Use of a multi-drug regimen gemcitabine, 5-fluorouracil, irinotecan, cisplatin bevacizumab, docetaxel and cyclophosphamide (GFIP/BDC) for heavily pretreated epithelial ovarian (EOC), Fallopian tube (FT) and primary peritoneal (PP) cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17073-e17073
Author(s):  
Melissa Schwartz ◽  
Samantha Cohen ◽  
Peter Remsen Dottino ◽  
Ann Marie Beddoe
Keyword(s):  
Adverse Events ◽  
Performance Status ◽  
Descriptive Analysis ◽  
Initial Response ◽  
Drug Regimen ◽  
Severe Neutropenia ◽  
Limiting Factor ◽  
Platinum Based Chemotherapy ◽  
Cytotoxic Treatment ◽  
Grade 3

e17073 Background: Despite initial response rates to standard platinum-based chemotherapy for EOC/FT/PP, the majority of patients relapse. The purpose of this study was to describe response and tolerability of GFIP/BDC, a modification of the G-FLIP regimen (Bruckner et al), in patients with persistent or recurrent EOC/FT/PP. Treatment consisted of a 2-day combination of gemcitabine 300mg, 5-fluorouracil 500mg/m2, irinotecan 20-30mg/m2, cisplatin 20mg/m2, bevacizumab 4mg/kg, docetaxel 20mg/m2, and cyclophosphamide 20mg/m2 administered every 14 days. Methods: A retrospective descriptive analysis of 20 patients from a single academic institution who received combination GFIP/BDC therapy from January 1, 2011 to August 31, 2016 for persistent or recurrent EOC/FT/PP. Toxicities were retrospectively graded using CTCAE v4.0. Results: Twenty patients were identified with a median age 57.5 years (range 32-71). 85% of patients were non-Hispanic white, 90% had cancer of high-grade serous histology, and all had a GOG performance status of 0-1. Patients had received a median of 3 prior regimens and 95% were platinum-resistant. Median number of cycles administered was 9 (range 3-48) and patients remained on treatment for a median of 5.1 months (range 1.5-24). Thirteen patients (65%) experienced a clinical response (1 complete, 12 partial) with a median duration of 5 months (range 1.5-20). Eight patients (45%) survived progression free for at least 6 months. Grade 3 adverse events were hematologic (5), constitutional (3), gastrointestinal (3), neurologic (2), and vascular (1). Grade 4 adverse events included severe neutropenia (1) and anaphylaxis (1). Thirteen patients (65%) experienced at least one grade 3/4 adverse event. Patients discontinued treatment due to disease progression 65% (13), toxicity 20% (4), patient preference 10% (2), and one patient (5%) is currently on treatment. Conclusions: Selected EOC/FT/PP patients who have failed multiple lines of conventional cytotoxic treatment may benefit from GFIP/BDC. Toxicity might be a limiting factor for administration.

A phase II study of rucaparib in patients with high genomic LOH and/or BRCA 1/2 mutated stage IV non-small cell lung cancer (Lung-MAP Sub-Study, S1900A).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9024-9024
Author(s):  
Jonathan W. Riess ◽  
Mary Weber Redman ◽  
Paul Wheatley-Price ◽  
Bryan A. Faller ◽  
Liza C. Villaruz ◽  
...  
Keyword(s):  
Adverse Events ◽  
Systemic Therapy ◽  
Interim Analysis ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Stage Iv ◽  
Eligibility Criteria ◽  
Phenotypic Marker ◽  
Platinum Based Chemotherapy ◽  
Grade 3

