consultancy; Janssen: Consultancy.

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