Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation

Blood ◽  
2001 ◽  
Vol 97 (1) ◽  
pp. 101-106 ◽  
Author(s):  
P. Colombat
Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4370-4370
Author(s):  
Marion Alcantara ◽  
Jehan Dupuis ◽  
Michel Meignan ◽  
Anne Julian ◽  
Stephanie Becker ◽  
...  

Abstract Introduction First-line immunochemotherapy followed by two years of rituximab (R) maintenance is now the standard of care for high-tumor burden follicular lymphoma (FL). In spite of an old controversy regarding the heterogeneous metabolic activity of FL lesions, either interim or final PET-CT after R-CHOP first-line therapy is now recognize to be strongly predictive of outcome. At the time of relapse, R-chemotherapy and autologous stem cell transplantation (ASCT) is a recommended option. Though, some patients will relapse quickly while others achieve long-term remissions. We investigated the prognostic value of PET-CT in patients with high-tumor burden relapsed FL treated with salvage R-chemotherapy followed by ASCT. Patients and Methods Seventy-five patients with relapsed FL referred to three French institutions were retrospectively analyzed. Patients with grade 3b follicular lymphoma or transformed into diffuse large B-cell lymphoma were excluded. Patients received second-line immunochemotherapy according to the local physician’s choice. We classified these salvage treatments into three groups: fludarabine-based regimen (n=29, group 1), cytarabine-based regimen (n=31, group 2), or ifosfamide-based regimen (n=15, group 3). PET-CT scans performed after salvage therapy (before ASCT) were included in the analyses. The local investigator’s interpretation of the imaging physician’s scan report defined a positive or negative PET. Results Median age was 56 years and 60% were men. Sixty eight patients received ASCT. Among this whole high-risk study population, 87% relapsed before 36 months after R-CHOP and 42% relapsed within 6 months and were therefore considered as R-CHOP refractory, with a median progression free survival (PFS) after R-CHOP first-line therapy of 15 months. Only 21% of the patients received R maintenance after R-CHOP. PET-CT scans after salvage therapy (before ASCT) were considered negative in 57%/76%/47% among the 3 groups respectively (p=0.06). Median stem cell harvest was higher in group 3-ifosfamide-based (8.3.106) than in both fludarabine and cytarabine-based regimens (4.47 and 4.8.106 respectively, Mann-Whitney p=0.15). Conditioning regimen was BEAM (37%) or Zevalin-BEAM (56%). Thirteen patients received R maintenance after ASCT. At a median follow-up of 28 months, 26/75 patients relapsed and 62 are alive. At 2 years, median PFS was 63.8%/66%/53.5% and median overall survival (OS) 68%/94%/92% among the 3 groups, respectively. PFS was only correlated to PET-CT results (p=0.0006). OS was correlated to group of therapy (2-3 versus 1), FLIPI score at relapse and PET-CT negativity. The latter was the strongest OS predictor on a multivariate analysis (p<0.01). On the other hand, age, gender, conditioning regimen, and PFS after R-CHOP (<36 months or even <12 months) were not linked to shorter PFS/OS. We observed 12% of second non-hematologic cancer. Conclusion PET-CT scan negativity after salvage treatment is the most important favourable factor for relapsed/refractory FL patients who receive ASCT. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-15
Author(s):  
Ali McBride ◽  
Daniel O. Persky

Introduction: The choice of initial therapy in follicular lymphoma can be a key determinant in future therapy, as irreversible toxicities with first line regimens can impact the patient's ability to tolerate future treatment. Minimizing drug exposure will result in less frequent occurrence of significant adverse events and associated treatment costs. In the era of COVID-19 pandemic, there is additional benefit to minimizing the number of patient visits and hospital admissions. Limited information exists related to the outcomes and associated costs of existing treatment sequences. Additionally, treatment administration at different types of clinical sites results in varied reimbursement models, making informed evaluation of clinical and financial evidence challenging. Methods: The current study applies a budget impact model methodology in order to describe the associated impact of treatment selection and sequencing on outcomes and costs in the treatment of relapsed or refractory low-grade follicular lymphoma in first line therapy followed by Consolidation and also in first line therapy to second line therapy. Key model inputs included: Number of treatment cycles, number of days a treatment was received, duration of response (DOR), rate of side effects and associated costs, and total treatment costs, including drugs, medical treatment, laboratory testing and adverse event costs. Treatment outcomes were based on the published literature that summarized the overall response rate, median DOR, and toxicity. Treatment regimen costs were evaluated based on payer pricing, Wholesale Acquisition Cost (WAC), Average Selling Price (ASP) and Average Wholesale Price (AWP) and modified to adjust for weight-based dosing and negotiate payer reimbursement rates. Associated medical costs for medical treatment and supportive care were estimated using current Medicare fee schedule rates. Included were seven options for first line therapy of follicular lymphoma from 2020 NCCN Guidelines - (Bendamustine + rituximab (BR); Bendamustine + Obinutuzumab (OB); CHOP rituximab (RCHOP); CHOP + Obinutuzumab (OCHOP); CVP+ rituximab (RCVP); CVP + Obinutuzumab (OCVP); Lenalidomide + rituximab (R2)), followed by three for Consolidation (Rituximab maintenance (RM); Obinutuzumab maintenance (O); Radioimmunotherapy (RIT with 90 Y-ibritumomab tiuxetan (Y90-IT, Zevalin)) and three Second Line therapy options (RIT; Lenalidomide only; Lenalidomide + Obinutuzumab (LO)). Results: The treatment sequence of first line BR followed by Consolidation with RIT Y90 (Zevalin) had the longest predicted DOR (2586 days). The associated treatment sequence costs were $212,485 for BR followed by Y90-IT, compared with $233, 388 for BR followed by rituximab maintenance, which had a predicted DOR of 2478 days. The predicted DOR for treatment sequences starting with OCHOP, OCVP and RCHOP and followed by RIT with Y90-IT was approximately 1000 days less than BR followed by Y90-IT for a cost difference of $4,421, $12,914 and $25,826, respectively. The treatment sequence of first line BR followed by Second Line RIT Y90-IT had the second longest predicted DOR of 2586 days at costs of $212,485, compared to 2778 days for BR followed by LO, at a total sequence costs of $796,695. Conclusion: The use of Y90-IT in Consolidation or Second Line treatment demonstrated desired patient outcomes at one of the lowest cost profiles. Additionally, Y90-IT administration can be completed in only two clinic visits, reducing patient travel and contact, improving safety in an era of COVID-19 precautionary measures and reducing cost. Figure 1. Duration of Response and Total Sequence Costs for Twelve First Line to Consolidation and First Line to Second Line Treatment Regimens. Disclosures McBride: Merck: Speakers Bureau; Coherus BioSciences: Consultancy, Speakers Bureau; Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy; MorphoSys: Consultancy; Sandoz: Consultancy.