9024 Background: While prior studies have shown robust efficacy leading to FDA approval of PARP inhibitors (PARPi) in BRCA-associated cancers, data in NSCLC are much less clear. S1900A, a LUNG-MAP substudy, evaluated the PARPi rucaparib in advanced stage NSCLC harboring BRCA1/2 mutations or genomic loss of heterozygosity (LOH) as a phenotypic marker of homologous recombination deficiency (HRD). Methods: Eligible patients (pts) were required to have a deleterious mutation in BRCA1/BRCA2 and/or high (≥21%) genomic LOH. Key eligibility criteria: advanced NSCLC patients (pts) with progression on or after platinum based chemotherapy and/or PD-(L)1 antibody and progressed on most recent line of systemic therapy, a Zubrod performance status of 0-1, adequate organ function, no ≥ grade 3 hypercholesterolemia, no previous PARPi exposure and no systemic therapy within 21 days of registration. Pts stratified by histology into two cohorts (squamous [sq] and non-squamous/mixed histology [nsq]). With 40 eligible pts per cohort, the design had 91% power to rule out an ORR of 15% if the true ORR was at least 35% at the 1-sided 5% level. A planned interim analysis on the first 20 pts evaluable for response per cohort required ≥ 3 responses to proceed to full enrollment. Results: 64 pts enrolled (27 sq cohort; 37 nsq cohort) of whom 59 are eligible. Median age 65.7 yrs; M/F 33/26 (56/44%); 98% of the pts received at least 1 prior line of treatment for stage IV disease. Biomarker selection included 36 pts (61%) LOH only, 4 pts (7%) BRCA1 only, 11 pts (19%) BRCA2 only, 4 pts (7%) BRCA1 + LOH high and 4 pts (7%) BRCA2 + LOH high. Both cohorts were closed for futility with insufficient responses in the interim analysis populations. In the full study, 4 responses (3 nsq/1 sq) were reported. ORR was 7% (95% CI: 0-13) (9% nsq/4% sq) and DCR was 62% (95% CI: 50-75) (62% nsq/64% sq); 3 of the 4 responders harbored BRCA1/2 mutations and 1 of 4 high LOH; ORR in BRCA1/2+ pts 3/23 (13%). Median PFS was 3.2 months (95% CI: 1.6-4.6) in nsq cohort and 2.9 months (95% CI 1.6-6.2) in sq cohort. Median OS was 7.8 months in nsq cohort and 7.9 months in sq cohort. The most frequent grade ≥3 adverse events were anemia (22%), lymphopenia (8%), fatigue (8%) and transaminitis (5%). Conclusions: S1900A failed to show the requisite level of efficacy for rucaparib in advanced NSCLC pts with high genomic LOH and/or a BRCA1/2 mutation. There were no new safety signals and hematologic toxicities were the most frequent adverse events. Genomic LOH as a phenotypic marker of HRD does not predict sufficient activity of rucaparib in NSCLC. These results stand in contrast to the high level of efficacy of PARPi in patients with BRCA-associated or high LOH cancers of other tumor types. Underlying biologic differences in the genomic characteristics of these cancers vs. NSCLC may be responsible. Studies examining this premise are ongoing. (NCT03845296). Clinical trial information: NCT03845296.

Safety of Vinflunine in Patients with Advanced Urothelial Carcinoma Refractory to Platinum-based Chemotherapy: A Prospective Pilot Study

2019 ◽  
Vol 14 (1) ◽  
pp. 31-36
Author(s):  
Raafat Abdel-Malek ◽  
Kyrillus S. Shohdy ◽  
Noha Abbas ◽  
Mohamed Ismail ◽  
Emad Hamada ◽  
...  
Keyword(s):  
Pilot Study ◽  
Adverse Events ◽  
Urothelial Carcinoma ◽  
Transitional Cell ◽  
Chemotherapeutic Agents ◽  
Serious Adverse Events ◽  
Platinum Based Chemotherapy ◽  
Number Of Patients ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3

Background: Several single chemotherapeutic agents have been evaluated as the second-line treatment of advanced urothelial carcinoma. Despite encouraging efficacy outcomes, toxicity has often led to dose modifications or discontinuation. We aimed to assess the safety of vinflunine in a particular population of advanced transitional cell carcinoma of urothelium (TCCU), that were exposed to the previous toxicity of chemotherapy. Methods: This is an open-label, prospective, single-center pilot study to evaluate the response rate and safety profile of vinflunine in patients with advanced TCCU. It was planned to enroll 25 evaluable patients. Eligible patients are those with progressive disease after first-line platinum-based regimen for advanced or metastatic disease. Results: The study was prematurely closed due to two sudden deaths that were judged by the review board as treatment-related. Only ten patients were evaluated and received at least one cycle of vinflunine. All but one were male and seven underwent radical surgery. Eight had a distant metastasis (mainly lung and/or liver). Disease control rate was 40%, four patients had a partial response with median duration of response of 3.5 months. The median overall survival was 3.2 months (95% CI:1.67- 4.73). There were three serious adverse events namely two sudden deaths and one grade 4 thrombocytopenia. Nine grade 3/4 adverse events occurred. The most common all-grade adverse events were fatigue (50%), constipation (40%) and vomiting (40%). Moreover, grade 3 fatigue occurred in 30% of patients. Only one patient, who achieved PR for 5 months, was fit to receive further cytotoxic chemotherapy. Conclusion: The activity of vinflunine in advanced urothelial carcinoma came at the expense of its safety. The use of vinflunine has to be limited to the selected group of patients. However, this is a single institute experience in a limited number of patients.

