Meta Analysis: Rituximab as Maintenance Therapy for Patients with Follicular Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3408-3408
Author(s):  
Liat Vidal ◽  
Anat Gafter-Gvili ◽  
Martin Dreyling ◽  
Michele Ghielmini ◽  
Shu Fang Hsu-Schmitz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Induction Therapy ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Separate Analysis ◽  
Newly Diagnosed ◽  
Single Infusion ◽  
Number Of Patients

Abstract Background: Rituximab in combination with chemotherapy improves overall survival (OS) compared to chemotherapy alone when used for induction therapy, for patients with newly diagnosed and relapsed indolent lymphoma. Randomized controlled trials (RCTs) have demonstrated that maintenance treatment with rituximab (MR) prolongs progression free survival but evidence of effect on OS is lacking. Objectives: to evaluate the effects of MR on OS in patients with follicular lymphoma (FL). Methods: Systematic review and meta-analysis of RCTs that assessed MR for patients with B cell FL. Electronic databases of medical journals and ongoing trials were searched. Relative risks (RR) for dichotomous outcomes with 95% confidence intervals (CI) were pooled using Mantel-Haenszel method. Treatment effect on OS was estimated as hazard ratios (HRs) using methods described by Parmar et al. (Stat Med1998;17:2815–34) Results: 266 titles and abstracts were screened. Five trials fulfilled inclusion criteria (table). 1053 adult patients were randomized between the years 1998–2004. The median follow up ranged between 26 to 41 months. The minimal requirement for inclusion was either a stable disease after induction (3 trials) or partial remission (2 trials). Overall survival: Four trials (895 patients) were included in analysis of OS. The Hainsworth trial (JCO2006; 23: 1088–1095) was omitted for analysis of OS due to design issues (MR versus retreatment at progression). Patients treated with MR had a significantly better OS compared to observation (HR 0.53, 95% CI 0.39, 0.73). Adverse events: Patients treated with MR had more infectious related adverse effects compared to observation (RR 1.99, 95% CI 1.21, 3.27). Conclusions: MR improves OS compared to observation in patients with refractory/relapsed FL who responded to induction therapy. Pooled HR of OS with MR treatment versus observation for patients with FL. n number of events; N number of patients evaluated. Rituximab as maintenance therapy for patients with follicular lymphoma Overall survival Rituximab as maintenance therapy for patients with follicular lymphoma Overall survival Description of included trials Trial ID No. randomized patients Type of lymphoma Induction therapy Rituximab maintenance protocol *Separate analysis was possible for patients with FL. Y years, SLL small lymphocytic lymphoma, MCL mantle cell lymphoma, CVP cyclophosphamide, vincristine, prednisone, FC fludarabine, cyclophosphamide, FCM fludarabine, cyclophosphamide, mitoxantrone, CHOP cyclophosphamide, doxorubicin, vincristine, prednisone Hainsworth 2005 90 Previously treated FL, SLL Rituximab Weekly for 4 weeks every 6 months for 2y Hochster 2005 304 Untreated FL, SLL* CVP Weekly for 4 weeks every 6 months for 2y Hochster 2007 69 Untreated FL, SLL FC Same as above Forstpointner 2006 195 Relapsed FL, MCL* FCM+/− rituximab Weekly for 4 weeks, at 3 and 9 months Ghielmini 2004 151 Newly diagnosed and relapsed FL Rituximab A single infusion every 2 months for four doses van Oers 2006 334 Relapsed FL CHOP+/− rituximab A single infusion every 3 months for 2y

Maintenance Therapy With Bortezomib and Dexamethasone for Transplant-ineligible Patients With Multiple Myeloma

2021 ◽  
Vol 1 (2) ◽  
pp. 35-42
Author(s):  
YURIKA NOGUCHI ◽  
NORIYOSHI IRIYAMA ◽  
HIROMICHI TAKAHASHI ◽  
YOSHIHITO UCHINO ◽  
MASARU NAKAGAWA ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Maintenance Therapy ◽  
Induction Therapy ◽  
Survival Rates ◽  
Patient Characteristics ◽  
Newly Diagnosed ◽  
Estimated Glomerular Filtration Rates ◽  
Overall Survival Rates ◽  
Maintenance Group

