Assisted Administration Of  Subcutaneous 5-Azacytidine  to The Patient's Home. Significant Reduction Of Indirect Costs Incurred By Care Recipients and Unpaid Caregivers Together With a Total Adhesion To The Treatment Schedule and Same Safety

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5587-5587
Author(s):  
Francesco Iuliano ◽  
Eleonora Iuliano ◽  
Alessia Perricelli ◽  
Angelo Pomillo ◽  
Maria Luci ◽  
...  
Keyword(s):  
Adverse Events ◽  
Injection Site Reaction ◽  
Indirect Costs ◽  
Median Number ◽  
Treatment Schedule ◽  
Hospital Inpatient ◽  
Adherence To Treatment ◽  
Care Recipients ◽  
Grade 3 ◽  
Rbc Transfusion

Abstract Background and aim Administration of azacitidine is planned in-patient daily, there is no experience of its administration to the patient's home. The aim of this work was to evaluate the feasibility of a program of home administration of azacitidine able to reducing the cost-of-illness, to increase adherence to treatment while maintaining the same safety of the therapy given in hospital. Material and methods Between Jan 2008 and Dec 2012, 22 consecutive  patients, (MDSs, n = 15; CMML, n = 4; AML, n = 3), were enrolled in the study. The pharmacoeconomic analysis included assessment of direct costs ( hospital inpatient, physician inpatient, physician outpatient, emergency department nursing home care, specialists’ and other health professionals’ care, diagnostic tests, prescription drugs and drug sundries, and medical supplies),indirect costs incurred by care recipients and unpaid caregivers, including time, productivity and travel cost. Results Azacitidine 75 mg/m2/day was administered as a subcutaneous injection for 7 consecutive days  every 4 weeks,  Median age of the patients was 71 years (range, 65–83). Median number of courses delivered to each patient was 9 (range, 3–31) Hematologic responses (CR/PR/mCR) were induced in 6 patients (27.0%)  Median number of treatment courses to achieve any response was 2 (range, 1–6) Adverse events were evaluated for the first 6 courses for all patients, for a total of 124 courses. Major adverse events were cytopenia and cytopenia-related infection. Grade 3 or higher neutropenia was 64.4%) but incidence of febrile episode requiring intravenous antibiotics was  8,4% slightly lower than reported from the pivotal clinical study. Grade 3 or higher non-hematologic toxicities were infrequent. Injection site reaction 0.4 and site pain 0% Median follow-up duration of surviving patients was 46.9 months (range, 11.8–55.5). Of the 14 patients  who were RBC transfusion dependent at baseline, 48.0% of these patients became RBC transfusion independent during the treatment period. Adherence to treatment was 100%. In our experience, despite the high percentage of elderly patients of whom 36% living in rural area, it was possible to give treatment to all patients with 100% adherence. There has been a reduction in direct medical costs due  to less use of hospitalization, a reduction of indirect costs by 63% due to the lower number of working days lost and a drastic reduction of travel costs, with the same efficacy and safety of administration. Disclosures: Off Label Use: drug administration at patient home instead of hospital.

scholarly journals Assisted Administration of Subcutaneous Rituximab to the Patient's Home. Significant Reduction of Indirect Costs Incurred By Care Recipients and Unpaid Caregivers Together with a Total Adherence to the Treatment Schedule and Same Safety

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5869-5869
Author(s):  
Francesco Iuliano ◽  
Eleonora Iuliano ◽  
Marco Rossi
Keyword(s):  
Home Care ◽  
Prescription Drugs ◽  
Conflicts Of Interest ◽  
Subcutaneous Administration ◽  
Indirect Costs ◽  
Nursing Home Care ◽  
Fixed Dose ◽  
Treatment Schedule ◽  
Hospital Inpatient ◽  
Care Recipients

