scholarly journals LGG-04. A PHASE II RE-TREATMENT STUDY OF SELUMETINIB FOR RECURRENT OR PROGRESSIVE PEDIATRIC LOW-GRADE GLIOMA (pLGG): A PEDIATRIC BRAIN TUMOR CONSORTIUM (PBTC) STUDY

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii367-iii367
Author(s):  
Jason Fangusaro ◽  
Arzu Onar-Thomas ◽  
Shengjie Wu ◽  
Tina Young Poussaint ◽  
Roger Packer ◽  
...  
Keyword(s):  
Stable Disease ◽  
Pediatric Brain Tumor ◽  
Progression Free Survival ◽  
Design Parameters ◽  
Low Grade ◽  
Duration Of Treatment ◽  
Acneiform Rash ◽  
Long Term Follow Up ◽  
Grade 3

Abstract The PBTC conducted a re-treatment study (NCT01089101) evaluating selumetinib (AZD6244, ARRY-142886), a MEK I/II inhibitor, in children with recurrent/progressive pLGG. Eligible patients must have previously enrolled on PBTC-029 or PBTC-029B and progressed after coming off treatment with selumetinib. Patients must have maintained stable disease (SD) for ≥12 courses or had a sustained radiographic response (partial or complete) during their first exposure to selumetinib. Thirty-five eligible patients (median age: 13.11 years [range 7.96–25.33]) were enrolled, 57% of whom had optic pathway or hypothalamic target lesions. At the time of submission, median duration of treatment was 18 courses (range 2–48) and 21 subjects remained on therapy. Best responses reported to date are 6/35 (17%) partial response, 22/35 (63%) SD and 7/35 (20%) progressive disease with a 2-year progression-free survival of 75.7 + 8.3%, which met the design parameters for success. The most common attributable toxicities were grade 1 diarrhea, elevated AST, hypoalbuminemia, elevated CPK, maculo-papular rash, fatigue, paronychia, ALT elevation, acneiform rash and grade 2 CPK elevation. Rare grade 3 toxicities included CPK elevation (3), lymphopenia (2), paronychia (2) and ALT elevation (2). There was only one grade 4 CPK elevation. Five patients (14%) required dose reductions due to toxicity. There does not appear to be a notable difference in toxicities observed during initial selumetinib therapy versus re-treatment. In pLGG that has recurred/progressed following treatment with selumetinib, re-treatment with selumetinib appears to be effective with 80% of patients again achieving response or prolonged stable disease. Long-term follow-up is ongoing.

Long-term follow-up results of a phase I/II study of concurrent chemoradiotherapy for localized nasal NK/T-cell lymphoma (NKTCL): JCOG0211.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8050-8050
Author(s):  
Motoko Yamaguchi ◽  
Kensei Tobinai ◽  
Masahiko Oguchi ◽  
Naoki Ishizuka ◽  
Yukio Kobayashi ◽  
...  
Keyword(s):  
Phase I ◽  
Concurrent Chemoradiotherapy ◽  
Elevated Serum ◽  
Progression Free Survival ◽  
Disease Recurrence ◽  
Newly Diagnosed ◽  
Long Term Follow Up ◽  
Grade 3