Background/Aim: Here, we investigated whether bortezomib as a maintenance therapy affected outcomes in transplant-ineligible patients with multiple myeloma (MM). Patients and Methods: Following induction therapy with bortezomib, maintenance therapy with bortezomib (1.3 mg/m2) and dexamethasone (20 mg) was administered once or twice every 4 weeks until disease progression. The endpoints of this study were time to next treatment and overall survival. Results: Seventy-six newly diagnosed, transplant-ineligible patients were treated with a bortezomib-based regimen; 28 discontinued induction therapy, 27 did not receive maintenance therapy after induction therapy (the non-maintenance group), and 21 did (the maintenance group). In the three groups, the median times to the next required treatment were 3, 14, and 37 months, respectively. The 3-year overall survival rates were 55%, 69%, and 85%, respectively. There were no significant differences in patient characteristics between the non-maintenance and maintenance groups, except for poorer estimated glomerular filtration rates in the maintenance group. Conclusion: Bortezomib maintenance therapy may be a useful option for transplant-ineligible patients with MM.

scholarly journals Impact of post-ASCT maintenance therapy on outcomes in patients with newly diagnosed multiple myeloma in Connect MM

2018 ◽  
Vol 2 (13) ◽  
pp. 1608-1615 ◽  
Author(s):  
Sundar Jagannath ◽  
Rafat Abonour ◽  
Brian G. M. Durie ◽  
Mohit Narang ◽  
Howard R. Terebelo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Maintenance Therapy ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Second Primary ◽  
Newly Diagnosed ◽  
Serious Adverse Events ◽  
Using Data

Abstract Autologous stem cell transplantation (ASCT) followed by lenalidomide maintenance therapy is the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). Clinical trials show progression-free survival (PFS) benefits, with some studies (Cancer and Leukemia Group [CALGB] trial and meta-analysis) also showing overall survival (OS) benefits, but applicability to real-world clinical settings is unclear. Using data from Connect MM, the largest US-based observational registry of NDMM patients, we analyzed effects of maintenance therapy on long-term outcomes in 1450 treated patients enrolled from 2009 to 2011. Patients who received induction therapy and ASCT (n = 432) were analyzed from 100 days post-ASCT (data cut 7 January 2016): 267 received maintenance (80% lenalidomide-based [of whom 88% received lenalidomide monotherapy]); 165 did not. Lenalidomide maintenance improved median PFS and 3-year PFS rate vs no maintenance (50.3 vs 30.8 months [hazard ratio (HR), 0.62; 95% confidence interval (CI), 0.46-0.82; P < .001] and 56% vs 42%, respectively). Improvements in median OS and 3-year OS rate were associated with lenalidomide maintenance vs no maintenance (not reached in either group [HR, 0.54; 95% CI, 0.36-0.83; P = .005] and 85% vs 70%, respectively). Five hematologic serious adverse events were reported with lenalidomide maintenance (pancytopenia [n = 2], febrile neutropenia, anemia, and thrombocytopenia [n = 1 each]) and 1 with no maintenance (thrombocytopenia). Second primary malignancies occurred at rates of 1.38 and 2.19 events per patient-year in lenalidomide maintenance and no maintenance groups, respectively. Survival benefits associated with lenalidomide maintenance previously demonstrated in clinical trials were observed in this community-based Connect MM Registry.

Maintenance Therapy with Rituximab for Follicular Lymphoma Is Cost-Effective – A Canadian Perspective.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 343-343 ◽  
Author(s):  
Bridget Maturi ◽  
Joseph R. Mikhael ◽  
William C.N. Dunlop ◽  
Dominic T. Tilden ◽  
Lisa Wong
Keyword(s):  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Induction Therapy ◽  
Drug Acquisition ◽  
Progression Free Survival ◽  
Cost Effective ◽  
Health State ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
Canadian Perspective

