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 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.

Preliminary results of the phase 2 study of zanubrutinib in patients with previously treated B-cell malignancies intolerant to ibrutinib and/or acalabrutinib.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19506-e19506
Author(s):  
Mazyar Shadman ◽  
Jeff Porter Sharman ◽  
Moshe Y. Levy ◽  
Ryan Porter ◽  
Syed Farhan Zafar ◽  
...  
Keyword(s):  
B Cell ◽  
Kinase Inhibitors ◽  
Median Number ◽  
Additional Treatment ◽  
Lymphocytic Leukemia ◽  
Continuous Treatment ◽  
Duration Of Treatment ◽  
B Cell Malignancies ◽  
Preliminary Results ◽  
Grade 3

e19506 Background: Many patients (pts) with B-cell malignancies require continuous treatment with Bruton tyrosine kinase inhibitors (BTKi). Adverse events (AEs) are a common reason for ibrutinib (ibr) or acalabrutinib (acala) discontinuation. Early data from BGB-3111-215 showed zanubrutinib (zanu) was well tolerated in pts with B-cell malignancies intolerant to ibr or acala. We report preliminary results with a median follow-up of 4.2 mo. Methods: Pts meeting protocol criteria for intolerance to ibr, acala or both (without documented progressive disease) were given zanu monotherapy (160 mg twice daily or 320 mg once daily). Recurrence of AEs that led to intolerance of prior BTKi and additional safety measures were assessed based on the Common Terminology Criteria for AEs v5.0. Investigators determined responses using disease status at study entry as baseline. Results: As of November 1, 2020 (cutoff), 44 pts (n=34 chronic lymphocytic leukemia/small lymphocytic lymphoma, n=6 Waldenström macroglobulinemia, n=2 mantle cell lymphoma, n=2 marginal zone lymphoma) were enrolled, received ≥1 dose of zanu, and analyzed for safety. Median age was 70.5 y (range, 49-91); median duration of treatment was 4.2 mo (range, 0.1-12.6). Median number of prior regimens was 2 (range, 1-12). Regarding prior BTKi, 39 pts received ibr only, 4 received ibr and acala, and 1 received acala only. The median number of ibr- or acala-intolerant AEs per pt was 2 (range, 1-5). 83% of ibr and 78% of acala intolerant events did not reccur on zanu; Table. At data cutoff, 43 pts remained on treatment; 1 withdrew consent due to zanu-unrelated grade 3 syncope. Overall, 34 pts (77.3%) reported any AE; most commonly reported AEs were myalgia (n=9; 20.5%), contusion (n=8; 18.2%), dizziness (n=7; 15.9%), fatigue (n=7; 15.9%), and cough (n=5; 11.4%). Grade ≥3 AEs were reported in 6 pts (13.6%), serious AEs in 1 pt (2.3%, febrile neutropenia and salmonella infection), AEs requiring dose interruptions in 6 pts (13.6%), and AEs leading to dose reduction in 2 pts (4.5%). No AEs led to zanu discontinuation. No deaths were reported. All efficacy evaluable pts (26/26 [100%]) maintained (10 [38.5%]) or achieved deepening (16 [61.5%]) of their response. Conclusions: Zanu provides an additional treatment option after intolerance to other BTKi, demonstrating tolerability and sustained or improved efficacy. Updated results will be presented. Recurrence and Severity Change of AEs Leading to Ibr or Acala Intolerance. Clinical trial information: NCT04116437. [Table: see text]

scholarly journals Sorafenib treatment by Child–Pugh score in Latin American patients with hepatocellular carcinoma

2020 ◽  
Vol 16 (31) ◽  
pp. 2511-2520
Author(s):  
Laura L de Guevara ◽  
Lucy Dagher ◽  
Vanessa MV Arruda ◽  
Keiko Nakajima ◽  
Masatoshi Kudo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Latin American ◽  
Treatment Option ◽  
Real World ◽  
Safety Profile ◽  
Treatment Duration ◽  
Sorafenib Treatment ◽  
Safety And Efficacy ◽  
Grade 3

Aim: To evaluate sorafenib treatment in Latin American patients with unresectable hepatocellular carcinoma in the real-world GIDEON study. Patients & methods: Sorafenib administration, safety and efficacy were analyzed by Child–Pugh status. Results: Of 90 evaluable patients (37% Child–Pugh A, 46% Child–Pugh B and 3% Child–Pugh C at study entry), 97% started sorafenib at 800 mg/day. Patients with Child–Pugh B7 had the longest median treatment duration of sorafenib (33.1 weeks). Sorafenib-related adverse events occurred in 58% of patients with Child–Pugh A (21% grade 3/4) and 46% with Child–Pugh B (7% grade 3/4). Conclusion: Sorafenib had a similar safety profile across patients with Child–Pugh A and B and is a treatment option for both groups.