8050 Background: Concurrent chemoradiotherapy has been regarded as one of the standard management for localized nasal NKTCL. However, its long-term efficacy and toxicity is not known. Methods: The JCOG0211 trial is a phase I/II study of concurrent chemoradiotherapy consisting of radiotherapy (RT) of 50 Gy and 3 cycles of DeVIC (carboplatin, etoposide, ifosfamide, dexamethasone) for newly diagnosed, localized nasal NKTCL (JCO 2009). Patients (Pts) with newly diagnosed, localized diseases (IE & contiguous IIE with cervical node involvement) who were 20-69 yrs of age with PS 0-2 were eligible. 3-D conformal RT planning with a wide margin (+ 2 cm to the gross tumor, the entire nasal cavity and the nasopharynx) and a 2-step cone down were required. 33 pts were enrolled in the study, 27 of whom were treated with RT and a 2/3-dose of DeVIC, which was selected as the recommended phase II dose in the preceding phase I portion of the trial. All pts completed RT without any protocol violations. Long-term follow-up results on overall survival (OS), progression-free survival (PFS) and toxicity were evaluated. Results: The median follow-up was 69 months (range, 62-96). The pt (N=33) characteristics were as follows: median age 54 yrs (range, 21-68); stage IIE 33%; B symptom (+) 36%; elevated serum LDH 21%. %5-yr OS and PFS were 73% (95%CI, 54-85%) and 67% (95%CI, 48-80%), respectively. 11 pts (33%) experienced disease recurrence. Two achieved a 2nd CR by salvage chemotherapies followed by allogeneic stem cell transplantation, and the remaining 9 pts died of disease. There was no observed death and disease progression after 34 and 31 months, respectively. One pt experienced Grade 3 irregular menstruation for 3 years. No other Grade 3 or 4 late non-RT-associated adverse events (AEs) were observed. One pt received plastic surgery due to Grade 4 RT dermatitis. No other Grade 3 or greater RT-associated late AEs were encountered. Conclusions: Both survival benefit and disease control from concurrent chemoradiotherapy with RT and DeVIC are maintained during a 5-yr follow-up, indicating the excellent efficacy of this approach as a first-line therapy for localized nasal NKTCL. Long-term toxicity is acceptable.

Long-term follow-up of previously untreated patients (pts) with chronic lymphocytic leukemia (CLL) treated with ofatumumab (OFA) and chlorambucil (CHL): Final analysis of the phase 3 COMPLEMENT 1 trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7528-7528
Author(s):  
Fritz Offner ◽  
Tadeusz Robak ◽  
Ann Janssens ◽  
Govind Babu Kanakasetty ◽  
Janusz Kloczko ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Final Analysis ◽  
Lymphocytic Leukemia ◽  
Primary Analysis ◽  
Free Survival ◽  
Anti Cancer ◽  
Long Term Follow Up ◽  
Grade 3

7528 Background: Previously in the COMPLEMENT 1 study, treatment with OFA and CHL in pts with untreated CLL had shown a significant improvement in the progression-free survival (PFS) compared with CHL alone, and was well tolerated. Here, we report the final overall survival (OS) analysis of the 5-year (y) follow-up, updated investigator-assessed PFS and safety from the study. Methods: Untreated pts, not fit for fludarabine-based therapy (due to advanced age or co-morbidities) were randomized 1:1 to OFA+CHL or CHL alone. Pts in OFA+CHL arm received OFA (Cycle 1: 300 mg day (d) 1, 1000 mg d8; subsequent cycles: 1000 mg d1) in addition to CHL (10 mg/m2, d1-7) for 3 to 12 cycles of 28 d each. Pts in CHL arm received CHL only. Results: Overall, 447 pts were randomized to OFA+CHL (n = 221) or CHL (n = 226); 168 (76%) and 164 (73%) pts completed the scheduled treatments, respectively. Baseline characteristics were similar in both arms. The investigator-assessed median PFS was 23.4 months (mos) in the OFA+CHL arm and 14.7 mos in the CHL arm (HR: 0.61 [95% CI 0.49, 0.76], p < 0.001). Median OS could not be estimated for the OFA+CHL arm and was 84.7 mos for the CHL arm (HR: 0.88 [95% CI 0.65, 1.17], p = 0.363). Estimated OS rate (95% CI) at 5 y was 68.5% (61.5%, 74.5%) in the OFA+CHL arm, and 65.7% (58.6%, 71.9%) in the CHL arm. Post-treatment anti-cancer therapy after discontinuation was received by a greater proportion of pts in the CHL (66%) vs. OFA+CHL (56%), and started earlier in the CHL arm (486 d) vs. OFA+CHL (743 d) arm. Overall, 84 (39%) pts in the OFA+CHL, and 99 (44%) pts in the CHL arms died during the study with 5 on-treatment deaths in each group. Grade ≥3 adverse events were seen in 64% and 48% of pts in the OFA+CHL vs. CHL arms, respectively, most common being (≥5% in either arm) neutropenia (26% vs. 15%), thrombocytopenia (5% vs. 10%), pneumonia (9% vs. 5%), and anemia (5% vs. 5%). Conclusions: This 5-y survival follow-up analysis supported the results from primary analysis with an estimated 12% (not significant) and 39% risk reduction in OS and PFS, respectively, in the OFA+CHL arm compared with the CHL arm. No new safety concerns were observed in the OFA+CHL arm. Clinical trial information: NCT00748189.