Abstract Dec 2018, 7 consecutive patients, ( CLL n = 1; FL n = 3; DLBCL n= 1 AEA n=1,ITP n=1), were enrolled in the study. Median age of the patients was 68 years (range, 28-87). The pharmacoeconomic analysis included assessment of direct costs ( hospital inpatient, physician inpatient, physician outpatient, emergency department nursing home care, specialists' and other health professionals' care, diagnostic tests, prescription drugs and drug sundries, and medical supplies),indirect costs incurred by care recipients and unpaid caregivers, including time, productivity and travel cost. Results Rituximab subcutaneous formulation was administered at a fixed dose of 1400 mg with a frequency related to the type and the phase of the treated disease. Before starting MabThera subcutaneous injections, all patients received beforehand, a full dose of Rituximab by intravenous infusion. Premedication with an anti-pyretic an antihistaminic and prednisone , was given orally in the evening before and the morning of the subcutaneous administration the infusion was carried out by the staff of the home care unit together with a doctor. All the procedure was controlled by the hospital specialist through a smart-phone. Median age of the patients was 58 years (range, 32-83). Median number of courses delivered to each patient was 6 (range, 4- 12) .Adherence to treatment was 100%.No Infusion related adverse reactions have been observed. Conclusion In our experience, despite the high percentage of elderly patients of whom 36% living in rural area, it was possible to give treatment to all patients with high adherence and satisfaction. There has been a reduction in direct medical costs due to less use of hospitalization, a reduction of indirect costs by 70% due to the lower number of working days lost and a drastic reduction of travel costs, with the same safety of administration. Disclosures No relevant conflicts of interest to declare.

The efficacy and safety of anlotinib in refractory/recurrent/advanced pediatric solid tumors: A retrospective study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11556-11556
Author(s):  
Suying Lu ◽  
Ye Hong ◽  
Huimou Chen ◽  
Liuhong Wu ◽  
Jia Zhu ◽  
...  
Keyword(s):  
Adverse Events ◽  
Effective Treatment ◽  
Solid Tumors ◽  
Objective Response ◽  
Cancer Center ◽  
Treatment Schedule ◽  
Efficacy And Safety ◽  
Pediatric Solid Tumors ◽  
Hand Foot Syndrome ◽  
Grade 3

11556 Background: Refractory and recurrent advanced pediatric solid tumors are short of effective treatment and with a dismal outcome, thus an urgent need for novel and effective treatment. The aim of the study is to evaluate the efficacy and safety of anlotinib, a novel and oral multi-target receptor tyrosine kinase inhibitor, in refractory or recurrent advanced pediatric solid tumors. Methods: The retrospective, single-institutional, observed study was conducted in Sun Yat-sen University cancer center in China. Refractory, recurrent, or advanced pediatric solid tumors patients treated with anlotinib between 2018 to 2020 were evaluated. Results: Forty-one patients and thirty patients were enrolled in the study to evaluated efficacy and safety, respectively. The objective response ratio (ORR) was 12.2% (95%CI 1.7-22.7): complete response (n = 0) and partial response (n = 5) (Table). The disease control rate (DCR) was 65.9% (95%CI 50.7-81). The median progression-free survival (PFS) was 2.87 months (95%CI 0.86-4.88). According to anlotinib treatment schedule, all patients were divided into three groups: anlotinib monotherapy (A, n = 16), anlotinib combined with immune checkpoint inhibitor treatment (A + ICI, n = 6), anlotinib combined with salvage chemotherapy (A + SC, n = 19). The ORR, DCR and median PFS for three groups were 6.3% (95%CI 7.1-19.6), 56.3% (95%CI 28.9-83.6), 2.43months, 16.7% (95%CI 26.2-59.5), 66.7% (95%CI 12.5-120.9), 1.13months, 15.8% (95%CI 2.3-33.8), 73.7% (95%CI 51.9-95.5), 2.87months, respectively. There was no significantly difference between three groups in aforementioned response index. The incidence rates of any grade and grade 3-4 adverse events were 80% and 20%, respectively. Bleeding (20%), hand-foot syndrome (13.3%), and diarrhea (13.3%) were the most common adverse events. Grade 3-4 adverse events include hypertension, hand-foot syndrome, diarrhea, anemia, and thrombocytopenia. There was no adverse events-related death. Conclusions: For heavily pretreated pediatric solid tumors, anlotinib may be an effective treatment with tolerable adverse events. Further prospective randomized controlled clinical study is warranted.[Table: see text]

scholarly journals A phase I/II trial to treat massive Africanized honeybee (Apis mellifera) stings using the new apilic antivenom