scholarly journals Safety and Efficacy of Four Drug Versus Three Drug Regimens Among Patients with Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-3
Author(s):  
Saad Ullah Malik ◽  
Nazma Hanif ◽  
Priyanka Kumari ◽  
Khadija Noor Sami ◽  
Chase Warner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Standard Of Care ◽  
Drug Regimen ◽  
P Value ◽  
Newly Diagnosed ◽  
Drug Regimens ◽  
Grade 3

Introduction: During recent years there has been a boom in the availability of treatments for multiple myeloma (MM). Based on the status of disease (newly diagnosed or relapsed/refractory), several regimens have successfully improved progression free survival (PFS) and overall survival (OS) in these two types of patients. Triple drug regimen is considered the current standard of care for newly diagnosed MM patients. However, with the advent of four drug regimens, some studies demonstrated a significant improvement in PFS and OS compared to standard of care where as others showed marginal to no difference. Also, it remains unclear whether the benefits of using four drug regimen outweigh the risks. Thus, the aim of our meta-analysis was to compare the efficacy and safety of four drug versus three drug regimens among newly diagnosed multiple myeloma patients. Methods: We built a PICO based search strategy using keywords like "multiple myeloma", "randomized clinical trials" and ran literature search on PubMed, Embase, Wiley Cochrane Library, Web of Science and ClinicalTrials.gov ranging from the date of inception till 16th July, 2020. A pre-validated data extraction sheet was used to extract data on PFS, OS and ≥Grade 3 hematologic adverse events at the longest follow-up. We included only randomized clinical trials (RCTs) comparing four versus three drug regimen in newly diagnosed MM patients. We excluded studies other than RCTs, studies conducted on relapsed refractory MM patients or other plasma cell dyscrasias. A generic variance weighted random effects model (DerSimonian and Laird) was used to derive hazard ratio estimates along with their 95% confidence intervals (CIs) for PFS and OS. Risk ratio along with its 95% CIs was estimated for Grade ≥3 hematologic adverse events. Heterogeneity was assessed with Cochrane Q -statistic and was quantified with I2 test (I2 >50% was consistent with a high degree of heterogeneity). A pre-specified sensitivity analysis was also performed for risk of adverse events. Cochrane Collaboration's tool was used to assess the quality of included RCTs and GRADE was used to rate the quality of evidence. Results: Initial search retrieved 7622 titles. After duplicate removal, 4880 articles were left. Following initial screening, 58 articles were considered for full text review. Of these only 3 studies (n=2277) met inclusion criteria. Four drug regimens included daratumumab, bortezomib, melphalan-prednisone (D-VMP), daratumumab, bortezomib, thalidomide-dexamethasone (D-VTd) and bortezomib and melphalan prednisone and thalidomide (VMPT-VT) respectively. Whereas, three drug regimens were bortezomib, melphalan-prednisone (VMP), bortezomib, thalidomide-dexamethasone (VTd) and bortezomib, melphalan and prednisone (VMP) respectively. There was a significant improvement in PFS when 4 vs 3 drug regimens were compared in patients with newly diagnosed MM (HR: 0.53, 95% CI: 0.46-0.62, p-value:<0.001, I2: 0%). Also, OS improved significantly in four drug regimen group (HR: 0.62, 95% CI: 0.51-0.76, p-value:<0.001, I2: 3.5%). There was no statistically significant difference in any grade ≥3 hematologic adverse events when 4 vs 3 drug regimens were compared (RR: 1.26, 95% CI: 0.93-1.73, p-value:0.14, I2: 93%). Sensitivity analysis after removing D-VTd regimen from any grade ≥3 hematologic adverse events revealed similar results (RR: 1.05, 95% CI: 0.97-1.13, p-value:0.23, I2: 23%) confirming the robustness of analysis. When each hematologic adverse event was looked at separately, there was no difference between 4 vs 3 drug regimen in rates of anemia (RR: 0.99, 95% CI: 0.76-1.28, p-value:0.92, I2: 0%), neutropenia (RR: 1.39, 95% CI: 1.00-1.94, p-value:0.05, I2: 85%) and thrombocytopenia (RR: 1.13, 95% CI: 0.92-1.39, p-value:0.24, I2: 33%). There was low risk of bias and strength of evidence was of moderate. Conclusion: Using four drug regimens, compared to three drug regimens, significantly improves PFS and OS among newly diagnosed multiple myeloma patients without any difference in the risk of ≥3 grade hematologic adverse events. Further randomized clinical trials are required to establish four drug regimen as standard of care for patients with newly diagnosed multiple myeloma. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Safety and efficacy outcomes with nivolumab plus ipilimumab in patients with advanced renal cell carcinoma and low Karnofsky performance status: Results from the CheckMate 920 trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 315-315
Author(s):  
Thomas E. Hutson ◽  
Bradley Curtis Carthon ◽  
Jeffrey Yorio ◽  
Sunil Babu ◽  
Heidi Ann McKean ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Adverse Events ◽  
Clear Cell ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Objective Response ◽  
Safety And Efficacy ◽  
Grade 3

