Interferon-Alpha With Or Without Rituximab Achieves a High Response Rate and Durable Responses In Relapsed FL: 17 years’ Experience In a Single Centre

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5126-5126
Author(s):  
Sinziana Radesi-Sarghi ◽  
Flavie Arbion ◽  
Caroline Dartigeas ◽  
Martine Delain ◽  
Lotfi Benboubker ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Interferon Alpha ◽  
Response Rate ◽  
Progression Free Survival ◽  
High Response Rate ◽  
High Response ◽  
Single Centre ◽  
Time To Relapse

Abstract Background Maintenance interferon-alpha (IFNa) immunotherapy after induction chemotherapy prolongs progression-free survival (PFS) in untreated follicular lymphoma (FL). Little information is available about IFNa use in relapsed FL. Objectives To evaluate the benefit of IFNa as treatment for low-burden FL relapse. Methods In this single-centre retrospective study, we analysed all patients with molecular or clinical relapsed low- burden FL who received 3MIU IFNa three times a week alone (16 times) or in combination with 4-weekly rituximab (R) (11 times), without chemotherapy, according to the institution’s policy. All responses were evaluated according to the IWG 1999 criteria, except for molecular relapses which are described separately. Results 20 patients (13 men, 7 women), treated for a total of 27 times with IFNa were identified, with a median follow-up of 85 months. At diagnosis, 17 patients had advanced III-IV stage and 5 of them a high tumour burden, according to GELA criteria. 5 patients were treated for molecular IGH-BCL2 relapses. The FLIPI score was intermediate or high risk in 37% of patients. The median age of patients at the first IFNa +/- R treatment was 51 years (range: 30-65). Patients had previously received a median of three lines of treatment (range: 1-6) and 59% had received anthracycline-based chemotherapy. In the 22 situations with measurable disease, the overall response rate (OR) was 70%, with 59% complete responses (CR). For patients with only detectable molecular disease (n=5), IFNa was used alone for a median duration of 15 months (range: 12- 21 months), MRD becoming negative in 4 patients. The only factor significantly correlated with maximum response was low FLIPI score calculated at study entry (p=0.02). Median PFS was 56.9 months, (95% CI: 0.8-113). The R-IFNa and IFNa subgroup outcomes did not statistically differ in response or PFS. The FLIPI score calculated at initiation of IFNa treatment was predictive of time to relapse (P=0.014). The overall survival at 5 years was 95 % (95%CI: 91-99): 100%  in the  IFNa group and 91% (95%CI: 82-100) in the R-IFNa group. Reported toxicity was low. Conclusion Interferon alpha with or without rituximab achieve high response rates in relapsed low burden follicular lymphoma. These results compare favorably with previous reports of the efficacy of R alone, and of R with IFNa in relapse. Further research is required to explore the role of IFNa in the management of FL. Disclosures: Gyan: Roche: Research Funding.

Interferon alpha with or without rituximab achieves a high response rate and durable responses in relapsed FL: 17 years’ experience in a single centre

2013 ◽  
Vol 93 (1) ◽  
pp. 147-156 ◽  
Author(s):  
Sinziana Radesi-Sarghi ◽  
Flavie Arbion ◽  
Caroline Dartigeas ◽  
Martine Delain ◽  
Lotfi Benboubker ◽  
...  
Keyword(s):  
Interferon Alpha ◽  
Response Rate ◽  
High Response Rate ◽  
High Response ◽  
Single Centre

Clinical outcome of patients with follicular lymphoma receiving chemoimmunotherapy in the PRIMA study is not affected by FCGR3A and FCGR2A polymorphisms

Blood ◽  
2012 ◽  
Vol 120 (13) ◽  
pp. 2650-2657 ◽  
Author(s):  
Hervé Ghesquières ◽  
Guillaume Cartron ◽  
John Francis Seymour ◽  
Marie-Hélène Delfau-Larue ◽  
Fritz Offner ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Follicular Lymphoma ◽  
Response Rate ◽  
Single Agent ◽  
Progression Free Survival ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Free Survival ◽  
Rituximab Maintenance

Abstract In patients with follicular lymphoma treated with single-agent rituximab, single nucleotide polymorphisms in the FCGR3A gene are known to influence response and progression-free survival. The prognostic role of FCGR3A and FCGR2A polymorphisms in patients with follicular lymphoma treated with rituximab and chemotherapy combination remains controversial and has not been evaluated in the context of rituximab maintenance. FCGR3A and FCGR2A single nucleotide polymorphisms were evaluated in, respectively, 460 and 455 patients treated in the PRIMA study to investigate whether these were associated with response rate and patient outcome after rituximab chemotherapy induction and 2-year rituximab maintenance. In this representative patient cohort, complete and unconfirmed complete responses after rituximab chemotherapy were observed in 65%, 67%, 66% (P = .86) and 60%, 72%, 66% (P = .21) of FCGR3A VV, VF, FF and FCGR2A HH, HR, RR carriers, respectively. After 2 years of rituximab maintenance (or observation), response rates did not differ among the different genotypes. Progression-free survival measured from either treatment initiation or randomization to observation or maintenance was not influenced by these polymorphisms. These data indicate that FCGR3A and FCGR2A polymorphisms do not influence response rate and outcome when rituximab is combined with chemotherapy or used as maintenance treatment. The PRIMA study is registered at www.clinicaltrials.gov as NCT00140582.