2021 ◽  
Author(s):  
Alexandre Naime Barbosa ◽  
Rui Seabra Ferreira ◽  
Francilene Capel Tavares de Carvalho ◽  
Fabiana Schuelter-Trevisol ◽  
Mônica Bannwart Mendes ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Apis Mellifera ◽  
Adverse Events ◽  
Phase I ◽  
Adverse Reactions ◽  
Median Number ◽  
Treatment Schedule ◽  
Africanized Honeybee ◽  
Hospitalization Period ◽  
Safety Endpoint

ABSTRACTSafety, optimal minimum dose, and, preliminary effectiveness of a new generation Africanized honeybees (Apis mellifera) antivenom (AAV) were evaluated. A phase I/II, multicenter, non- randomized, single-arm clinical trial involving 20 participants showing multiple stings were studied. Participants have received either 2 to 10 vials of AAV based on the stings number together with a predefined adjuvant, symptomatic, and complementary treatment schedule. The primary safety endpoint was the presence of early adverse reactions within the first 24 hours after treatment. Preliminary efficacy through clinical evolution, including laboratory tests, was assessed at baseline and over the following four weeks. ELISA assays and mass spectrometry estimated the venom pharmacokinetics before, during, and after treatment. Twenty adult participants, 13 (65%) males, and 7 (35%) females, with a median age of 44 years and a mean body surface of 1.92 m2 (median = 1.93 m2) were recruited. The median number of stings was 52.5 ranging from 7 to more than 2,000. Envenoming severity was classified as 80% mild, 15% moderate, and 5% severe. According to the protocol, 16 (80%) participants received two AAV vials, 3 (15%) six vials, and one (5%) 10 vials. There was no discontinuation of the treatment due to acute adverse events and there were no late adverse reactions. Two patients showed mild adverse events with only transient itchy skin and erythroderma. All participants completed the infusion within two hours and there was no loss of follow-up after discharge. ELISA assays showed venom concentrations varying between 0.25 ng/mL and 1.479 ng/mL prior to treatment. Venom levels decreased in all cases during the hospitalization period. Surprisingly, in nine cases (45%), despite clinical recovery and without symptoms, the venom levels increased again during outpatient care 10 days after discharge. Mass spectrometry showed melittin in eight participants 30 days after the treatment. Considering the promising safety results of the investigational product for the treatment of massive Africanized honeybee attacks, added to efficacy in clinical improvement and immediate decrease in blood venom level, the AAV has shown to be safe for human use.Trial registrationUniversal Trial Number (UTN): U1111-1160-7011, Register Number: RBR-3fthf8 (http://www.ensaiosclinicos.gov.br/rg/RBR-3fthf8/).

scholarly journals The Outcomes of Nivolumab Fixed Dose 40 Mg Therapy in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-6
Author(s):  
Liudmila Fedorova ◽  
Kirill Lepik ◽  
Polina Kotselyabina ◽  
Elena Kondakova ◽  
Yuri Zalyalov ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Progression ◽  
Hodgkin Lymphoma ◽  
Median Number ◽  
Fixed Dose ◽  
Published Data ◽  
High Dose ◽  
Efficacy And Safety ◽  
Classical Hodgkin Lymphoma ◽  
Grade 3