315 Background: Combination therapy with nivolumab + ipilimumab (NIVO+IPI) has demonstrated long-term efficacy and tolerability for patients (pts) with previously untreated advanced renal cell carcinoma (aRCC). Most pivotal clinical trials in pts with aRCC have excluded pts with low Karnofsky performance status (KPS; < 70%). CheckMate 920 is a multi-arm, phase IIIb/IV, open-label clinical trial of NIVO+IPI treatment in pts enrolled in a community practice setting with aRCC and a high unmet medical need. We present safety and efficacy results for the cohort of pts with aRCC of any histology and KPS 50%–60% from CheckMate 920 (NCT02982954). Methods: Pts with previously untreated advanced/metastatic RCC and KPS 50%–60% received NIVO 3 mg/kg + IPI 1 mg/kg Q3W × 4 doses followed by 480 mg NIVO Q4W for ≤ 2 years or until disease progression/unacceptable toxicity. The primary endpoint was incidence of grade ≥ 3 immune-mediated adverse events (imAEs) within 100 days of last dose of study drug. Key secondary endpoints included progression-free survival (PFS) and objective response rate (ORR) by RECIST v1.1 (both per investigator). Exploratory endpoints included overall survival (OS). Results: Of 25 treated pts with KPS 50%–60%, 76% were men; median age was 67 years (range, 34–81). IMDC risk was favorable in 0%, intermediate in 32%, and poor in 68% of pts; 84% had clear cell and 16% had non-clear cell RCC histology. With a minimum follow-up of 25 months, median duration of therapy (95% CI) was 2.3 months (2.1–7.7) for NIVO and 2.1 months (2.1–2.1) for IPI. The median number of doses (range) received was 4 (1–27) for NIVO and 4 (1–4) for IPI; 76% of pts received ≥ 4 NIVO doses and 68% received all 4 IPI doses. The only grade 3–4 imAEs by category were hepatitis (4.0%) and adrenal insufficiency (4.0%). No grade 5 imAEs occurred. Overall, 4 (16%) pts discontinued due to any-grade adverse events (n = 1 each for elevated AST, malignant neoplasm progression, back pain, and acetabulum fracture). Of 18 evaluable pts, ORR was 33.3% (95% CI, 13.3–59.0); no pts had a complete response and 6 had partial response. Median time to objective response was 4.5 months (range, 2.5–24.7). Median duration of objective response was 20.6 months (range, 0.03+–24.2+). Median PFS was 4.6 months (95% CI, 2.5–14.8). Median OS was 15.6 months (95% CI, 5.3–25.1). Conclusions: NIVO+IPI demonstrated an acceptable safety profile and promising antitumor activity in pts with previously untreated aRCC and KPS 50%–60%. The combination was tolerated at a dose intensity similar to that observed in clinical trials conducted in pts with higher KPS (≥ 70%). These data support the value of NIVO+IPI in pts who may not be considered ideal candidates for this therapy and consequently may have limited treatment options. Clinical trial information: NCT02982954 .

scholarly journals Safety and efficacy of rifabutin among HIV/TB-coinfected children on lopinavir/ritonavir-based ART