Abstract Background: Rituximab maintenance therapy has been shown to significantly improve overall survival (OS) (p<0.0111) and progression free survival (PFS) (p<0.0001) compared to observation alone in patients with relapsed/refractory follicular lymphoma (van Oers MHJ et al, et al. Blood. 2006 [Epub ahead of print]).The objective of this analysis was to estimate the cost-effectiveness, from a Canadian perspective, of rituximab maintenance therapy versus observation alone (OA) in relapsed/refractory follicular lymphoma patients following response to induction therapy with or without rituximab, based on data from the European Organisation for Research and Treatment of Cancer (EORTC) 20981 study (Clinical Study Report 1016350). Methods: The impact of rituximab maintenance therapy (375 mg/m2 every 3 months until progression or for 2 years) compared with OA was evaluated using a lifetime, health-state transition model. All patients entered the model following response to chemotherapy +/− rituximab as induction therapy (progression-free health state [PFHS]). The model simulates the movement of patients from PFHS to either progressed health state (PHS) or death based on the data from the study. PFS and OS following rituximab maintenance were extrapolated from 2-year Kaplan-Meier curves from the study data using a Weibull distribution. In the base case model, the PFS and OS benefits of rituximab maintenance therapy were conservatively assumed to last only 5 years. Quality of life utility values for the health states in the model were derived from a study of 165 patients using the EQ-5D questionnaire. Direct annual medical costs including drug acquisition, administration and preparation were estimated from published sources. All costs are reported in 2005 Canadian dollars (CAD). Costs and outcomes were discounted at a rate of 5%. In order to address uncertainty in point estimates, one-way sensitivity analyses were also performed. Results: From the model, the estimated life-time incremental PFS for rituximab maintenance therapy was a 1.4 year increase over OA (3.1 vs 1.7 years). OS of rituximab maintenance patients was 0.9 years longer than in OA patients (5.6 vs 4.7 years). Total cost for rituximab maintenance therapy was estimated to be CAD34,748, with the majority of costs related to drug acquisition (CAD18,652). Rituximab maintenance resulted in a gain of 0.8 Quality Adjusted Life Years (QALYs) (4.0 vs [OA] 3.2 QALYs) at an incremental cost of CAD17,136. The incremental cost effectiveness ratio (ICER) of rituximab maintenance vs OA is, therefore, estimated to be CAD20,428 per QALY gained. The ICER of rituximab maintenance was sensitive to the duration of treatment benefit and frequency of subsequent treatment. Conclusions: In patients responding to induction therapy, rituximab maintenance therapy improves overall survival and progression-free survival compared with observation alone. This pharmacoeconomic model demonstrates that maintenance therapy with rituximab is a cost-effective approach for the management of patients with follicular lymphoma.

Analysis of Outcome after Autologous Stem Transplantation in Patients with Newly Diagnosed Myeloma: Comparison of Different Induction Regimens.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3079-3079 ◽  
Author(s):  
Shaji Kumar ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
Suzanne R. Hayman ◽  
S. Vincent Rajkumar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Induction Therapy ◽  
Stem Cell Transplant ◽  
Single Agent ◽  
Progression Free Survival ◽  
Initial Therapy ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Free Survival

Abstract Background: Autologous stem cell transplantation (SCT) improves survival in patients (pts) with multiple myeloma (MM). We have previously demonstrated that the degree of response at transplant does not impact on the outcome of transplant. However, newer induction regimens such as thalidomide and dexamethasone (Thal-Dex) result in higher response rates compared to previously used regimens such as single agent dexamethasone or vincristine, doxorubicin, and dexamethasone (VAD). We examined the outcome of SCT following three different induction therapies for newly diagnosed MM, namely VAD, single agent Dex, and Thal-Dex. Patients and Methods: 340 patients with MM who received their SCT within 12 mos of diagnosis (median 5.8, range 3–12) were studied. Patients receiving more than one induction therapy as well as those in whom thalidomide was added to dexamethasone for lack of response were excluded from the analysis. There were 105 pts in the VAD group, 140 in the Dex group and 95 in the Thal-Dex group. Responses were defined using standard criteria. Results: The study cohort consisted of 209 males (59%), with a median age of 57 years (range 30–76) at transplant. Baseline characteristics were similar in the 3 groups, except for lower age in the VAD group (median 55.8) compared to Dex (59.6) and Thal Dex (57.4) and shorter time to transplant in the Dex group (5.4 m) compared to VAD (6.4) and Thal Dex (5.9). Markers of disease activity pre-transplant, including B2M and marrow plasma cell percentage were higher in the Dex group compared to either VAD or Thal Dex. The proportion of patients with any response to induction therapy was lower in the Dex group compared to the other two. All pts in the Dex and the Thal-Dex groups received melphalan only conditioning compared to 70% in the VAD group, the rest receiving Melphalan/TBI. An objective response was achieved after SCT in 96%, 97%, and 98% of pts in the VAD, Dex and Thal-Dex groups respectively (P=0.8). A complete response to SCT was seen in 49% of patients in VAD group, 45% among those in the Dex group and 38% among those in the Thal Dex group (P=0.38). There was no difference in the median progression free survival after transplant (P=0.21) or overall survival from diagnosis (P=.34) between the three groups. The proportion free from progression at 2 years post transplant was 54%, 55% and 46% for Dex, VAD and Thal-Dex respectively. The proportion surviving at 4 years from diagnosis was 64%, 65.4% and 72% respectively for the three groups. Conclusion: We did not observe any difference in the response rates including complete responses to SCT in the three groups with nearly all pts in each group achieving a response. The progression free survival and overall survival appear to be comparable between the three groups. The results from initial therapy cannot be compared between the three regimens since the study population is restricted to patients reaching stem cell transplant. Within the limits of the study, there does not appear to be any long term impact of the initial therapy for the patients going onto an early stem cell transplant. Figure Figure