Background Currently, the recommended dose of nivolumab for patients with relapsed or refractory classical Hodgkin lymphoma (r/r сHL) is 3 mg/kg. Nevertheless, published clinical cases indicate the possible efficacy of lower doses of nivolumab. Moreover, experimental studies provided the rationale for possible reduction of nivolumab dose in patients with solid tumors (Agrawal et al. 2016). The presented data creates prerequisites for studying the lower nivolumab doses efficacy and safety in the r/r cHL therapy. Patients and Methods This study included 42 patients (14 male/28 female) with r/r cHL who were treated with nivolumab 40 mg every 2 weeks. The median age of patients was 36 (22-53) years. The median number of prior therapy lines was 4 (2-7). Prior treatment contained high dose chemotherapy with ASCT in 9 pts (21%), brentuximab vedotin in 14 pts (33%) and allo-HSCT in 1 pt (2%). Four pts (9,5%) had the partial response (PR) and the remaining 38 pts (90,5%) had the disease progression (PD) at the moment of nivolumab initiation. B-symptoms were present in 23 pts (55%), ECOG status was grade 0-I in 25 pts (59,5%), grade II in 12 pts (29%), grade III in 4 pts (9,5%) and grade IV in 1 pt (2%). The primary endpoint was the overall response rate (ORR) determined by positron-emission tomography/computed tomography (PET/CT) using LYRIC criteria every 3 months. Key secondary endpoints included progression-free survival (PFS) and overall survival (OS). Adverse events (AE) were evaluated according to CTCAE 4.03. The patient group characteristics were evaluated using descriptive statistics methods, the survival analysis was performed using Kaplan-Meyer method (SPSS Statistics v.17). Results The median number of nivolumab cycles was 24 (2-38). The response was evaluated in 41 out of 42 pts. The ORR was 66%. The best response included complete response (CR) in 39%, PR in 27%, stable disease in 5%, PD in 2%, indeterminate response (IR) in 27% of pts. With a median follow-up of 27,5 mo (11,3-34,5) 41 pts (97,6%) were alive, the median OS was not reached. The 2-year PFS was 44,5% (95% CI, 28,2-59,6) The nivolumab therapy was discontinued in 39 pts (93%) due to scheduled discontinuation in 14 pts (33%), PD in 13 pts (31%), grade 3-4 AE in 2 pts (5%), change of therapy because of insufficient response in 6 pts (14%) and other reasons in 4 pts (10%). The progression of disease during nivolumab therapy was present in 14 (33%) pts and after nivolumab discontinuation in 6 (14%) pts. After disease progression 30 pts (71%) were retreated with nivolumab monotherapy or in combination with chemotherapy. The median time to additional therapy was 14,5 mo (4,2 -32,9). The adverse events of any severity were observed in 30 pts (71%). Grade 3 or higher AE were present in 4 pts (9,5%), including grade 3 arthralgia, grade 3 anemia, grade 4 pneumonia and pneumonitis, grade 4 increased level of alanine aminotransferase and grade 5 MDS in 1 pt. A significant reduction of PD1+CD3+ cell population of peripheral blood lymphocytes was observed after first nivolumab cycle (median 0.7% (0-1.7) versus 33% (15.7-80.1) before therapy initiation, p = 0.02, Wilcoxon signed-rank test). Conclusion Our study demonstrated the efficacy and safety of nivolumab 40 mg therapy. The presented results are comparable to previously published data of nivolumab 3 mg/kg therapy in patients with r/r cHL. Thus, this creates a basis for further direct comparative study of nivolumab efficacy in different doses Disclosures No relevant conflicts of interest to declare.

Optimal use of antihypertensive agents in management of bevacizumab-associated hypertension.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 614-614
Author(s):  
M. Suenaga ◽  
H. Imada ◽  
E. Nakamoto ◽  
S. Matsusaka ◽  
T. Watanabe ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adverse Events ◽  
Total Duration ◽  
Antihypertensive Agents ◽  
Median Number ◽  
Management Protocol ◽  
First Choice ◽  
History Of ◽  
Grade 3 ◽  
Number Of Treatment

614 Background: Hypertension (HT) is the most common toxicity associated with bevacizumab (BV). Angiotensin converting enzyme inhibitors, calcium channel blockers (CCB), beta-blockers or diuretics are frequently chosen to control BV-associated HT. However, optimal use of these antihypertensive (AHT) agents for each grade of HT remains to be determined. Furthermore, the AHT agent to be used must be carefully chosen to avoid increasing risk for BV-associated cardiovascular adverse events. Methods: Seventy-five consecutive patients with metastatic colorectal cancer who received first-line FOLFOX4 plus BV 5 mg/kg were included in the study. Treatment continued until progression of disease or unmanageable toxicity occurred. Blood pressure was measured prior to treatment in each cycle and graded using the NCI–CTC, version 3.0. The management protocol was as follows: 8-12 mg candesartan cilexetil (an angiotensin II receptor antagonist) as the first choice for grade 2 HT; 2.5 mg ≤ additional amlodipine besylate (a CCB) when grade 3 HT occurred; BV was discontinued if HT remained uncontrolled with use of both these agents. Stable blood pressure < 150/100mmHg during treatment was defined as manageable. Results: Twenty patients (26.7%) had a history of HT. Grades 2-3 HT developed in 53 patients (70.7%) and grade 3 in 24 (32%). Median number of treatment cycles until onset of grades 2 and 3 HT was 3 and 4.5, respectively. Comparing patients with a history of HT to those without, the incidence of grade 3 was greater in the former (85 vs. 12.7%, respectively), and the median number of treatment cycles until onset of grade 3 was shorter (4 vs. 12 cycles, respectively); blood pressure was considered manageable in both groups (90 vs. 91%, respectively), and no difference in total duration of chemotherapy was observed. No AHT approach-related severe adverse events were observed. Conclusions: Grade 3 HT was manageable during BV treatment, regardless of prior hypertensive history. However, to ensure improved survival, especially in patients with a history of HT, appropriate management is needed in BV-associated grade 3 HT. These data suggest that use of AHT agents is an effective and safe strategy in the management of BV-associated HT. No significant financial relationships to disclose.