2019 ◽  
Vol 74 (9) ◽  
pp. 2707-2715 ◽  
Author(s):  
Holly E Rawizza ◽  
Kristin M Darin ◽  
Regina Oladokun ◽  
Biobele Brown ◽  
Babatunde Ogunbosi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Absolute Neutrophil Count ◽  
Neutrophil Count ◽  
Treatment Options ◽  
Severe Neutropenia ◽  
Laboratory Monitoring ◽  
Safety And Efficacy ◽  
Cell Percentage ◽  
Grade 3 ◽  
Cd4 Cell

Abstract Background TB is the leading cause of death among HIV-infected children, yet treatment options for those who require PI-based ART are suboptimal. Rifabutin is the preferred rifamycin for adults on PI-based ART; only one study has evaluated its use among children on PIs and two of six children developed treatment-limiting neutropenia. Methods Since 2009, rifabutin has been available for HIV/TB-coinfected children requiring PI-based ART in the Harvard/APIN programme in Nigeria. We retrospectively analysed laboratory and clinical toxicities at baseline and during rifabutin therapy, and examined HIV/TB outcomes. Results Between 2009 and 2015, 48 children received rifabutin-containing TB therapy with PI (lopinavir/ritonavir)-based ART: 50% were female with a median (IQR) baseline age of 1.7 (0.9–5.0) years and a median (IQR) CD4+ cell percentage of 15% (9%–25%); 52% were ART experienced. Eighty-five percent completed the 6 month rifabutin course with resolution of TB symptoms and 79% were retained in care at 12 months. Adverse events (grade 1–4) were more common at baseline (27%) than during rifabutin treatment (15%) (P = 0.006). Absolute neutrophil count was lower during rifabutin compared with baseline (median = 1762 versus 2976 cells/mm3, respectively), but only one instance (2%) of grade 3 neutropenia occurred during rifabutin treatment. Conclusions With clinical and laboratory monitoring, our data suggest that rifabutin is a safe option for TB therapy among children on PI-based ART. By contrast with the only other study of this combination in children, severe neutropenia was rare. Furthermore, outcomes from this cohort suggest that rifabutin is effective, and a novel option for children who require PI-based ART. Additional study of rifabutin plus PIs in children is urgently needed.

scholarly journals Real-world adverse events with niraparib 200 mg/day maintenance therapy in ovarian cancer: a retrospective study

2019 ◽  
Vol 15 (36) ◽  
pp. 4197-4206
Author(s):  
Jack R Gallagher ◽  
Kylee Jean Heap ◽  
Susan Carroll ◽  
Karin Travers ◽  
Brooke Harrow ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Retrospective Study ◽  
Adverse Events ◽  
Real World ◽  
Recurrent Ovarian Cancer ◽  
Medical Record Data ◽  
Platinum Based Chemotherapy ◽  
Record Data ◽  
Grade 3

Aim: To assess real-world occurrence of common clinical trial-reported adverse events (AE) among patients with recurrent ovarian cancer initiating niraparib 200 mg/day. Materials & methods: This retrospective observational study used physician-extracted anonymized medical record data of eligible patients initiating niraparib 200 mg/day after platinum-based chemotherapy. Results: Of 153 patients, 57 (37%) experienced ≥1 of the three most common all-grade AEs within 3 months after niraparib initiation: nausea (16%; grade 3/4: 2%), thrombocytopenia (14%; grade 3/4: 3%) and fatigue (24%; grade 3/4: 3%). In the ENGOT-OV16/NOVA trial, these respective AEs occurred in 74, 61 and 59% of patients. Conclusion: Incidence of common clinical trial-reported AEs was lower among patients initiating niraparib 200 mg/day in real-world practice versus patients initiating niraparib 300 mg/day in ENGOT-OV16/NOVA.