Long-term follow-up of patients (pts) with relapsed or refractory (r/r) follicular lymphoma (FL) treated with copanlisib.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7553-7553
Author(s):  
Sirpa Leppä ◽  
Armando Santoro ◽  
Judit Demeter ◽  
George Follows ◽  
Georg Lenz ◽  
...  
Keyword(s):  
Adverse Events ◽  
Median Duration ◽  
Kinase Inhibitor ◽  
Late Onset ◽  
Progression Free Survival ◽  
Duration Of Treatment ◽  
Primary Analysis ◽  
Long Term Follow Up

7553 Background: The pan-class I phosphatidylinositol 3-kinase inhibitor copanlisib was approved by the FDA in September 2017 for treatment of relapsed FL based on results from the CHRONOS-1 study in pts with indolent non-Hodgkin lymphoma. We report efficacy and safety results of a 2-year (yr) follow-up of FL pts. Methods: Pts with indolent FL (grade [G] 1-3a) r/r to ≥2 prior lines of treatment received copanlisib (60 mg i.v. infusion) on days 1, 8, and 15 of a 28-day cycle. The primary endpoint was objective tumor response rate (ORR) per independent radiologic review (Cheson et al. 2007). Adverse events were reported using MedDRA (v20.1). Data cut-off: February 20, 2018. Results: 104 FL pts were enrolled. Median age was 62 yr (39% >65 yr), the median number of prior lines of anti-cancer therapy was 3 (range 2-8), and 27 pts (26%) were classified as having G3a disease. The ORR was 59%, with complete responses (CR) in 20% ( n=21); 14 pts had a CR at the primary analysis in June 2016. The median duration of response (mDoR) was 12.2 months (mo) (range 0.03-43 mo). Stable disease (SD) was observed in 33% of pts; median duration of SD was 7.8 mo (range 1.3-23 mo). Median progression-free survival (mPFS) was 11.2 mo (range 0.03-44 mo) with 33% alive and progression-free at 2 yrs. Median overall survival (mOS) was 3.2 yr (range 0.06-4.2 yr) with 67% alive at 2 yrs. Median duration of treatment was 26 weeks (wk) (range 1-192 wk); median duration of safety follow-up was 29 wk. In the G3a subset, the ORR was 67% (26% CR), mDoR was 10.9 mo, mPFS was 12.5 mo, and mOS was 2.5 yr. The most common treatment-emergent adverse events occurring in >25% of pts included (all grade/G3+): diarrhea (37%/9%), neutropenia (26%/23%), and pyrexia (28%/5%). Hyperglycemia (49%/40%) and hypertension (29%/23%) were transient. Incidences of pneumonitis (6.7%/1.9%) and colitis (1.0% G4) were low. Conclusions: Long-term follow-up of r/r FL pts treated with copanlisib revealed robust and durable responses with CRs exceeding 20%, including in pts with higher grade disease. The safety profile continues to be both manageable and favorable, with no evidence of late-onset severe toxicities. Clinical trial information: NCT01660451.

Long Term Follow-Up and Retreatment of Patients with Low-Grade Lymphoproliferative Disorders (LPD) after 1 Year of Phamacokinetic (PK) Based Maintenance Therapy with Rituximab.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4479-4479
Author(s):  
Jennifer R. Duff ◽  
James W. Lynch
Keyword(s):  
Maintenance Therapy ◽  
Progression Free Survival ◽  
Complete Response ◽  
Subsequent Treatment ◽  
Entire Group ◽  
Published Data ◽  
Low Grade ◽  
Long Term Follow Up