A Phase IIIb Study of Rituximab Maintenance Therapy in Patients with Follicular Non-Hodgkin’s Lymphoma Who Have Responded to Induction Therapy - MAXIMA-Protocol.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4706-4706 ◽  
Author(s):  
Manfred Hensel ◽  
Mathias Witzens-Harig ◽  
Peter Dreger ◽  
Anthony D. Ho ◽  
Daniel Thurley ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Induction Therapy ◽  
Randomized Trials ◽  
Phase Iii ◽  
First Line ◽  
Free Survival ◽  
Rituximab Maintenance

Abstract Five randomized trials (four Phase III and one phase II) have confirmed that rituximab maintenance therapy provides clinical meaningful improvements in terms of Progression Free Survival, Event Free Survival and response duration for patients. Two studies have also found an overall survival advantage for rituximab maintenance therapy (Hoechster et al. 2005, van Oers et al. 2005) and a third study could demonstrate a strong trend towards overall survival advantage (Dreyling et al. 2006). A Cochrane meta-analysis of several randomised Phase III trials (Schulz et al. 2005) demonstrated that rituximab plus-chemotherapy for first-line treatment of Follicular Lymphoma is superior to chemotherapy alone and significantly prolongs overall survival. To further broaden the available basis for maintenance treatment in the first-line and relapsed setting, the MAXIMA (MAintenance rituXImab in Follicular LymphoMA) trial has been started in August 2006 and will last 5 years. Patients with first line or relapsed/refractory advanced Follicular Lymphoma are included in this trial. In total 500 patients are planned for this international trial running in 23 countries. Patients who achieve a Complete Remission, Complete Remission unconfirmed or Partial Remission after rituximab containing induction therapy (rituximab with or without chemotherapy) are eligible to enter the study to receive rituximab maintenance therapy administered at the standard dose of 375 mg/m2 every 2 months for 2 years. This regimen is also investigated in the ongoing PRIMA study, and also in an ongoing SAKK study which investigates the benefit of rituximab maintenance therapy for up to five years. The previous five randomized trials did not detect significant safety issues for rituximab maintenance therapy. The main objective of the MAXIMA trial is to confirm this safety data in a wider patient population. Secondary objectives of the study include standard time dependent parameters (PFS, EF, OS). In addition, the effect of rituximab maintenance therapy on improving response quality (PR =&gt;CR) after induction therapy will be evaluated.

Bortezomib-Based Therapy without Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma Patients with t(4;14): A Canadian National Trial,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3982-3982
Author(s):  
Donna E. Reece ◽  
Giovanni Piza Rodriguez ◽  
David Szwajcer ◽  
Leonard A Minuk ◽  
Mariela Pantoja ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stem Cell ◽  
Maintenance Therapy ◽  
Disease Progression ◽  
Induction Therapy ◽  
Research Funding ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Newly Diagnosed