Phase II Study of Thalidomide in Escalating Doses for Follicular (F-NHL) and Small Lymphocytic Lymphoma (Sll): CALGB Study 50002.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3284-3284 ◽  
Author(s):  
David L. Grinblatt ◽  
Jeffrey Johnson ◽  
Donna Niedzwicki ◽  
David A. Rizzieri ◽  
Nancy Bartlett ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Adverse Events ◽  
Phase Ii ◽  
Performance Status ◽  
Sensory Neuropathy ◽  
Complete Response ◽  
Lymph Node Biopsy ◽  
Prior Therapy ◽  
Median Daily Dose ◽  
Grade 3

Abstract Background: Thalidomide has marked activity in both untreated and heavily pretreated myeloma. Its activity in part is believed to be due to inhibition of bFGF and VEGF induced angiogenesis. Elevated levels of bFGF in serum and urine have correlated with decreased survival in lymphoma possibly through up-regulation of BCL-2. Methods: 25 patients (pts) with previously treated F-NHL and SLL were registered and treated on this multi-institutional study from July 2001–April 2004 to evaluate the efficacy and safety of oral thalidomide in this patient group. Pts had B-cell SLL (7: 36.8%), F-NHL grade 1 (7: 36.8%), grade 2 (3: 15.8%) and grade 3 (2: 10.1%) NHL. Pts were eligible for entry with up to 3 prior chemotherapy (CT) and 2 immunotherapy (IT) regimens provided performance status was ≥ 1. Pts with new onset of B-symptoms, rising LDH, rapid tumor growth or greater than one year from initial diagnosis were required to undergo repeat lymph node biopsy to exclude recent transformation. Pts with CNS involvement, prior peripheral neuropathy >gr 1, HIV+, and pregnant or nursing women were also excluded. Pts were required to have Cr <2 x ULN, AST/ALT <2.5 x ULN and an ANC > 750. Median age at study entry was 60 years (36–87). Prior therapy was evaluated in 20 pts and 17/20 had received multi-agent CT while 12/20 pts received prior IT. Thalidomide was initiated at a dose of 200 mg daily and escalated by 100 mg daily every 1–2 weeks as tolerated with a maximal dose of 800 mg/d. If ≥ gr 2 peripheral neuropathy or ≥ gr 3 somnolence or mood changes occurred, the dose was held for one week and restarted at 50% of the prior daily dosage. Results: The median daily dose was 400 mg (range 50–800 mg). There was 1 complete response (CRu-residual abnormality) in a pt with SLL and one partial response in a pt with F-NHL grade 1 (ORR 8%: 95%CI: 1–26%). 16 pts had progressive disease during therapy and 2 died of disease soon after stopping therapy due to adverse events. One patient continues on therapy without progression of disease to date. The remaining 4 pts were taken off of therapy prior to the first 3 month evaluation. The reason for withdrawal was pt refusal (2) and adverse events (2). The median event free survival was 2.6 months (95% CI:1.4–4.4 mos) with a median overall survival of 23.3 months. Toxicity information on 24/25 pts revealed 4 (17%) with grade 4 neutropenia with 1/4 febrile as well. The most common grade 3 toxicities were anemia (13%), dyspnea (13%), fatigue (8%) and neurologic toxicities consisting of somnolence, dizziness, depression and anxiety (21%). Peripheral sensory neuropathy was reported as gr 2 in 8% and gr 3 in 8%. However, 38% of pts were reported as experiencing gr 2 fatigue. There were no grade 5 toxicities. Conclusion: These phase II trial results in a pretreated pt population demonstrate that, despite an acceptable toxicity profile, thalidomide has only minimal efficacy in F- NHL and SLL.

Liposomal Amphotericin B IV (LIPO AB) Once Per Week Is Effective in the Prevention of Invasive Fungal Infections (IFI) in Patients (Pts) with Acute Leukemia: Preliminary Analysis of a Randomized Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1824-1824
Author(s):  
Gloria Mattiuzzi ◽  
Jorge Cortes ◽  
Deborah Blamble ◽  
Elihu Estey ◽  
Hagop Kantarjian
Keyword(s):  
Adverse Events ◽  
Randomized Trial ◽  
Fungal Infections ◽  
Performance Status ◽  
Study Drug ◽  
Disease Status ◽  
Myelogenous Leukemia ◽  
Remission Induction ◽  
Drug Discontinuation ◽  
Grade 3