Abstract Background: We previously published data from a PK based maintenance trial in patients with CD 20 positive LPD. The PK based schedule derived from that trial was 1 dose every 3 months and is currently being evaluated in a large randomized trial (ECOG 4402). There has been appropriate concern that offering maintenance therapy may select for tumor cells resistant to rituximab thereby compromising the chance of response if patients are retreated once relapsing after such therapy. We now present long term follow-up on patients with low grade LPD treated on that trial. We furthermore report the results of retreating 5 patients who initially responded but relapsed after one year of maintenance rituximab. Methods: Patients with CD20 positive LPD (except SLL/CLL) were treated with four weekly infusions of rituximab 375mg/m2. All patients without PD were then monitored for 1 year and received a single infusion of 375mg/m2 when the level fell below <25mcg/ml. Among 22 patients with low grade LPD 10 (45%) achieved a complete response and 5 (23%) a partial response for an overall response rate with 68%. With a minimal follow-up of 69 months, all but 2 patients have sufficient data available to evaluate their subsequent treatment and response. Results: Of the 22 patients, there were 18 with follicular lymphoma, 2 with lymphoplasmacytoid lymphoma and 1 each with MALT and NOS. The median progression free survival (PFS) for the entire group was 23 months, but for responders the PFS was 50 months. 6/22 (27%) remain in continuous complete remission with no further therapy with a median follow-up of 72.5 mo. (range 69–76). Nine patients who initially responded have subsequently relapsed and were treated at the discretion of the treating physician as follows: 2 received no treatment one of whom experienced a spontaneous CR lasting 59 months, one patient with an isolated CNS relapse received intrathecal and local radiotherapy and is currently in CR with no further therapy at 71mo, 1 patient died in PR of a presumed MI and 5 received retreatment with rituximab accompanied by 2 years of maintenance therapy given as 1 dose every 3 months. Of the 5 patients who were retreated with rituximab the outcomes are listed in table I. Conclusions: Individualized PK dosing for rituximab for 1 year yielded 27% prolonged DFS in patients with LG LPD. Although the numbers of patients treated are very small, 80% of those who responded to rituximab and subsequently relapsed retained sensitivity to rituximab and have had durable benefits, comparable to their first course. Future trials which evaluate the efficacy of limited duration maintenance strategies should continue follow-up of patients after progression to determine whether subsequent treatment with rituximab offers clinical benefit. Table I Patient # 1st PFS 2nd Response 2nd PFS 1 18mo CR 44mo+ 2 23mo NR NA 3 27mo CR 33mo 4 29mo CR 33mo+ 5 50mo PR 29mo+

Health-Related Quality of Life in Stable, Long-Term Survivors of Low-Grade Glioma

2015 ◽  
Vol 33 (9) ◽  
pp. 1023-1029 ◽  
Author(s):  
Florien W. Boele ◽  
Linda Douw ◽  
Jaap C. Reijneveld ◽  
Rianne Robben ◽  
Martin J.B. Taphoorn ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Stable Disease ◽  
Low Grade ◽  
Sf 36 ◽  
Related Quality ◽  
Long Term Follow Up ◽  
Health Related

Purpose Patients with low-grade glioma (LGG) often experience long periods of stable disease, emphasizing the importance of maintaining good health-related quality of life (HRQOL). We assessed the changes in HRQOL in long-term survivors of WHO grade I or II astrocytoma, oligodendroglioma, or oligoastrocytoma with clinically and radiologically stable disease. Patients and Methods Patients completed self-report measures of generic HRQOL (Short Form-36 [SF-36]) and disease-specific HRQOL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Brain Cancer Module). Assessments took place at midterm and long-term follow-up, on average 6 and 12 years after histologic diagnosis and initial treatment, respectively. Comparisons between patients with LGG and individually matched healthy controls were made, and change within the patients with LGG was calculated, as was minimal detectable change. Results Although no statistically significant differences between patients with LGG and healthy matched controls were found at midterm follow-up, patients with LGG had worse physical role functioning (P = .004) and general health perceptions (P = .004) than controls at long-term follow-up. Within patients with stable LGG (n = 65), physical HRQOL (the SF-36 physical component summary and the physical functioning subscale) was significantly worse at long-term than at midterm follow-up (both P < .001). Although 48% of patients improved or remained stable on all HRQOL scales, 38.5% of patients experienced detectable decline on one or more scales. Conclusion Although HRQOL remains mostly preserved in the majority of patients with LGG, a subset of patients experience detectable decline on one or more HRQOL scales despite long-term stable disease. For this subgroup, further research is recommended to better aid patients in dealing with the consequences of LGG.