Effect of lenalidomide (LEN) on biochemical responses and clinical benefit (CB) as a single agent in chemotherapy-naive castration-resistant prostate cancer (CRPC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 128-128 ◽  
Author(s):  
Chadi Nabhan ◽  
Anand Patel ◽  
Dana Villines ◽  
Kathy Tolzien ◽  
Susan K. Kelby ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Benefit ◽  
Single Agent ◽  
Complete Response ◽  
Median Number ◽  
Castration Resistant Prostate Cancer ◽  
Serious Adverse Events ◽  
Biochemical Responses ◽  
Grade 3 ◽  
Dose Reductions

128 Background: LEN has anti-angiogenesis and immunomodulatory properties making it ideal to investigate in CRPC. We report on a phase II study investigating LEN in chemotherapy-naïve CRPC patients (pts) Methods: Eligible pts received LEN at 25 mg daily on days 1 – 21 every 28-days until progression. Daily aspirin or coumadin were required. Responses were assessed every 2 cycles. Toxicity was assessed every cycle. Primary end point: The CB of LEN [Sum of complete response (CR), partial response (PR) and stable disease (SD)]. Secondary end points: Toxicity, time to radiographic and PSA progression (TTP and TTP-PSA), time to next treatment (TTNT), overall survival (OS), and LEN’s impact on quality of life (QOL). Results: 31 pts were enrolled; 27 response-evaluable (1 withdrew consent, 3 off per choice after adverse events). Median age is 74 (range 58-89) with 24 (77%) having Gleason ≥ 7 disease. Median PSA is 66 (2.1-918.6). Six pts (19%) had liver/lung involvement. Fourteen pts (51%) showed biochemical response with 4 (15%) having >50% PSA drop. TTP-PSA is 4 months (2-11). No radiographic responses seen but 17 pts had SD for a median of 4 months (2-16) (CB=55%). Median number of LEN cycles was 3 (2-15). With a median follow-up of 18 months (5-38), 17 patients (55%) remain alive; median OS of 18 months. Grade 3/4 hematologic toxicities were most common (neutropenia 41%, leukopenia 12%, anemia 9%, thrombocytopenia 9%). Other grade 3/4 toxicities: venothromboembolism, atrial fibrillation, and dehydration (6% each). Serious adverse events (SAEs) were witnessed in 10 pts (32%) with only 1 (3%, rash) definitely related to LEN. Others were not related or possibly related. Of 27 pts, 7 (26%) had a dose reduction and 2 (7%) required two dose reductions. Dose reductions occurred after cycle 3. QOL scales suggested no adverse impact. Median TTNT is 2 months (9 pts received chemotherapy, 10 pts went onto studies, 3 pts received hormonal therapies, 4 pts received radiation, 3 pts had no therapy yet, and 2 pts remain on LEN). Conclusions: LEN is active as monotherapy in CRPC. Biochemical responses are witnessed and clinical benefit is observed. Myelosuppression is the most common toxicity.