Abstract Background: IFI remain an important cause of morbidity and mortality in pts with acute myelogenous leukemia or high risk myelodysplastic syndrome (AML/HR-MDS). We have previously shown that voriconazole (VORI) or LIPO AB 3 mg/kg/day TIW were effective prophylactic regimens in AML/HR-MDS. LIPO AB given once every week achieves tissue levels expected to prevent IFI, decreases the risk for infusion-related adverse events (IRE) and would simplify prophylaxis. Materials and Methods: We conducted a 3-arm randomized trial comparing LIPO AB, 3 mg/kg/d TIW (LIPO AB 3); versus LIPO AB 9 mg/kg/d, 1/week (LIPO AB 9); versus VORI 200 mg PO 2/day among pts with AML/MDS undergoing induction or salvage chemotherapy (CHEMO). Pts were stratified by age and disease status and randomized to receive any of the 3 regimens 24 hours after completion of CHEMO. Serum Galactomannan Index (GMI) was obtained 2/week while CT scan of chest (CT) was performed for persistent fever after 3 days of broad spectrum antibiotics. Proven and probable IFI were defined according to EORTC/MSG criteria. The results of the first 59 pts (of 150 planned) enrolled between Dec 06 -July 07 are presented. Results: Pts characteristics and response are shown in Table 1. All pts had Zubrod performance status ≤ 2 and most underwent remission induction chemo (90% in each group). No significant differences were observed on key baseline characteristics. Three of the 59 pts did not receive study drug (AMBI 9=2; VORI=1) and were excluded from efficacy and safety analysis. There were no proven IFI; 3 pts developed probable pulmonary Aspergillosis [GMI(+); CT (+), cultures (−) ], while 10 pts received additional empirical antifungal therapy (AFT) because of FUO [ 7 pts; GMI (−), CT (−), cultures (−)] or pneumonia [ 3 pts; GMI (−), cultures (−)]. None of these 10 pts developed proven/probable IFI. Two pts in each study arm developed reversible side effects that lead to drug discontinuation [AMBI 3: Grade 2 hyperbilirubinemia (1); Grade 3 infusion related events (1); AMBI 9: Grade 3 infusion related event (2); VORI: Grade 2 hyperbilirubinemia (1), visual hallucinations (1)]. Overall mortality was 5% (1 pt/arm). There were no IFI-related deaths. Conclusion: Intermittent LIPO AB (3 mg/kg/d TIW or 9 mg/kg/d, 1/week) and VORI 200 mg PO 2/day prophylaxis appear to be effective and well-tolerated regimens. Enrollment of additional pts is ongoing. Table 1 LIPO AB 3 (n=20) LIPO AB 9 (n=20) VORI (n=19) *p=ns; **p=0.061 Median age* (range) 60 (40–79) 60 (23–69) 58 (31–77) Pts in protected environment* (%) 80 65 79 Diabetes mellitus**, n(%) 1 (5) 1 (5) 5 (26) Median days on prophylaxis* (range) 17 (1–34) 14 (1–37) 17 (1–37) Efficacy and adverse events LIPO AB 3 (n=20) LIPO AB 9 (n=18) VORI (n=18) No IFI*, n(%) 14 (70) 14 (78) 15 (83) Proven/Probable IFI*, n(%) 2 (10) 1 (5) 0 Empiric AFT*, n(%) 4 (10) 3 (17) 3 (17) Adverse events*, n 4 4 3 All drug-related*, n(%) 2 (10) 2 (11) 2 (11)

European Post-Approval Safety Study (PASS) of Relapsed/Refractory Multiple Myeloma (RRMM): Safety, Including SPM, in a Large Cohort of Patients Treated with Lenalidomide, Thalidomide, and Bortezomib

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3331-3331
Author(s):  
Barbara Gamberi ◽  
Miguel Hernandez ◽  
Christian Berthou ◽  
Eleni Tholouli ◽  
Elena Zamagni ◽  
...  
Keyword(s):  
Adverse Events ◽  
Board Of Directors ◽  
Research Funding ◽  
Performance Status ◽  
Treatment Discontinuation ◽  
Second Primary ◽  
Advisory Committees ◽  
Grade 3 ◽  
Noninterventional Study ◽  
Dose Reductions