Blood ◽  
2020 ◽  
Vol 135 (24) ◽  
pp. 2133-2136 ◽  
Author(s):  
Christopher R. Flowers ◽  
John P. Leonard ◽  
Nathan H. Fowler

Abstract Lenalidomide is an immunomodulatory drug approved in the United States for use with rituximab in patients with relapsed/refractory follicular lymphoma. We reviewed data from trials addressing the safety and efficacy of lenalidomide alone and in combination with rituximab as a first-line therapy and as a treatment of patients with relapsed/refractory follicular lymphoma. Lenalidomide-rituximab has been demonstrated to be an effective chemotherapy-free therapy that improves upon single-agent rituximab and may become an alternative to chemoimmunotherapy.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5207-5207
Author(s):  
Sadao Aoki ◽  
Jun Takizawa ◽  
Masutaka Higashimura ◽  
Akihito Momoi ◽  
Nobuhiro Tsukada ◽  
...  

Abstract Introduction: Most patients with advanced-stage follicular lymphoma(FL) cannot be cured by conventional chemotherapy and have median survival of 7 to 10 years. High-dose chemotherapy (HDT) supported by autologous stem cell transplantation(ASCT) gives a survival benefit for patients with aggressive lymphoma. Recent several multicenter studies have shown that clinical and molecular remissions can be attained in patients with FL receiving intensified high-dose sequential chemotherapy and autografting. We have reported the efficacy and safety of high-dose bi-weekly THP-COP with G-CSF support (HDBW-TCOPG) for non-Hodgkin’s lymphoma. Therefore, we performed a pilot clinical trial to evaluate the efficacy and toxicity of HDBW-TCOPG followed by HDT with ASCT as first-line therapy in patients with advanced-stage FL. Patients and methods: Between August 1998 and December 2003, 10 Japanese patients with previously untreated FL from whom informed consent was obtained were included in this single-center pilot study. Median age was 48 years. All patients had stage 3 or 4 disease, aaIPI LI 8 and HI 2. Histological subtypes of FL included grade 1 4; grade 2 4; grade 3a 2. HDBW-TCOPG consisted of pirarubicin 70 mg/m2 on day 1; cyclophosphamide 1000 mg/m2 on day 1; vincristine 1.4 mg/m2 on day 1; predonisolone 50 mg/m2 from day 1 to 5; lenograstim 2.0 mg/kg/day from day 3. Five patients who enrolled after rituximab was approved for indolent B-cell lymphoma in Japan received induction therapy combined HDBW-TCOPG with rituximab 375mg/m2 on day -2 (R-HDBW-TCOPG). Six cycles were administered at intervals of two weeks. PBSC were collected during the later cycles of HDBW-TCOPG or on the recovery of high-dose etoposide regimen (500mg/m2 for 3 days) administered after the completion of HDBW-TCOPG. Leukaphereses were performed until a minimum of 2.0x106/kg CD34+ cells had been collected. The conditioning regimen consisted of ranimustine 200mg/m2 on day-7 and -2; paraplatin 300mg/m2 on day -6, -5, -4, -3; etoposide 500mg/m2 on day −5, −4, −3; cytarabine 2.5 g/m2 every 12 hours on day −2, −1 (MCE-CA regimen) in 2 patients or cyclophosphamide 50mg/kg on day −2, −1 (MCEC regimen) in 8 patients. Results: Sufficient numbers of PBSC were collected in 5 of 7 patients mobilized with HDBW-TCOPG and in all 5 patients with high-dose etoposide. The median time to reach total number of leukocytes of 1.0 x109/l was nine days (range 8–11). All 10 patients who were in PR at the end of HDBW-TCOP(G) achieved CR post APBSCT. After a median follow up of 36.6 months (range 7–66 months) PFS and OS are 90% and 90%, respectively, for all patients. One patient developed secondary myeloid leukemia with t(3;21) and died at 35 months after APBSCT without signs of recurrence of lymphoma. Another patient who relapsed at 35 months after transplantation. IgH or BCL2 rearrangement was detected by PCR analysis prior to therapy in three patients and one of them still showed detectable disease after HDBW-TCOPG induction. However, all three patients demonstrated MRD negativity after HDT with ASCT. Conclusion: HDBW-TCOPG as induction therapy followed by HDT with ASCT is feasible for advanced-stage FL with acceptable toxicity, and this short term highly intensified therapy may induce cure of the disease by minimizing MRD, but longer follow up is needed to evaluate the impact on survival.


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