Abstract Abstract 3982 Newly diagnosed multiple myeloma (MM) patients (pts) with t(4;14) identified by FISH who undergo a single ASCT after older induction regimens have a median progression-free survival (PFS) of only 8–9 months (mos) and median overall survival (OS) of 18 mos (Chang H, et al. Bone Marrow Transplan t 2005; 36: 793; Gertz M, et al. Blood 2005; 106: 2837). Given the efficacy of bortezomib in t(4;14) disease, we designed a phase II study based on this agent in which ASCT was not performed as part of first-line therapy. Pts received induction therapy with four 21-day cycles of pegylated liposomal doxorubicin 30 mg/m2on day 4, bortezomib 1.3 mg/m2on days 1, 4, 8, 11 and dexamethasone 40 mg on days 1–4, 8–11, 15–18 of cycle 1 and on days 1–4 and 11–14 of cycles 2–4 (DBD), followed by post-induction therapy with eight 28-day cycles of oral cyclophosphamide 300 mg/m2on days 1, 8, 15, 22, bortezomib 1.5 mg/m2 on days 1,8,15 and prednisone 100 mg q 2 days (CyBor-P). Maintenance therapy with dexamethasone 40 mg/weekly was then administered until disease progression. Although elective stem cell collection was recommended after induction therapy, routine ASCT was not performed in the absence of disease progression. Between February 2008-May 2011, 383 newly diagnosed MM pts were screened for t(4;14) in 8 Canadian centers, and 43 (11.2%) were found to be positive by FISH. Five did not meet the CRAB criteria for symptomatic MM, 7 were ineligible, 3 declined participation and 28 were entered onto study. One of these was later determined to have a variant abnormality of chromosome 4, but not t(4;14), and underwent ASCT after induction therapy; this pt is included in the safety analysis only. The median age was 60 years (range 42–69) and 63% were male. The median percent of nuclei positive for t(4;14) by FISH in the initial bone marrow (unpurified) was 26% (range 2–62), serum β2-microglobulin 239 nmol/L (range 43–1695) and albumin 36 g/L (range 28–48); ten pts had ISS stage 1,10 had stage 2 and 7 had stage 3 MM. Immunoglobulin subtype included IgGκ in 7, IgAκ in 6, IgAλ in 6, IgGλ in 5 and IgMλ in 1. Using modified uniform criteria, the best response in 23 evaluable pts includes: sCR in 6 (26%), CR in 4 (17%), VGPR in 9 (39%), PR in 2 (9%) and SD in 2 (9%). Median F/U is 13.5 mos (range 1.2–35); 6 have progressed at median of 3 mos on study (range 1–11). Four pts have died (due to progression in 3 and complex medical problems/consent withdrawal in 1 in VGPR). SAEs were reported in 7 pts; only 6 pts (21%) developed grade 2 peripheral neuropathy, which necessitated dose reductions of bortezomib in 4. The actuarial 2-yr PFS is 47.7% (95%CI 25.9–87.9%), median PFS is 23. 2 months and 2-yr OS is 76.8% (95%CI 58.3–100%); the median OS has not yet been reached. We conclude: 1) the incidence of t(4;14) by FISH in newly-diagnosed MM pts is 11.2%; which appears to be lower than the 15% anticipated 2) 11.6% of these are asymptomatic; 3) this bortezomib-based regimen is well-tolerated; 4) the overall response rate (sCR + CR + VGPR + PR) is 91% with 82% achieving ≥ VGPR and 43% ≥ CR; 5) the PFS and OS with this approach compare favorably with those seen with older studies of single or double ASCT, and even with some recently reported trials using more modern induction regimens before ASCT, in pts with t(4;14); and 6) the use of more effective maintenance therapy, including agents targeting the aberrations associated with t(4;14), would be of interest in future trials. Disclosures: Reece: Millennium: Research Funding; Otsuka: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Johnson&Johnson: Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Bristol, Meyers, Squibb: Honoraria, Research Funding; Amgen: Honoraria. Off Label Use: Bortezomib regimens other than VMP (boretzomib, melphalan and prednisone)for initial therapy of myeloma. Piza Rodriguez:Celgene: Unrestricted educational grant; Otsuka: Honoraria. Belch:Ortho/Janssen: Honoraria; Celgene: Honoraria. White:Celgene: Consultancy, Honoraria, Research Funding; Ortho/Janssen: Honoraria, Research Funding. Chen:Celgene: Research Funding. Kukreti:Celgene: Honoraria.