A Follow-up Investigation with High Response Rate

1988 ◽  
Vol 16 (3) ◽  
pp. 137-137
Author(s):  
Henrik Toft Sørensen ◽  
Bo Christensen ◽  
Erling Kjærulff
Keyword(s):  
Response Rate ◽  
High Response Rate ◽  
High Response

Bortezomib, Thalidomide, and Dexamethasone as Induction Therapy for Patients with Symptomatic Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3605-3605 ◽  
Author(s):  
Jonathan L. Kaufman ◽  
Charise Gleason ◽  
Leonard Heffner ◽  
Sagar Lonial
Keyword(s):  
Induction Therapy ◽  
Progressive Disease ◽  
Response Rate ◽  
Progression Free Survival ◽  
High Response Rate ◽  
High Dose ◽  
High Dose Therapy ◽  
Free Survival ◽  
One Year

Abstract The optimal induction regimen for patients with symptomatic myeloma who are eligible for transplantation is currently unknown. While thalidomide and dexamethasone is an effective regimen, it only has a 60 to 65% response rate and few complete responses (CR). Bortezomib based inductions have demonstrated a high response rate and an improved CR as well. Recently the IFM reported the initial results of the randomized bortezomib plus dexamethasone versus VAD induction followed by transplant, which demonstrated that fewer patients treated with bortezomib required tandem transplants. Wang et al reported a high induction response rate with the combination of BTD for only 2 cycles given over a 28 day cycle. Here we report our experience with the combination of BTD as induction therapy. 38 patients with symptomatic myeloma were treated with BTD as induction therapy. Patients received standard dose and schedule bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11 with thalidomide at 100 mg/day, and 8 days of 40 mg dexamethasone every 21 days. The median age was 58 years (38–70) with 19 males. This was first line therapy for 29 patients, second line for 7 patients and 3rd line for 2. 12 patients had ISS stage 2 and 8 had ISS stage 3. The median β2M was 3.4 (1.66–41.89). Median creatinine was 1.1 (0.6–21.0). Nineteen patients had an IgG paraprotein, 6 an IgA, and 16 patients had light chain disease. The median number of cycles administered was 4 (2–8). Fifteen patients developed neuropathy of any grade. One patient developed grade 3 neuropathy. The overall response rate (CR, VGPR, plus PR) was 92%, with 58% of patients achieving a VGPR or better, and 21% of patients achieving an immunofixation negative CR. 1 patient had a minimal response and 2 patients had progressive disease (both patients presented with plasma cell leukemia). These two patients were treated with the combination of BTD with PACE chemotherapy. One of the two died from progressive disease and the other patient remains in complete remission after high dose therapy and autologous transplantation. 29 patients had consolidation therapy with high dose melphalan and autologous peripheral blood stem cell transplantation. Eight patients have collected stem cells without proceeding with immediate consolidation therapy. After a median follow up of 373 days, median progression free survival and overall survival have not been reached. One year overall survival is 97%. One year progression free survival is 87%. In conclusion, we report a very high response rate with a short course of bortezomib, thalidomide and dexamethasone with an acceptable toxicity profile. Follow up of patients in CR treated without high dose therapy and autologous transplant is in progress. Further studies of this active regimen are warranted.

Extended Follow-Up of Reduced Intensity Transplantation with an Alemtuzumab-Containing Regimen for Follicular Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1666-1666
Author(s):  
Kirsty Thomson ◽  
Emma Morris ◽  
Donald Milligan ◽  
Ann Hunter ◽  
Gordon Cook ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Curative Therapy ◽  
Starting Dose ◽  
Unrelated Donors ◽  
Time To Relapse ◽  
Reduced Intensity