Tislelizumab (BGB-A317) for relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL): Long-term follow-up efficacy and safety results from a phase 2 study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19507-e19507
Author(s):  
Yuqin Song ◽  
Quanli Gao ◽  
Huilai Zhang ◽  
Lei Fan ◽  
Jianfeng Zhou ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Cell Transplant ◽  
Upper Respiratory Tract ◽  
Phase 2 ◽  
Phase 2 Study ◽  
Long Term Treatment ◽  
Long Term Follow Up ◽  
Grade 3

e19507 Background: Tislelizumab is a humanized IgG4 monoclonal antibody with high affinity/specificity for programmed cell death protein 1 (PD-1). It was engineered to minimize binding to Fc-γ receptors on macrophages, thereby decreasing antibody-dependent phagocytosis, a potential mechanism of T-cell clearance and resistance to anti–PD-1 therapy. Tislelizumab therapy was highly active in autologous stem cell transplant (ASCT)-failed or ineligible patients with R/R cHL ( Leukemia. 2020;34:533). Here we report results from up to 3 years follow-up. Methods: This asingle-arm, multicenter phase 2 study (NCT03209973) of 200 mg tislelizumab administered intravenously to patients (pts) with R/R cHL every 3 weeks until progressive disease (PD) or unacceptable toxicity. Patients were eligible if they: failed to achieve a response or progressed after ASCT, or: received ≥2 lines of prior systemic chemotherapy for cHL and were ineligible for ASCT. Primary endpoint was overall response rate (ORR) assessed by an independent review committee (IRC) per Lugano criteria ( J Clin Oncol. 2014;32:3059). Secondary endpoints were progression-free survival (PFS), duration of response (DOR), complete response (CR) rate, and time to response (TTR) per IRC, safety, and tolerability. Results: Pts (N=70) from 11 centers in China were enrolled and treated; characteristics have been previously reported. As of the data cutoff date (Nov 2, 2020), median follow-up was 33.8 months (range, 3.4-38.6). Pts still on treatment at the end of study (n=33; 47.1%) entered a long-term extension study. Efficacy data is presented in the Table below. In the 13 pts who received prior ASCT, 11 (84.6%) achieved CR. The most common treatment-emergent adverse events (AEs; ≥30%) were pyrexia (57.1%), upper respiratory tract infection (38.6%), hypothyroidism (37.1%), and increased weight (34.3%). Treatment-related grade ≥3 AEs (≥2 pts) were pneumonitis, hypertension, neutropenia, lipase increased, weight increased, and increased creatine phosphokinase (CPK; 2.9% each). Immune-related AEs were reported in 32 pts (45.7%), with grade ≥3 AEs in 8 pts (11.4%): pneumonitis (4) and skin adverse reactions, nephritis, lipase increased, and blood CPK increased (1 each). AEs led to treatment discontinuation in 6 pts (8.6%). Conclusions: Long-term follow-up of R/R cHL pts treated with tislelizumab further demonstrated the substantial therapeutic activity and continued PFS benefit. There were no new safety concerns identified for long-term treatment with tislelizumab. Clinical trial information: NCT03209973. [Table: see text]

Predictors for survival with cabazitaxel (CBZ) in metastatic, castration-resistant prostate cancer (mCRPC): Long term follow-up of the Spanish registry.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e602-e602
Author(s):  
Iria González-Maeso ◽  
Nuria Lainez ◽  
Daniel Castellano ◽  
Iciar Garcia Carbonero ◽  
Pablo Borrega ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Therapeutic Benefit ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant ◽  
Long Term Follow Up ◽  
Baseline Characteristics ◽  
Grade 3