Abstract Background: EU PASS is an observational, noninterventional study designed to investigate the safety of lenalidomide (LEN) and other agents in the treatment of RRMM in a real-world setting. Aims:To assess the incidence of adverse events (AEs) of special interest, including neutropenia, thrombocytopenia, venous thromboembolism (VTE), peripheral neuropathy (PN), and second primary malignancies (SPMs) in RRMM patients (pts) treated with LEN and other antimyeloma therapies according to current clinical practice. Methods: Pts with RRMM who were commencing LEN treatment were enrolled at the investigator's discretion into a LEN cohort (LEN + dexamethasone, the approved combination for the treatment of RRMM); pts who received ≥ 1 prior therapy and were commencing a non-LEN-based therapy were enrolled into a background cohort (all other treatments, including novel agents). Thromboprophylaxis was per local standard practice. AEs were graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (version 3). SPMs were defined using Medical Dictionary for Regulatory Activities (MedDRA) terms under the category Neoplasms SOC. Following protocol amendment in 2011, assessments for SPMs were to be conducted up to 36 mos after treatment discontinuation. Results: As of June 2016, 3632 pts across 269 institutions in 17 European countries were included in the safety population. Of those, 59.2% received LEN (n = 2151), 32.7% received bortezomib (BORT; n = 1188), 3.8% received thalidomide (THAL; n = 137), and 4.3% received other therapies (n = 156). The majority of pts had discontinued from treatment (97.9%; n = 3556); of the 2.1% (n = 76) ongoing pts, 66 are treated with LEN, 6 with BORT, 0 with THAL, and 4 with other substances. Baseline characteristics were similar across the cohorts. Median age was 70 yrs (range, 25-95 yrs) and 54.0% were male. Of 2985 pts with available ECOG data, 2865 (96.0%) had good performance status (ECOG score 0-2), and the remaining 4.0% had an ECOG score of 3/4. The median number of prior therapies was 1 (range, 1-6) but was higher in the LEN cohort (2; range, 1-6) than in the BORT (1; range, 1-6) and THAL (1; range, 1-5) cohorts; the proportion of pts with only 1 prior treatment was also lower in the LEN cohort (44.3%), whereas BORT was 70.8% and THAL 56.2%. Overall, 50.7% of pts (n = 1842) had grade 3/4 AEs. Grade 3/4 neutropenia occurred in 17.1%, 3.5%, and 4.4% of pts in the LEN, BORT, and THAL cohorts, respectively, and grade 3/4 thrombocytopenia in 9.2%, 7.3%, and 3.6%. The incidence rate of SPM was 3.63 per 100 pt-yrs, with 3.18 per 100 pt-yrs in the LEN cohort, 5.23 per 100 pt-yrs in the BORT cohort, 2.73 per 100 pt-yrs in THAL, and 6.48 per 100 pt-yrs in others. AEs of interest of all grades are listed in Table 1. The median duration on study treatment was 6.6 mos (range, 0.1-81.6 mos) for LEN, 4.1 mos (range, 0-63.6 mos) for BORT, and 4.6 mos (range, 0.2-36.9 mos) for THAL. Treatment discontinuation rate due to AEs was similar in each cohort (22.1% in the LEN, 20.0% in the BORT, and 21.2% in the THAL cohorts). In the LEN cohort, dose reductions occurred in 38.1% of pts, with a median time to first dose reduction due to AEs of 12.4 weeks. Treatment-emergent adverse events leading to dose reductions were similar across cohorts, with 23.7% in the LEN cohort, 21.4% in the BORT cohort, and 17.5% in the THAL cohort. Conclusions: Results of this noninterventional study in RRMM show that AEs were similar across cohorts except for higher rates of neutropenia and lower rates of PN with LEN compared with THAL or BORT. Higher rates of neutropenia did not translate into increased febrile neutropenia. Infections, independent from neutrophil counts, occurred in all cohorts, but few pts developed serious infections such as pneumonia. VTEs as well as myocardial infarctions were low throughout all cohorts. The occurrence of SPMs was generally low and comparable between cohorts. LEN was generally well tolerated. Disclosures Tholouli: Johnson and Johnson: Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Celgene: Honoraria; MSD: Speakers Bureau; Giles: Speakers Bureau. Hájek:Janssen: Honoraria; Takeda: Consultancy; BMS: Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Research Funding. Minnema:Celgene: Consultancy; BMS: Consultancy; Amgen: Consultancy; Jansen Cilag: Consultancy. Dimopoulos:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genesis: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Frost Andersen:Celgene: Research Funding. Waage:Amgen: Speakers Bureau; Celgene: Consultancy, Honoraria; Novartis, Amgen, Celgene: Membership on an entity's Board of Directors or advisory committees. Crotty:BMS, Takeda, Novartis, Janssen, Roche: Honoraria. Kueenburg:Celgene International Sarl: Consultancy, Honoraria. Di Micco:Celgene: Employment. Bacon:Celgene: Employment, Equity Ownership.

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