scholarly journals The Efficacy and Safety Profile of Ixazomib-Based Regimens in Patients with Relapsed/Refractory Multiple Myeloma in Routine Clinical Practice: Real World Data from a Multi-Center Study in China

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5592-5592
Author(s):  
Jing Li ◽  
Li Bao ◽  
Zhong-jun Xia ◽  
Kaiyang Ding ◽  
Bingzong Li ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Adverse Events ◽  
Real Life ◽  
Routine Clinical Practice ◽  
Efficacy And Safety ◽  
Grade 3 ◽  
Ecog Ps ◽  
Refractory Diseases

J Li, L Bao, ZJ Xia and KY Ding contributed equally to this study. Background: Based on the promising results shown in the phase 3 trial (TOURMALINE-MM1, NCT01564537) and the China Continuation Study of MM1, the oral proteasome inhibitor (PI) ixazomib (ixa) was approved in China in April of 2018, in combination with lenalidomide (len) and dexamethasone (dex) (IRd), for patients (pts) with relapsed/refractory multiple myeloma (RRMM). Data on the efficacy and safety of ixa-based therapy in Chinese pts with MM in real-life practice is rather limited. A large national, multi-center, real-world study involving 14 centers from different areas of China was performed to investigate the current status of ixa usage in China and to evaluate the efficacy and safety in routine clinical practice. A total of 246 ixa-treated MM pts was enrolled, with 163 (66.3%) RRMM, 60 (24.4%) newly diagnosed MM and 23 (9.4%) pts received ixa as maintenance. Herein, we reported the data of RRMM in this study. Methods: Medical records, including demographics, disease characteristics, treatment regimen and duration, response rate, adverse events (AEs) and survival, of ixa-treated (at least one cycle completed with response evaluation result) RRMM pts were analyzed. Results: A total of 149 evaluable pts (out of 163 RRMM pts) treated from April 2018, to July 2019 were included in analysis. Baseline features and prior treatment are summarized in Table 1. Patients were categorized into MM1 trial-eligible/-ineligible groups according to the inclusion and exclusion criteria of MM1 study. Median age was 62 years (range 33 - 87) with 52 (34.9%) ≥65 years. Most pts (75.2%) had ISS stage II-III disease. High-risk cytogenetic abnormalities (including del 17p, t (4;14), and/or t (14;16)) were detected in 19 patients (21.1%, among 90 patients with FISH results). Fifty-two (34.9%) pts had a ECOG PS ≥2. Overall, ixa-based regimens were used as the 2nd/3rd/4th/≥5th-line therapy in 29.7%, 33.1%, 16.2% and 17.4% of the pts, respectively. Prior treatment included bortezomib (91.9%), len (52.0%) and thalidomide (58.8%). More than half pts (54.7%) were refractory to previous bortezomib treatment, and 32.2% pts were len-refractory. MM-1 trial-ineligible pts had more advanced ISS stage, higher ECOG PS, more severe anemia, more lines of prior therapy and more refractory diseases. Treatment, outcome and survival were listed in Table 2. Ixa-based regimens included IRd in 70 (47.0%) patients, ixa-dex (Id) in 31 (20.8%) patients and Id plus chemotherapeutics/other agents (44, 29.5%; including cyclophosphamide in 14 pts, thalidomide in 12 pts, adriamycin in 6 pts, melphalan in 5 pts and daratumumab in 3 pts) in 20 (33.3%). (Table 2). One patient received stem cell transplantation (SCT) during follow-up. The best confirmed ORR (≥PR) for all 149 patients was 53.7% (80/149), including 28.2% of patients with ≥VGPR and 7.4% with a CR, with a median time to response of 41.5 days. Surprisingly, ixa-based regimens demonstrated efficacy in pts with PI/len refractory diseases, with an ORR and ≥VGPR rate of 44.4% and 19.9% for PI-refractory pts, and an ORR and ≥VGPR rate of 30.6% and 12.2% for len-refractory pts. Pts eligible for MM1 study shown comparable ORR (76.7%) with that reported in MM1 (ORR 78%). No significant difference in response between different ixa-based regimens was observed. The median PFS of the whole cohort, pts with standard/high cytogenetic risks, pts refractory to bortezomib/len and pts eligible/ineligible for MM1 trial was 8.2, 8.2, 6.8, 6.7, 5.9months, not reached and 6.6months respectively. The median overall survival (OS) of the whole cohort and every subgroup was not reached. Adverse events (AEs) of grade 3/4, reported in 40 (27.2%) patients, included 10.1% thrombocytopenia, 5.4% anemia, 3.4% diarrhea and 6.0% pneumonia. Only 3 (2.01%) pts had a grade 3/4 peripheral neuropathy during follow-up. Discussion and conclusion: Our results show that ixa-based therapy demonstrated good efficacy with limited toxicity for pts with RRMM in real-life clinical practice. Moreover, in pts with PIs- or len- refractory diseases, ixa-based therapy still showed acceptable effectiveness (ORR: 44.4% and 30.6%; mPFS: 6.7 months and 5.9 months). Although 70.5% pts in our real-life cohort were ineligible for MM1 trial, the efficacy and safety profile is similar to that reported in MM1 China Continuation Study. Ixa-based therapy is a reasonable choice for Chinese RRMM pts. Disclosures No relevant conflicts of interest to declare.