Real-life use of nivolumab and pembrolizumab in four adult university teaching hospitals in Québec, Canada.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14125-e14125 ◽  
Author(s):  
Nathalie Letarte ◽  
Layal El Raichani ◽  
Chantal Guevremont ◽  
Nathalie Marcotte ◽  
Ghislain Berard ◽  
...  
Keyword(s):  
General Population ◽  
Adverse Events ◽  
Real Life ◽  
Median Number ◽  
University Teaching ◽  
Teaching Hospitals ◽  
Grade 3 ◽  
Nsclc Patients ◽  
University Teaching Hospitals

e14125 Background: Nivolumab and pembrolizumab, two anti-PD1 agents, were approved and funded in Québec since 2016 for non small cell lung cancer (NSCLC), renal cell carcinoma (RCC) and melanoma. The objectives were to describe and assess the “real-life” use, efficacy and security of nivolumab and pembrolizumab in NSCLC, RCC and melanoma in the general population. Methods: Medical records of every patient who received nivolumab or pembrolizumab between January 1st 2011 and October 31st 2017 were reviewed retrospectively. Data analysis cut-off was Dec 31st 2017. Results: In total, 532 patients received at least one dose of anti-PD1 during the study period. Median number of doses received varied for each indication (medians varied from 4 to 9.5). Adverse events were pooled together by drug. 47.7 % of patients receiving pembrolizumab suffered from any grade immune-related adverse event (IRAE), most of them of grade 1 or 2. 12.2 % of patients reported grade 3-4 IRAE. Most of the patients reported only one type of IRAE. For nivolumab, 44.6% of patients presented with any IRAE, including 8.3% of grade 3-4. Dermatologic IRAE were more frequent in the melanoma patients whereas gastrointestinal and pulmonary IRAE were more frequent in NSCLC patients. Treatment discontinuation due to adverse events varied from 6 to18% depending on indication. Conclusions: Nivolumab and pembrolizumab seemed less effective and caused more IRAE in “real-life” population than in the pivotal clinical trials. Caution and regular follow-up are warranted when using these drugs in general population. Longer follow-up is needed.[Table: see text]

Weekly 20/56 mg/m² carfilzomib, lenalidomide, and dexamethasone until progression in early relapsed refractory multiple myeloma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8041-8041
Author(s):  
Cecile Gruchet ◽  
Valentine Richez ◽  
Stephanie Guidez ◽  
Guillemette Fouquet ◽  
Isabelle Azais ◽  
...  
Keyword(s):  
Adverse Events ◽  
Safety Profile ◽  
Prolonged Exposure ◽  
Safety Concern ◽  
Median Number ◽  
Continuous Exposure ◽  
Similar Data ◽  
Duration Of Treatment ◽  
Safety Issues ◽  
Grade 3

8041 Background: Triplet-based Carfilzomib (K), Lenalidomide and Dexamethasone combination (KRd) has led to approval in early RRMM based on ASPIRE International phase 3 study. However, K was used on a twice a week basis at 27mg/m2 and limited to 18 months exposure. We have reported already that KRd on a weekly basis at 56 mg/m2 was active similar to ASPIRE KRd and safe. We report herein the long-term exposure data on KRd weekly given until progression. We aimed to evaluate the efficacy of KRd given on a prolong duration beyond 18months, and to validate the safety profile of continuous exposure to K. Methods: 28 patients were prospectively recruited. Carfilzomib 20/56mg/m2 was administered on days 1,8,15, Lenalidomide 25mg/day was given 21/28 days and Dexamethasone was administered weekly on 28 days cycles until progression. Results: With a median follow-up at start of KRd of 30 months, 50% of patients relapsed and 39% died. 24/28 patients received 1 prior line of treatment. 8/28 patients are still on treatment with duration > 24 month and 6/28 with duration > 30 months. The median number of cycles was 15. ORR and CBR was 85.7% and 89.3%, whom 46% ≥ CR ; with a median DOR of 13 months and 43% having more than 18 months. 6 patients had negative MRD at 10-6 and normalized PET CT. Median of OS is not reached, and the 30 month-expected OS from the start of KRd was 56%. The median PFS and EFS was at 29 months, and the 30 month-expected PFS and EFS was 45%. PFS and EFS being superimposable speaks to that there was no safety concern related to prolonged exposure to K. Only 4 patients stopped KRd for safety issues. Hematologic and non-hematologic adverse events ≥ grade 3 were reported in 16/28 and 10/28 patients. Adverse events ≥ grade 3 seen in ≥10% of patients were neutropenia, thrombocytopenia, vomiting and pyrexia. Of note, 5 patients (18%) were ≥ 65 years old and showed similar data compared to the cohort. Conclusions: KRd weekly is effective and safe to early in RRMM patients, provides improved safety profile to patients allowing treating patients until progression. Further studies are warranted to confirm this data on a larger early RRMM population and validate the concept of long duration of treatment using Carfilzomib combination.