Sequential RCHOP, Radioimmunotherapy and Rituximab Maintenance Improves Early Outcomes in Advanced Stage Follicular Lymphoma: 5 Year Outcomes from SWOG 0801

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 614-614
Author(s):  
Paul M. Barr ◽  
Hongli Li ◽  
Richard Burack ◽  
Michael LeBlanc ◽  
Sonali M. Smith ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Research Funding ◽  
Progression Free Survival ◽  
Advanced Stage ◽  
Secondary Malignancies ◽  
Free Survival ◽  
Grade 3

Abstract Background: Despite an abundance of effective therapeutic options, advanced stage follicular lymphoma (FL) remains incurable. Further, prospective trials consistently demonstrate that 20% of patients relapse within 2 years and ultimately have an inferior survival (Casulo 2015). Maintenace rituximab following chemoimmunotherapy induction is able to delay disease progression but has not demonstrated a benefit in overall survival (Salles 2011). Additionally, radioimmunotherapy (RIT) is one of the most effective single agent options in FL but is not commonly utilized as part of upfront treatment. As such, the role of both remains unclear. Based on results demonstrated with RIT consolidation in SWOG 0016 and the efficacy of rituximab maintenance, SWOG 0801 was designed as a phase 2 single arm trial, conducted to evaluate the utility of consolidative RIT and sequential maintenance rituximab following chemoimmunotherapy induction. Methods: Eligible patients (pts) with treatment naïve stage III/IV or bulky stage II FL received RCHOP for 6 cycles (without rituximab for the last 2 cycles) followed by iodine-131 tositumomab and subsequent rituximab administered every 3 months for up to 4 years. The primary endpoint was progression-free survival (PFS) at 3 years. Secondary endpoints included 5-year overall survival (OS), overall response rate (ORR), and safety. Results: Of 87 pts registered to this study, 85 were deemed eligible following central pathologic review. One additional patient withdrew consent and received no treatment on protocol. Of the 84 evaluable patients, the median age was 52 years (range 29 - 80) ) and 18%, 40%, and 42%had low, intermediate and high risk FLIPI scores, respectively. Seventy-three pts completed RCHOP and I-131 tositumomab. Grade ≥3 AEs occurring ≥5% of pts included neutropenia (57%), leukopenia (40%), thrombocytopenia (20%), febrile neutropenia (17%), fatigue (10%), neuropathy (8%), anemia (7%) and hyperglycemia (5%). Reasons for discontinuation included refusal of tositumumab (6 pts), prolonged myelosuppression (2 pts), ascites (1pt), inability to provide tositumumab (1 pt), and an unrelated lower extremity wound (1 pt). Following induction and RIT, 59 complete responses and 23 partial responses were observed, for a ORR of 99% (95% CI: 93.5%, 99.9%) Sixty nine eligible patients registered to maintenance therapy with 42 completing the 4 year treatment plan. The only grade ≥3 AE that occurred in ≥5% of pts was leukopenia (5%). Twenty-seven pts discontinued maintenance therapy, including 11 in the first 2 years and 16 in the last 2 years, due to the following reasons: infection (8 pts), patient preference (8 pts), deaths (2 pts), treatment delay (2 pts), secondary solid tumors (2 pts), bowel perforation (1 pt), joint pain (1 pt), hepatic transaminase elevation (1 pt), insurance refusal (1 pt), and dose error (1 pt). Four additional secondary malignancies were reported following completion of therapy including solid tumors (3 pts) and AML (1 pt). To date, 9 deaths have occurred due to secondary malignancies (3 pts), unknown etiology (3 pts), cardiac arrest (2 pts) and non-alcoholic cirrhosis (1 pt). After median follow-up of 5.6 years (range 3-7 years), 17 events have occurred including 9 pts experiencing progressive FL resulting in a progression free survival of 90% (95% CI: 81.9%, 95.1%) at 3 years and 84%(95% CI: 74.5%, 90.6%) at 5 years (Figure). Three-year overall survival is 96% (95% CI: 89.3%, 98.8%) and 5-year overall survival is 94% (95% CI: 86.2%, 97.5%). Conclusions: SWOG 0801 demonstrates near universal responses following chemoimmunotherapy and RIT. This sequential therapeutic strategy appears to improve early outcomes as 94% of pts are without disease progression at 2 years, consistent with the best results ever demonstrated for FL in the National Clinical Trials Network. However, the majority of discontinuations occurred during maintenance suggesting that rituximab over a 4-year span is not feasible for many patients due to cumulative toxicity. Future studies investigating precision strategies in high-risk FL may consider an aggressive chemoimmunotherapy induction and RIT consolidation platform to overcome early FL progression given these promising outcomes. Support: NIH/NCI grants CA180888, CA180819, and in part by GlaxoSmithKline. Figure. Progression-Free Survival and Overall Survival Figure. Progression-Free Survival and Overall Survival Disclosures Barr: Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; AbbVie: Consultancy. Smith:Amgen: Other: Educational lecture to sales force; Juno: Consultancy; Pharmacyclics: Consultancy; AbbVie: Consultancy; Portola: Consultancy; Celgene: Consultancy; Gilead: Consultancy; Genentech: Consultancy, Other: on a DSMB for two trials ; TGTX: Consultancy. Gopal:Janssen: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Spectrum: Consultancy. Persky:Merck: Research Funding; Gilead: Speakers Bureau. Press:Roche / Genentech: Consultancy, Research Funding. Fisher:Gilead: Consultancy; Seattle Genetics: Consultancy; Johnson and Johnson: Consultancy. Friedberg:Bayer: Other: Data Safety Monitoring Committee.