Abstract Allogeneic transplant with reduced intensity conditioning (RIC) is currently being investigated as potential curative therapy for patients with lymphoma. We report 64 consecutive patients with follicular lymphoma (FL) transplanted at 9 centres with a RIC regimen containing fludarabine 150mg/m2, melphalan 140mg/m2 and alemtuzumab (20–100mg). Cyclosporin A was given at 3mg/kg. Donors were HLA-matched siblings in 34 (53%), and unrelated in 30 (47%), of whom 9 (14%) were HLA-mismatched at up to 2/10 loci. Median age was 44 yrs (26–65), median lines of previous therapy was 3 (1–8) and 17 (27%) had failed a prior autograft. Fifty-five patients (86%) had chemosensitive disease pre-RIC (complete remission 11, partial remission 44), 8 (12%) were chemorefractory and 1 had untreated relapse. Median follow-up was 39 months (1–98). Non-relapse mortality (NRM) at 5 yrs was 12%, with 9% at 5 yrs for sibling donors and 15% for unrelated (p=0.41). There was no significant impact of prior autograft on NRM. Acute graft-versus-host disease (GVHD) grade II occurred in 11 (17%) with no grade III-IV, and extensive chronic GVHD occurred in 9 (16%). Relapse rate (RR) was 18% at 1 year and 32% at 5 years. Those who had failed a prior autograft had an increased RR (53% at 5 yrs) compared to those with no prior autograft (22% at 5 yrs; p=0.01). Median time to relapse from RIC was 8 months (1–43) with 15/17 events occurring within the 1st 2 years. Donor lymphocyte infusions (DLI) were given to 13 patients, at a starting dose of 1–10×106 CD3+/kg. Nine patients remitted, of whom 6 had no GVHD and 7 had received prior rituximab. Median follow-up from last DLI dose was 34 months (3–72). Overall survival (OS) for the whole cohort was 80% at 1 yr and 76% at 5 yrs. On univariate analysis, those with sibling donors had significantly improved OS (88% at 5 yrs), compared to unrelated donors (61% at 5 yrs; p=0.016), as did those with chemosensitive disease pre-RIC (80% at 5 yrs) compared to chemorefractory disease (50% at 5 yrs; p=0.028), and those who had not undergone a prior autograft (86% at 5 yrs) compared to those who had (47% at 5 yrs; p=0.001). Similarly, current progression-free survival (cPFS) for the whole cohort was 79% at 1 yr and 77% at 5 yrs, with significantly superior outcome in those with sibling donors (88% at 5 yrs) compared to unrelated donors (63% at 5 yrs; p=0.018), those with chemosensitive disease (81% at 5 yrs) compared to those with chemorefractory disease (50% at 5 yrs; p=0.0198), and those who had not failed a prior autograft (86% at 5 yrs) compared to those who had (50% at 5 yrs; p=0.001). No factor remained significant for OS or cPFS on multivariate analysis. In conclusion, RIC for FL using an alemtuzumab-containing regimen can be undertaken with relatively low rates of significant acute and chronic GVHD, and low NRM for both HLA-matched and mismatched related and unrelated donors. Responses to DLI occur, often in the absence of clinical GVHD, and appear durable so far, although further follow-up is required.

scholarly journals High Response Rate to Antidepressants in the Management of Paroxysmal Hypertension (Pseudopheochromocytoma)

2021 ◽  
Author(s):  
Samuel J. Mann ◽  
Kaushal V. Solanki
Keyword(s):  
Response Rate ◽  
Case Series ◽  
Preventive Treatment ◽  
High Response Rate ◽  
High Response ◽  
Response To Treatment ◽  
Paroxysmal Hypertension ◽  
Treatment Data ◽  
Lost To Follow Up

There is no widely recognized preventive treatment for patients with paroxysmal hypertension (“pseudopheochromocytoma”) who suffer recurrent and often severe paroxysmal elevation of blood pressure, repeated emergency room visits and hospitalizations. In this case series we assessed the effectiveness of treatment with an antidepressant in preventing recurrent paroxysms. A secondary exploratory objective was to examine the psychological profile of patients and its relationship to response to treatment. The charts of 52 patients who reported having experienced at least 3 symptomatic episodes were selected; and and for whom treatment data were included. Treatment with an antidepressant was offered to, and follow-up data were available in 37..Two patients refused treatment, 6 were unable to tolerate an effective dose, 3 were lost to follow-up, and 1 was non-compliant with the medication. Of the remaining 25 evaluable patients, 92% (23/25) responded, with 80% (21/25) achieving complete and persisting cessation of paroxysms, and 8% (2/25), a reduction in frequency. Importantly, an antidepressant was effective in nearly all patients who reported that they were not suffering from anxiety or depression. The data were insufficient to determine superiority of any one antidepressant versus another. We conclude that treatment with an antidepressant is effective in preventing hypertensive paroxysms in a high proportion of patients with paroxysmal hypertension. Given the absence of any other pharmacologic intervention capable of preventing recurrent paroxysms, the similarly high response rate observed in previous reports, and the relatively safe profile of antidepressant agents, the findings support more widespread use of an antidepressant in patients with this disorder to prevent years of continued hypertensive paroxysms and their consequences.

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.

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