scholarly journals Carfilzomib Weekly 20/56mg/m², Lenalidomide and Dexamethasone for Early Relapsed Refractory Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3276-3276
Author(s):  
Valentine Richez ◽  
Cécile Gruchet ◽  
Stephanie Guidez ◽  
Guillemette Fouquet ◽  
Isabelle Azais ◽  
...  
Keyword(s):  
Adverse Events ◽  
Board Of Directors ◽  
Dose Intensity ◽  
Standard Of Care ◽  
Median Number ◽  
Advisory Committees ◽  
Safety Issues ◽  
Dose Concentration ◽  
Grade 3 ◽  
Dose Dense

Abstract Background. Triplet-based lenalidomide plus dexamethasone combinations have become the new standard of care for early RRMM, including with carfilzomib (KRd). In Aspire phase 3 trial for registration, carfilzomib was given on a dose dense twice a week but not dose intense 20/27 mg/m² dose concentration. In parallel, several studies seem to demonstrate that dose intensity, with increased dose concentration of carfilzomib, could compensate for a less dose dense regimen with carfilzomib weekly. We hypothesized that weekly carfilzomib regimen of KRd will improve time on treatment and quality of life and thus PFS and possibly OS. We aimed to evaluate the efficacy and toxicity of carfilzomib weekly plus lenalidomide/dexamethasone regimen in early RRMM. Methods. 28 patients were prospectively recruited. Carfilzomib was administered as a 30-minute infusion on days 1,8,15 (at 20mg/m2 on day 1 of cycle 1; then 56mg/m2 thereafter). Lenalidomide (25mg/days) was given 21/28. Dexamethasone was administered weekly. Results. With a median follow-up of 25 months, 42% relapsed and 17% died. Importantly, 16/28 (57%) are still on treatment. The median number of cycles was 18, with 32% of patients treated more than 20 cycles. Only 4 patients stopped weekly KRd for safety issues. ORR and CBR was 85.7% and 89.3%, whom 43% ≥CR; with a median DOR of 13 months and 43% having more than 18 months. 7 patients had negative MRD at 10-5 and normalized PET CT. The projected PFS, EFS and OS at 30 months were 56%, 43% and 82%, respectively. Hematologic and non-hematologic adverse events ≥ grade 3 were reported in 57% and 36%, respectively. Adverse events ≥ grade 3 seen in ≥10% of patients were neutropenia, thrombocytopenia, vomiting and pyrexia. Conclusion. KRd weekly at 20/56mg/m2 is effective and safe to early RRMM patients, provides improved safety profile and QOL to patients allowing treating patients until progression. Further studies are warranted to confirm this data on a larger early RRMM population and validate the ability to use dose intensity to improve the dose density approach using carfilzomib combination. Disclosures Leleu: BMS: 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; Abbvie: 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; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Obinutuzumab (GA101) in Combination with Pixantrone for the Treatment of Patients with Relapsed Aggressive B-Cell Lymphoma:Â a Phase II Trial (GOAL)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1678-1678 ◽  
Author(s):  
Georg Hess ◽  
Andreas Hüttmann ◽  
Julia Meissner ◽  
Reinhard Marks ◽  
Martin Dreyling ◽  
...  
Keyword(s):  
Adverse Events ◽  
B Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Median Number ◽  
Phase Iii ◽  
Advisory Committees ◽  
Phase Iii Trial ◽  
Grade 3 ◽  
One Year