scholarly journals The impact of extended adjuvant temozolomide in newly diagnosed glioblastoma multiforme: a meta-analysis and systematic review

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Ehsan Alimohammadi ◽  
Seyed Reza Bagheri ◽  
Shahram Taheri ◽  
Maliheh Dayani ◽  
Alireza Abdi
Keyword(s):  
Overall Survival ◽  
Glioblastoma Multiforme ◽  
Maintenance Therapy ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Control Group ◽  
Case Group ◽  
Free Survival ◽  
Upper Limits ◽  
The Impact

Surgical resection followed by concurrent radiation therapy and temozolomide (TMZ) chemotherapy is the current standard treatment for glioblastoma multiforme (GBM). The present metaanalysis investigated the impact of prolonged TMZ maintenance therapy (more than 6 cycles) in comparison with standard TMZ maintenance therapy (exactly six cycles) on overall survival (OS) and progression-free survival (PFS) of patients with GBM. A meta-analysis of the literature was conducted using Medline, PubMed, EMBASE and the Cochrane Library in accordance with PRISMA guidelines. Seven articles involving 1018 patients were included. The overall survival was higher in the case group (>6 cycles TMZ) compared to the control group (6 cycles TMZ) (Z=2.375, P=0.018). The lower and upper limits were between 1.002-10.467 months. The case group had higher progression-free survival compared with the control group (Z=3.84; P<0.001). The lower and upper limits were between 2.559-7.894 months. Evidence from this meta-analysis suggests that prolonged TMZ therapy compared to the standard 6-cycle TMZ therapy was associated with higher survival in patients with glioblastoma.

scholarly journals Lenalidomide Compared to Ixazomib Maintenance in Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3776-3776
Author(s):  
Eunice Lai ◽  
Yu Yang Soon ◽  
Ainsley Ryan Yan Bin Lee ◽  
Shi Yin Wong ◽  
Cinnie Yentia Soekojo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Research Funding ◽  
Meta Analysis ◽  
Proteasome Inhibitors ◽  
Progression Free Survival ◽  
Risk Of Bias ◽  
Newly Diagnosed ◽  
Maintenance Strategies