scholarly journals Ixazomib-Based Frontline Therapy in Patients with Newly Diagnosed Multiple Myeloma in Real-Life Practice Showed Comparable Efficacy and Safety Profile with Those Reported in Randomized Clinical Trials: A Multi-Center Study in China

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3181-3181
Author(s):  
Jing Li ◽  
Li Bao ◽  
Zhong-jun Xia ◽  
Sili Wang ◽  
Xin Zhou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Safety Profile ◽  
Phase 1 ◽  
Real Life ◽  
Routine Practice ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Frontline Therapy ◽  
Grade 3

Jing Li, Li Bao and Zhong-jun Xia contributed equally to this study. Background: Ixazomib (ixa) is the first oral proteasome inhibitor that approved for the use in patients with relapsed/refractory multiple myeloma (RRMM) in > 60 countries. In a recently reported long-term result of a phase 1/2 study (NCT01217957), the all-oral triplet regimen of ixazomib plus Rd (IRd) demonstrated favorable efficacy with acceptable toxicity in patients with newly diagnosed MM (NDMM). Meanwhile, a large phase 3 trial (TOURMALINE-MM2, NCT01850524) evaluating IRd in stem-cell transplantation (SCT) ineligible NDMM patients is ongoing. However, outcomes and toxicity profiles of novel-agent-based MM therapies in real world practice often differ from data reported in clinical trials and data of the efficacy of ixa-based treatment in NDMM in routine practice is currently missing. Aims and Methods: To assess the efficacy and safety profile of ixa-based frontline therapy in NDMM patients in routine practice, we performed a large national, multi-center, observational study enrolling ixa-treated (at least one cycle completed) NDMM patients from 14 China centers. Clinical records on demographics, disease characteristics, treatment regimen and duration, response rate, adverse events (AEs), and treatment discontinuations and survival were collected and analyzed. Results: A total of 60 NDMM patients treated with ixa-based regimens were included. Ixa-based regimens included IRd in 23 (38.3%) patients, the ixa and dexamethaxone (Id) in 17 (28.3%) patients and Id plus chemotherapeutics/other agents (Adriamycin in 12 patients, cyclophosphamide in 5 patients, and thalidomide in 3 patients) in 20 (33.3%). None of the patients included received SCT during follow-up. Median age was 69 years (range 35 - 85) with 33 (55.0%) ≥65 years. At initial diagnosis, ISS stage I/II/III disease were presented in 21.7%/28.3%/50.0% patients at initial diagnosis; high-risk cytogenetic abnormalities (including del 17p, t(4;14), and/or t(14;16) detected by fluorescence in situ hybridization) were detected in 9 patients (19.6%, among 46 patients with FISH results). Twenty-six (43.4%) patients had a ECOG PS ≥2 and 5 patients (8.3%) had extramedullary disease. Eighteen patients were not eligible for ixa phase 1/2 study (NCT01217957) according to its inclusion and exclusion criteria, and even more patients (36, 60%) were not eligible for TOURMALINE-MM2 study. (Table1). The best confirmed ORR (partial response or better) for all 60 patients was 93.3% (56/60), including 63.3% of patients with ≥VGPR and 20.0% with a CR. The median time to response was 41 days. Similar response was observed among different subgroups: the ORR in Ixa phase1/2 study-eligible/ineligible group, MM2 trial- eligible/ineligible group and patients with standard/high-risk cytogenetics was 95.2%, 88.9%, 91.7%, 94.4%, 91.9% and 100.0%, respectively. And no significant difference in response between different ixa-based regimens was observed. After a median follow-up of 137.5 days after the first dose of ixazomib treatment (range, 28 - 372), median overall survival (mOS) and progression-free survival (mPFS) were not reached. (Table2) Adverse events (AEs) of grade 3 or higher were uncommon, reported in 14 (23.3%) patients, including thrombocytopenia (4 patients, 6.7%), diarrhea (5 patients, 8.3%), pneumonia (3 patients, 5.0%) and hypokalemia (1, 1.7%). No drug-related grade 3/4 peripheral neuropathy was recorded. Median cycles of ixa received were 4 cycles (range 1-11); 50 (83.3%) were still on treatment at data cut-off; 6 (10.0%) patients discontinued ixa due to intolerable AEs and 4 (6.7%) stop treatment for other reasons (mostly economic concerns). Discussion and conclusion: Here we reported the first real world, multi-center data on the efficacy and safety profile of ixa-based frontline therapy in patients with NDMM. Our results show that the ixa-based frontline therapy in real-life clinical practice is highly effective and fast in response, with an efficacy data (ORR 93.3%, ≥VGPR rate 63.3%) even better than that reported in NCT01217957 trial (ORR 88.0%, ≥VGPR rate 58.8%). Given the fact that no patients received SCT during follow-up in our cohort, our results maybe more comparable to the ongoing MM2 trial assessing SCT-ineligible NDMM. Ixa-based frontline therapy is well tolerated in NDMM patients treated in routine clinical practice. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Ixazomib is an oral proteasome inhibitor that approved for the use in patients with relapsed/refractory multiple myeloma (RRMM). Here in this abstract, I will present data on real-life practice of the use of ixazomib in newly diagnosed multiple myeloma.