e602 Background: The clinical experience with CBZ in mCRPC patients (pts) has enriched notably since its approval for clinical use, but there is still a lack of well-defined prognostic/predictive factors to better characterize the profile of pts that could achieve the best therapeutic benefit. Analysis of the final expanded cohort and mature long-term follow-up are presented. Methods: Medical records from mCRPC pts progressing during or after docetaxel and treated with CBZ at 21 centres in Spain were reviewed retrospectively. Baseline characteristics, overall survival (OS), radiographic progression-free survival (rPFS), and toxicity were collected. Univariate and multivariate analysis of a variety of factors predicting OS were conducted. Results: 187 consecutive pts (median age 69) with intermediate-poor prognostic baseline characteristics (Table 1) received a median of 6 cycles (range 2-59) of CBZ. Median OS from first CBZ cycle was 15.3 [CI: 11.7; 18.0] months (mo) and median clinical and/or rPFS was 7.9 mo [CI: 6.8; 10.3]. Gleason score (GS) < 8 (vs ≥ 8), time under first-line androgen deprivation therapy (ADT) ( > 16.1 (median) vs < 16.1 mo) and the number of chemotherapy lines before CBZ did not significantly influence OS. Median follow-up was 9.5 mo. Febrile neutropenia occurred in 4 pts and 1 pt had neutropenic infection. Main nonhematologic grade ≥ 3 toxicities were asthenia (2.7%) and diarrhea (1.6%). Alopecia, nails disorders and peripheral neuropathy were uncommon. Conclusions: CBZ administered in the daily clinical practice is associated with consistent OS, similar to that observed in pivotal clinical trials. GS, median time under first-line ADT and number of chemotherapy lines before CBZ did not influence clinical benefit. CBZ has an acceptable safety profile. Funding: Sanofi [Table: see text]

Nivolumab (NIVO) + low-dose ipilimumab (IPI) in previously treated patients (pts) with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Long-term follow-up.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 635-635 ◽  
Author(s):  
Michael J. Overman ◽  
Sara Lonardi ◽  
Ka Yeung Mark Wong ◽  
Heinz-Josef Lenz ◽  
Fabio Gelsomino ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Low Dose ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Long Term Follow Up ◽  
Previously Treated ◽  
Grade 3

635 Background: In the phase II CheckMate-142 trial, NIVO + low-dose IPI (1 mg/kg) provided meaningful clinical benefit in previously treated MSI-H/dMMR mCRC pts after a median follow-up of 13.4 mo. Here, we present long-term follow-up (median 25.4 mo) of these pts. Methods: Pts received NIVO 3 mg/kg + low-dose IPI Q3W (4 doses) followed by NIVO 3 mg/kg Q2W until disease progression. Primary endpoint was investigator (INV)-assessed objective response rate (ORR; RECIST v1.1). Results: Of 119 treated pts, 76% had ≥ 2 prior lines of therapy. ORR and disease control rates (DCR) were 58 and 81%, respectively (Table). Complete response (CR) rate increased with long-term follow-up from 3 (13.4 mo) to 6% (25.4 mo). Median duration of response (DOR) was not reached, with 68% of responses ongoing at data cutoff. At 24 mo, progression-free survival (PFS) and overall survival (OS) rates were 60 and 74%, respectively; OS rates were 96, 56, and 29% in pts with CR or partial response (PR), stable disease (SD), and progressive disease (PD), respectively. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 31% of pts; 10% (grade 3–4) and 13% (any grade) of pts had TRAEs leading to discontinuation. Conclusions: Long-term follow-up with NIVO + low-dose IPI provides durable clinical benefit with deepening of response and a manageable safety profile with no new safety signals, demonstrating long-term benefit of NIVO + low-dose IPI for previously treated pts with MSI-H/dMMR mCRC. Clinical trial information: NCT02060188. [Table: see text]

scholarly journals Long-Term Outcome of Patients with Low-Grade Follicular Lymphoma Treated with Yttrium-90 Ibritumomab Tiuxetan: The Mayo Clinic Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2809-2809 ◽  
Author(s):  
Muhamad Alhaj Moustafa ◽  
Ricardo Parrondo ◽  
Gregory Wiseman ◽  
Jennifer Peterson ◽  
Thomas E. Witzig ◽  
...  
Keyword(s):  
Median Time ◽  
Research Funding ◽  
Progression Free Survival ◽  
Low Grade ◽  
Ibritumomab Tiuxetan ◽  
Entire Cohort ◽  
Grade 3 ◽  
Yttrium 90