Abstract Background Maintenance therapy is considered a standard of care in transplant eligible (TE) and non transplant eligible (NTE) patients with newly diagnosed multiple myeloma (NDMM). While immunomodulators (IMID) and proteasome inhibitors (PI) have been proposed as maintenance therapy options, there are no randomised trials (RCTs) directly comparing these agents in the maintenance setting. The IMID lenalidomide (Len) and the PI ixazomib (Ixa) have been compared against placebo as maintenance strategies in NDMM. We present a network meta-analysis (NMA) of RCTs comparing the efficacy and safety of Len and Ixa maintenance therapies in NDMM. Methods We searched various biomedical databases for eligible studies evaluating Len or Ixa against placebo/ observation as maintenance therapy in patients with NDMM from date of inception through November 2020. The primary outcome was progression-free survival (PFS). Secondary outcomes include overall survival (OS) and adverse events (AE). The Cochrane risk of bias tool version 2.0 was used to assess trial quality. A Bayesian NMA model was used to assess the relative effects of competing treatments on PFS and OS outcomes. Adverse events were assessed using the synthesis without meta-analysis (SWIM) approach due to variability in the toxicity scoring criteria. The GRADE approach was used to rate the certainty of the evidence. This study is registered with PROSPERO, CRD42021226157. Results We identified eight studies including 3229 transplant eligible (TE) and 1689 non transplant eligible (NTE) patients. All studies were judged to have low risk of bias. Len but not Ixa was associated with statistically significant improvement in PFS when compared to placebo in TE (Len: Hazard Ratio (HR) 0.46, 95% Credible Interval (CrI) 0.35-0.56, high certainty; Ixa: HR 0.72, 95% CrI 0.46-1.13, moderate certainty) and NTE (Len: HR 0.46, 95% CrI 0.29-0.75, high certainty; Ixa: HR 0.69, 95% CrI 0.43-1.18, moderate certainty). Bayesian modelling demonstrated a 97% and 93% probability that Len resulted in superior PFS compared to Ixa in TE and NTE patients respectively. Both Len and Ixa were not associated with statistically significant improvement in OS compared to placebo in TE and NTE patients. There was no significant effect modification on the effect of Len vs placebo and Ixa vs placebo by cytogenetics status, use of proteasome inhibitors for induction or duration of maintenance therapies for PFS and/or OS outcomes. Len were judged to have a higher incidence of second malignancies and grade 3 or 4 neutropenia than Ixa while Ixa was judged to have a higher incidence of thrombocytopenia than Len. Conclusions Maintenance therapy with Len may provide a larger PFS benefit than Ixa regardless of type of induction therapy and cytogenetic risk in patients with NDDM. The differing toxicity profile of these agents is also an important consideration for treatment decisions. RCTs directly comparing these maintenance strategies are warranted. Figure 1 Figure 1. Disclosures Ooi: Jansen: Honoraria; Teva Pharmaceuticals: Honoraria; GSK: Honoraria; Abbvie: Honoraria; Amgen: Honoraria. Chng: Sanofi: Honoraria; Abbvie: Honoraria; Takeda: Honoraria; Amgen: Honoraria; BMS/Celgene: Honoraria, Research Funding; Johnson and Johnson: Honoraria, Research Funding; Pfizer: Honoraria.

scholarly journals Efficacy of front-line immunochemotherapy for follicular lymphoma: a network meta-analysis of randomized controlled trials

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Yucai Wang ◽  
Shouhao Zhou ◽  
Xinyue Qi ◽  
Fang Yang ◽  
Matthew J. Maurer ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Controlled Trials ◽  
Front Line ◽  
Free Survival ◽  
Randomized Controlled

Abstract Front-line treatment for follicular lymphoma has evolved with the introduction of maintenance therapy, bendamustine (Benda), obinutuzumab (G), and lenalidomide (Len). We conducted a random-effects Bayesian network meta-analysis (NMA) of phase 3 randomized controlled trials (RCTs) to identify the regimens with superior efficacy. Progression-free survival (PFS) was compared between 11 modern regimens with different immunochemotherapy and maintenance strategies. G-Benda-G resulted in with the best PFS, with an HR of 0.41 compared to R-Benda, a surface under the cumulative ranking curve (SUCRA) of 0.97, a probability of being the best treatment (PbBT) of 72%, and a posterior ranking distribution (PoRa) of 1 (95% BCI 1–3). This was followed by R-Benda-R4 (HR = 0.49, PbBT = 25%, PoRa = 2) and R-Benda-R (HR = 0.60, PbBT = 3%, PoRa = 3). R-CHOP-R (HR = 0.96) and R-Len-R (HR = 0.97) had similar efficacy to R-Benda. Bendamustine was a better chemotherapy backbone than CHOP either with maintenance (R-Benda-R vs R-CHOP-R, HR = 0.62; G-Benda-G vs G-CHOP-G, HR = 0.55) or without maintenance therapy (R-Benda vs R-CHOP, HR = 0.68). Rituximab maintenance improved PFS following R-CHOP (R-CHOP-R vs R-CHOP, HR = 0.65) or R-Benda (R-Benda-R vs R-Benda, HR = 0.60; R-Benda-R4 vs R-Benda, HR = 0.49). In the absence of multi-arm RCTs that include all common regimens, this NMA provides an important and useful guide to inform treatment decisions.

Sign in / Sign up

Export Citation Format

Share Document