An Open-Label Phase I Pharmacokinetic Study of [14c] Bendamustine in Patients with Relapsed or Refractory Malignancy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2476-2476 ◽  
Author(s):  
Anne-Charlotte Dubbelman ◽  
Hilde Rosing ◽  
Mona Darwish ◽  
Denise D'Andrea ◽  
Mary Bond ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Safety Profile ◽  
Half Life ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Open Label ◽  
Open Label Phase ◽  
Grade 3 ◽  
Refractory Malignancy

Abstract Abstract 2476 Background: Bendamustine is a unique alkylating agent which combines a nitrogen mustard moiety of mechlorethamine with a benzimidazole. This study was conducted to characterize the distribution, metabolism, and elimination of [14C] bendamustine and its metabolites (M3, M4, and dihydroxy bendamustine [HP2]) and to assess the roles of renal and hepatic pathways in the drug's metabolism and excretion. A secondary objective was to further characterize the safety profile of single-agent bendamustine. Methods: This open-label, phase I study enrolled 6 patients, age ≥18 years, with confirmed relapsed or refractory malignancy. The study was divided into 2 assessment periods: period A, during which the mass balance and pharmacokinetics of [14C] bendamustine were investigated, and period B, an extended-use period of up to 6 cycles with non-labeled bendamustine, during which safety continued to be assessed. Patients received intravenous (IV) bendamustine (120 mg/m2), containing 80–95 μCi of [14C] bendamustine, on day 1 of cycle 1 and non-labeled IV bendamustine (120 mg/m2) on day 2 of cycle 1 (period A). Pharmacokinetic parameters of bendamustine and metabolites M3, M4, and HP2 were calculated through plasma and urine concentrations, which were determined through 24 hours following administration of bendamustine on day 1. Total radioactivity (TRA) levels were measured in plasma, urine, and feces collected prior to drug administration and at time points through 168 hours after patients received [14C] bendamustine. Collection of excreta could continue (after the 7-day period) on an outpatient basis: if radiolabeled bendamustine ≥1% of dose was measurable in the 144- to 168-hour urine or feces collection, collection continued until the recovery in each 24-hour urine or feces collection was <1% of dose. Results: Six patients (3 males; 3 females) with a median age of 66 (48–75) years were enrolled and completed the pharmacokinetic portion of the study. For bendamustine, the decline from peak plasma concentration was characterized by an initial rapid distribution phase, followed by a somewhat slower intermediate phase. The pharmacologically relevant half-life (t½) was approximately 40 minutes. The plasma concentrations of M3, M4, and HP2 were very low relative to the bendamustine concentrations. Of the TRA dose administered, approximately half of the dose was recovered in the urine and approximately a quarter of the dose was recovered in the feces. Less than 5% of TRA dose was recovered in the urine as unchanged bendamustine. Mean recovery of TRA in excreta was approximately 76% of the radiochemical dose. Total recovery was incomplete due to continued slow excretion of TRA at the end of the collection period. The sustained levels of radioactivity in the plasma as compared with plasma concentrations of bendamustine suggest that, despite the rapid clearance of bendamustine, 1 or more longer-lived [14C] bendamustine-derived materials remain in the plasma. These longer-lived materials likely include by-products of alkylation. As previously noted, bendamustine volume of distribution was small (Vss∼20 L). The steady-state volume of distribution for TRA was ∼50 L. These results confirm previous data and provide evidence that neither bendamustine nor TRA are extensively distributed into the tissues. All 6 patients withdrew prior to completion of period B due to disease progression (n = 4), an adverse event (n = 1), or refusal to continue treatment (n=1). Bendamustine was well tolerated when administered at a dosage of 120 mg/m2 for 2 to 3 cycles. The most frequent treatment-related adverse events were fatigue (50%) and vomiting (50%). A grade 3/4 absolute lymphocyte count decrease occurred in all patients at some point during the study. There were no other grade 3/4 hematologic adverse events. Conclusions: Bendamustine was extensively metabolized via multiple metabolic pathways, with subsequent excretion in both urine and feces. Bendamustine accumulation is not anticipated in cancer patients with renal or hepatic impairment due to the dose administration schedule and short intermediate half-life. Adverse events and hematologic changes were consistent with the known safety profile of bendamustine. This research was sponsored by and conducted by Cephalon, Inc., Frazer, PA. Disclosures: Darwish: Cephalon, Inc.: Employment. D'Andrea:Cephalon, Inc.: Employment. Bond:Cephalon, Inc.: Employment. Hellriegel:Cephalon, Inc.: Employment.