Background Follicular lymphoma (FL) is the second most common lymphoma accounting for approximately 15% of all non-Hodgkin's lymphoma (NHL). Yttrium-90 ibritumomab tiuxetan [(90)Y-IT; Zevalin] is a radio-immunoconjugate (RIC) which targets CD20. It is approved in relapsed/refractory low-grade NHL and as consolidation after upfront induction chemoimmunotherapy for FL. This study analyzed patients with previously untreated (UFL) or relapsed/refractory low-grade FL (RFL) treated at our institution with (90)Y-IT. It represents the largest reported cohort for therapeutic use of (90)Y-IT in low-grade FL. Methods Medical records of patients with low-grade FL (WHO grade 1-2) who received treatment with (90)Y-IT at Mayo Clinic Cancer Center between January 2003 and December 2018 were analyzed. Overall response rate (ORR) and complete response rate (CR) were calculated. Progression-free survival (PFS), time to next therapy (TTNT), and overall survival (OS) were analyzed using the Kaplan-Meier method. Results Our cohort consists of 137 patients - 29% (40/137) with UFL and 71% (97/137) with RFL. The median age at diagnosis was 60 years (range, 18-86) with 54% (74/137) males. The median number of previous treatments in RFL patients was 1 (range, 1-5). ECOG performance status at the time of treatment was 0 in 90% and 1 in 10% of patients. 87% (119/137) had stage III/IV disease at the time of (90)Y-IT therapy. The median follow up from the time of (90)Y-IT therapy was 10.2 years (95% CI; 8.8, 11.6); 69% (95/137) of patients are alive. The ORR was 100% in UFL with 93% (37/40) CR while ORR in UFL was 93% (90/97) with 73% (71/97) CR. 45% (48/108) of the CR patients remain in continuous CR (CCR) with a median follow-up of 7 years (95% CI; 5.2, 9.9). CCR was observed in 55% (22/40) of UFL patients compared to 27% (26/97) of RFL patients. 63% (86/137) of patients had relapsed. More relapses occurred in the RFL group (69/97; 71%) compared to the UFL group (17/40; 43%), (p=0.002). In the entire cohort, the median PFS was 2.5 years (95% CI; 2.1, 3.5) and TTNT was 3.6 years (95% CI; 2.5, 4.7). Median PFS was significantly higher in UFL group compared to RFL group- 4.1 years (95% CI; 2.3, NR) vs 2.2 years (95% CI; 1.6, 3.1), respectively (Figure 1-A). Median TTNT was higher in UFL group compared to RFL group- NR (95% CI; 4.1 years, NR) vs 2.4 years (95% CI; 2, 3.6), respectively (Figure 1-B). Median OS (entire cohort) was 18 years (95% CI; 15.8, NR) with no statistically significant difference between UFL group and RFL group; NR (95% CI; NR, NR) vs 18 years (95% CI; 12.3, 20.5), respectively (Figure 1-C). Transformation to high grade lymphoma was seen in 19% (18/97) in RFL group compared to 2.5% (1/40) in UFL group, (p=0.005). Median time to transformation was 4.3 years (range, 1-11). More patients developed therapy-related myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) in the RFL group 14% (14/97) compared to 2.5% (1/40) in the UFL group (p= 0.02). Median time to develop MDS/AML was 3.3 years (range, 0-9.7). Grade ³3 neutropenia was observed in 46% of patients with median time to recovery of 21 days (range, 2-706). Grade ³3 thrombocytopenia was observed in 47% of patients with median time to recovery of 23 days (range, 7-548). Eighteen patients required growth factors support and 14 required transfusions. Non-hematologic AEs included mild to severe fatigue in 35 patients. Conclusion Radio-immunoconjugate therapy with (90)Y-IT is an effective single-agent regimen for low-grade FL. The response and survival data in this large real-world cohort is superior to the pivotal trials of this agent conducted nearly 20 years ago. The data in untreated FL is also of interest and provides the rationale for our current randomized phase 2 trial in untreated FL (https://clinicaltrials.gov/show/NCT02320292). Long-term complete remission (>7 years) was seen in 35% of the study population. Based on these promising results, clinical trials combining RIC with novel agents that could potentiate its effects are warranted. Figure 1 (A) Progression-free survival; comparing time to progression or death after (90)Y-IT treatment between previously untreated patients (UFL) and patients with relapsed/refractory FL (RFL), (B) Time to next therapy; comparing time to starting next line of treatment after (90)Y-IT treatment between UFL and RFL, (C) Overall survival; comparing time to death from all causes after (90)Y-IT treatment between UFL and RFL. Figure 1 Disclosures Tun: DTRM Biopharma: Research Funding; TG Therapeutics: Research Funding; BMS: Research Funding; Curis: Research Funding; Celgene: Research Funding; Mundi-pharma: Research Funding. OffLabel Disclosure: Yttrium-90 ibritumomab tiuxetan [(90)Y-IT; Zevalin] is a radio-immunoconjugate (RIC) which targets CD20. It is approved in relapsed/refractory low-grade NHL and as consolidation after upfront induction chemoimmunotherapy for FL. We are discussing its use as a frontline therapy in low grade FL.