Abstract Background: A substantial proportion of patients fail first line treatment of diffuse large B-cell lymphoma. Currently available salvage therapies are often ineffective and cannot be tolerated, especially for elderly patients. Thus, probably less than 25% of patients achieve a long lasting remission. Regimens like gemcitabine/oxaliplatin, or bendamustin, both in combination with rituximab are available for elderly or after failure of HDT, however induce only short lived responses. Obinutuzumab (GA101) is a type II anti-CD20 antibody, with preclinical evidence of superiority over rituximab in xenograft models of MCL and DLBCL. Recently a large phase III trial failed to show a benefit in patients with untreated DLBCL, although a subset analysis showed a potential benefit in a subset GCB DLBCL of patients, its value in relapsed disease is not yet finally determined. Although desirable, cumulative dose-related, progressive cardiotoxicity eliminates anthracyclines from relapse treatments. With pixantrone, a drug related to anthracyclines, a re-exposition against this drug class has been shown to be feasible, a best EOT-ORR of 37% (20% CR/CRu) was observed in a phase III trial. We thus initiated a trial combining both agents for the first time. The trial has opened in Q3/2015 and recruitment of 70 patients is completed as of 7/2018. Primary endpoint is the ORR, secondary endpoints being safety, PFS and OS. We report about available data after enrollment of the last patient. Methods: this is a multicenter, national, prospective trial. Main inclusion criteria: histologically proven DLBCL, FL grade IIIb or transformed iNHL (20% Quorum), no curative option available, relapsed and measurable disease, ECOG < 3, sufficient BM reserve, no severe concomitant diseases and given informed consent. There was no upper limit of prior treatment lines. Treatment consisted of up to 6 cycles of pixantrone 50mg/m² day 1, 8 and 15 of each cycle, obinutuzumab 1000 mg flat dose day 1, 8 and 15 of cycle one and day 1 of each subsequent cycle. Interim staging was scheduled after 3 cycles. Results: Basic data are available of 67 patients, all were caucasian, 37 were female the other 30 male and median age was 75 years. Most of the patients suffered from DLBCL (49 pts, 68%), 68% had advanced stage at diagnosis and the median secondary IPI was 3. Data collection is ongoing, until now data of 32 patients are fully available and updated results will be presented. Median number of prior therapies was 2 (1 to 6). Treatment seemed to be well tolerated, median number of cycles applied was 3, pre-mature stop of treatment was primarily based on progression. Response evaluation: at this time 13/32 (40.6%) evaluable patients responded with 5 patients achieving CR/CRu (15.6%) and 8 a PR. One year after initiation of treatment 54% of patients remained alive. Median follow up is 8.2 months. Median PFS and OS is 82 day and not reached, 1 year PFS and OS are 37% and 54%, respectively, no patient experienced relapse if the patient remained free from relapse at one year. Observed toxicity was predominantly hematologic. The following hematologic grade 3/4 adverse events were observed: leukopenia (9.4%) neutropenia (75%), thrombocytopenia (12.5%). The febrile neutropenia rate was 6.3%. Non-hematologic grade 3/4 adverse events were very rare, no single side effect was observed with a frequency of 5% or more. Summary: the combination of Obinutuzumab and Pixantrone is feasible and safe. Early response rates are interesting. Importantly, although some patients experience progress early, a promising proportion shows long lasting remissions. Molecular analyses are ongoing, as well as a detailed analysis on the impact of factors such as of number of prior treatments, status at inclusion. Figure. Figure. Disclosures Hess: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CTI: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Other: travel expenses, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Hüttmann:Celgene: Other: Travel expenses; Roche: Other: Travel expenses. Marks:BMS: Honoraria; Merck: Honoraria; Servier: Honoraria. Dreyling:Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Mundipharma: Consultancy, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Acerta: Consultancy; Sandoz: Consultancy. Keller:Takeda: Consultancy, Research Funding; MSD: Consultancy; Janssen-Cilag: Consultancy, Equity Ownership; Roche: Consultancy; BMS: Consultancy; Celgene: Research Funding. Ernst:Novartis: Research Funding. Viardot:Roche: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Amgen: Consultancy; Gilead Kite: Consultancy, Honoraria. Lenz:Novartis: Research Funding; Bayer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel, Accomodations, Expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, Accomodations, Expenses, Research Funding, Speakers Bureau; Celgene Corp.: Consultancy, Honoraria, Other: Travel, Accomodations, Expenses, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria.

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