Long-Term Exposure to Pomalidomide-Dexamethasone in Pts with Refractory Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3466-3466
Author(s):  
Brigitte Pegourie ◽  
Marie Odile Petillon ◽  
Lionel Karlin ◽  
Denis Caillot ◽  
Murielle Roussel ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Prolonged Exposure ◽  
Safety Management ◽  
Alkylating Agents ◽  
Dose Intensity ◽  
Median Number ◽  
Duration Of Treatment ◽  
Multicentre Phase ◽  
Combining Data ◽  
One Year

Abstract Background. The IFM2009-02 study was launched in 2009, and randomized 84 patients (pts) with pomalidomide (oral 4 mg daily) and dexamethasone (oral 40 mg weekly) given either 21 days out of 28 or continuous. Whilst the overall median PFS was 4.6 months - this end stage very advanced RRMM population, we observed that 40% of the patients had a prolonged PFS and subsequently OS in the trial. We sought to analyze the characteristics of 58 pts that had more than 3 months of pomalidomide to study the effect of long exposure to Pomalidomide. Method. IFM 2009-02 was a multicentre phase 2 study of pts with RRMM who had at best a stable disease with the last course of bortezomib and of lenalidomide, or who were refractory to bortezomib and lenalidomide (IMWG). This analysis was performed on the ITT population combining data from the 2 study arms. We have analyzed the characteristics of pts according to duration of treatment with pomalidomide and dexamethasone 3 months to one year (<1 year) or more than one year (≥1 year). Results. 60% and 40% of pts were exposed to pomalidomide for <1 year and ≥1 year, respectively. The ORR for the <1 year group was 43%, the median PFS 4.6 months (CI95% 4;6) with only 6% at 12 months, and the median OS 15 months (4;6) and 65% at 12 months, 40% at 18 months. For the ≥1 year group, the response rate and survival were strikingly different, ORR at 83%, PFS 20.7 months, OS not reached (CI95% 40;-) and 100% at 12 months, 91% at 18 months. Of the pts in the <1 year, 87% have died versus 35% in the ≥1 year group. Of note, death of most pts occurred during the follow up period post pomalidomide therapy , however in a far greater extent for the <1 year group, 96% versus 67%, that could suggest it was more difficult to salvage these pts post pomalidomide. We next sought to identify the characteristics of the 2 groups. Interestingly, the median number of prior lines was similar across groups, 5 (range 1-10), with 89% and 79% of the pts exposed to more than 3 lines and 17% and 22% exposed to more than 6 lines, for the <1 year and ≥1 year groups, respectively. 40% and 48% of pts had Bortezomib as last line, 29% and 43% Lenalidomide, 43% and 26% and alkylating agent. Similarly, 80% and 74% of pts were refractory to Bortezomib, 89% versus 87% to Lenalidomide, 65% versus 75% to alkylating agents, 74% and 87% to the last line of therapy, respectively. 74% and 70% were double refractory (Bortezomib and Lenalidomide) and 60% and 70% were triple refractory (double +last line), respectively. The time from diagnosis to IFM 2009-02 study entry was also similar between cohorts, 5.8 and 6.5 years for <1 year and ≥1 year groups; however with 6% versus 26% of pts, entering the study in less than 3 years since diagnosis. There was no difference in terms of patients characteristics between groups, either patients-based such as gender, age, weight, or myeloma-based characteristics. However, serum beta 2m level was higher at diagnosis in the <1 year compared to the ≥1 year, 54% versus 35%, with a slightly more adverse cytogenetic profile 35% versus 12%, with the limitation that this was not available for all the patients. Presence of plasmacytoma/EMD was also greater in the former group, 20% versus 4%, respectively. It seems that the <1 year had more intrinsic adverse features of the tumor cells compared to the ≥1 year group. There was no clear difference in terms of safety management of pomalidomide and/or dexamethasone, with respect to the daily dose intensity of Pomalidomide (median, 3.0 and 2.9 mg/day), and the relative dose intensity of pomalidomide that was 89% and 84%, respectively; similar to the rate of dose reduction and dose interruption. Conclusion. Pomalidomide and dexamethasone is effective and well tolerated in these heavily pre-treated MM pts refractory to Bortezomib and Lenalidomide, with approximately 40% of the patients having a prolonged exposure to treatment, which translated into a significantly prolonged OS. Our study suggests that patients with more intrinsic adverse features of Myeloma tumor cells could not have prolonged exposure to pomalidomide as they progressed within a year from start of pomalidomide. Future studies should examine optimizing pomalidomide therapy in those patients, such as using multidrug pomalidomide-based combined regimens to prolong exposure to pomalidomide and improve the survival of these patients. Disclosures Karlin: Janssen: Honoraria; celgene: Consultancy, Honoraria; Sandoz: Consultancy. Stoppa:Celgene Jansen: Honoraria.