Pegfilgrastim in colorectal cancer (CRC) patients (pts) receiving every-two-week (Q2W) chemotherapy (CT): Long-term results from a phase II, randomized, controlled study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4072-4072
Author(s):  
J. R. Hecht ◽  
M. Pillai ◽  
R. Gollard ◽  
L. Dreiling ◽  
M. Mo ◽  
...  
Keyword(s):  
Study Drug ◽  
Treatment Phase ◽  
Progression Free Survival ◽  
Long Term Results ◽  
Controlled Study ◽  
Serious Adverse Events ◽  
Long Term Follow Up ◽  
Grade 3

4072 Background: Survival in advanced CRC is prolonged by adding oxaliplatin (Ox) and/or irinotecan (Iri) to Q2W 5-fluorouracil/leucovorin (5FU/LV). Combination therapy, however, has a higher incidence of febrile neutropenia (FN) and related toxicities. This study evaluated pegfilgrastim dosing on day 4 of Q2W regimens in CRC. Here we present long-term follow-up of these pts. Methods: Advanced CRC pts were randomized (1:1) to pegfilgrastim 6mg or placebo, which was stratified by CT regimen received: FOIL, FOLFOX, or FOLFIRI. We previously reported grade 3/4 neutropenia (primary endpoint) in 43% placebo and 13% pegfilgrastim pts in the 4-cycle treatment phase (odds ratio = 0.19, 95% CI: 0.10–0.37; p < 0.0001). After end of treatment, pts were followed long term for ≤ 2 years (inclusive of ≤ 8 additional cycles) for serious adverse events (SAEs), overall survival (OS), and progression-free survival (PFS). Median follow-up time was 519 days. Kaplan-Meier methods estimated OS and PFS from study day 1. The study was not powered to detect PFS or OS differences between treatment groups. Results: Of 241 pts analyzed (123 pegfilgrastim, 118 placebo), 49% received FOLFOX, 26% FOLFIRI, and 25% FOIL. In the treatment period, 8% placebo and 2% pegfilgrastim pts had grade 3/4 FN ( Table ). Pegfilgrastim was well tolerated with no dose delays attributed to leukocytosis. Pegfilgrastim and placebo had similar PFS and OS ( Table ). No SAEs related to study drug were reported in the follow-up period. Conclusions: In this randomized, placebo-controlled study, pegfilgrastim significantly lowered neutropenic risk. Bone pain incidence in this CRC population was lower than in breast cancer pts treated with a taxane (Vogel J Clin Oncol 2005); the incidence in pegfilgrastim pts was modestly increased over placebo. Leukocytosis was not a concern despite the 11-day dosing interval. Long-term results suggest similar PFS and OS in the pegfilgrastim and placebo pts in this CRC study. [Table: see text] [Table: see text]

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