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]

Subcutaneous alemtuzumab in patients with refractory/relapsed B-CLL after a fludarabine-based regimen

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6600-6600
Author(s):  
R. Bezares ◽  
G. Stemmelin ◽  
D. Argentieri ◽  
E. Lanari ◽  
E. Guy-Garay ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Residual Disease ◽  
Single Agent ◽  
Complete Response ◽  
Median Number ◽  
Duration Of Treatment ◽  
Barr Virus ◽  
Epstein Barr ◽  
Grade 3 ◽  
Cmv Disease

6600 Background: Alemtuzumab is the only immunotherapy that is effective as a single agent in patients with B-CLL who are refractory to, or who have relapsed after, fludarabine therapy. The optimized schedule for alemtuzumab that achieves maximal efficacy with manageable toxicity is still being explored. We report the first interim analysis of a new, less intensive schedule of alemtuzumab SC to patients with refractory/relapsed B-CLL. Methods: Alemtuzumab was dose escalated from 10 to 20 mg during the first week, 30 mg bid during the second and third weeks, and 30 mg once weekly during weeks 4, 6, 8, 10, 12, 16, 20, 24, 28, 34, and 40. Antiviral prophylaxis included TMP/SMX bid 3 times a week and acyclovir 200 mg tid. Results: Patients (N = 36) with refractory (19%) or relapsed (81%) B-CLL had a median age of 67 years (range, 43–86 years), 28 were male, 61%/39% had Binet stage B/C disease, and 2 had B-cell prolymphocytic transformation. The median number of prior therapies was 1 (range, 1–4). The median duration of treatment was 7 weeks (range, 2–24 weeks), with a median cumulative alemtuzumab dose of 412 mg (range, 150–1,080 mg). Thirty-two patients were evaluable for response. The overall response rate of 93%: complete response (CR), 34%; unconfirmed CR, 6%; partial response (PR), 53%. Two patients (7%) did not respond to therapy. Of the 7 refractory patients, 5 had a PR, 1 did not respond, and 1 was not yet evaluable. Median overall survival was 10 months, which correlated with response and pretreatment status. Minimal residual disease (MRD) was measured by flow cytometry in 5 patients who achieved a CR: 3 patients had <0.5% of CD5/CD19/CD23+ cells, 1 patient had <5% of CLL cells, and 1 patient had <10% CLL cells. According to WHO toxicity criteria, 5 patients experienced grade 3/4 infection; 2 patients had grade 3 granulocytopenia/thrombocytopenia; 1 patient had cytomegalovirus (CMV) reactivation without CMV disease; and 1 patient developed Epstein-Barr Virus with prolonged bone marrow hypoplasia. Conclusions: Results of this interim analysis suggest that a less intense regimen of alemtuzumab is feasible, effective, and safe for patients with refractory/relapse B-CLL after fludarabine therapy. No significant financial relationships to disclose.

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