LocoMMotion: A prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed/refractory multiple myeloma (RRMM) receiving ≥3 prior lines of therapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8041-8041
Author(s):  
Maria-Victoria Mateos ◽  
Katja Weisel ◽  
Valerio De Stefano ◽  
Aurore Perrot ◽  
Niels W.C.J. van de Donk ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real Life ◽  
Primary Objective ◽  
Standards Of Care ◽  
Efficacy And Safety ◽  
Standard Drug ◽  
The Us ◽  
Grade 3 ◽  
Line Of Therapy ◽  
Ecog Ps

8041 Background: Multiple myeloma (MM) remains incurable despite advances in medical treatment that have improved survival. Even with these improvements, most patients with MM eventually progress through standard drug classes of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), anti-CD38 monoclonal antibodies (mAbs), and others. There are currently no prospective data on real-world standard-of-care (SOC) in patients who progress after PIs, IMiDs, and anti-CD38 mAbs. Here, we present interim results from LocoMMotion (NCT04035226), the first prospective efficacy and safety study of real-life SOC in patients with RRMM. Methods: Eligible patients (aged ≥18 years [y]) with a diagnosis of MM were enrolled between August 2019 and October 2020 from 75 sites across 9 European countries and the US. Patients were included if they received ≥3 prior lines of therapy or were double-refractory to a PI and IMiD, had measurable disease at screening, received at least a PI, an IMiD, and anti-CD38 mAb with documented progressive disease since their last line of therapy, and had an ECOG PS score of 0 or 1. Responses were assessed per International Myeloma Working Group response criteria. A Response Review Committee assessed the overall response rate (ORR, primary objective) of real-life current SOC. Secondary objectives of the study included additional efficacy and safety evaluation of real-life SOC. Results: The data cut-off was November 4, 2020 for the first interim analysis of 225 patients with a median follow-up of 3.7 months (range: 0–12.7), 22 (9.8%) patients were from the US and 203 (90.2%) were from Europe. Median age was 68 y (range: 41–89), 124 (55.1%) were male, 162 (72.0%) had a baseline ECOG PS score of 1, and median time since initial MM diagnosis was 6.0 y (range: 0.3–22.8). Patients had received a median of 4.0 (range: 2–13) prior lines of therapy; all patients were triple-class exposed, 166 (73.8%) were triple-class refractory, and 208 (92.4%) were refractory to last line of therapy. The ORR with real-life SOC salvage therapy was 20.1% (95% CI: 15.0–26.0) in the response-evaluable population (n = 219). Treatment-emergent adverse events (TEAEs) were reported in 148 (65.8%) patients, 95 (42.2%) were grade ≥3. The most common grade ≥3 TEAEs were anemia, thrombocytopenia, and neutropenia. Fifteen deaths (6.7%) occurred due to TEAEs during the study. Treatment is ongoing in 121 (53.8%) patients. Conclusions: The interim results of this first, prospective study of real-life SOC treatment in heavily pretreated, triple-class exposed patients with RRMM demonstrate that patients continue to progress after multiple lines of therapy and have poor outcomes. Therefore, there is a need for new treatments with novel mechanisms of action for this patient population. Clinical trial information: NCT04035226.

scholarly journals OSSMAR: An Observational Study to Describe the Use of Sunitinib in Real-Life Practice for the Treatment of Metastatic Renal Cell Carcinoma

2019 ◽  
pp. 1-10 ◽  
Author(s):  
Marwan Ghosn ◽  
Roland Eid ◽  
Emad Hamada ◽  
Hamdy Abdel Azim ◽  
Jamal Zekri ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Clinical Practice ◽  
Middle East ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Real Life ◽  
Routine Clinical Practice ◽  
The Mean

PURPOSE Sunitinib offers improved efficacy for patients with metastatic renal cell carcinoma (mRCC). To provide better disease management in the Middle East, we studied its use in mRCC in real-life practice in this region. MATERIAL AND METHODS Patients diagnosed with mRCC and started on sunitinib between 2006 and 2016 from 10 centers in Africa and the Middle East region were studied in this regional, multicenter, observational, retrospective trial to obtain routine clinical practice data on the usage patterns and outcomes of sunitinib in mRCC in real-life practice. RESULTS A total of 289 patients were enrolled. Median age at diagnosis was 58.7 years. The patient characteristics were as follows: 73.6% of patients were males; 85.8% had clear-cell renal cell carcinoma (RCC); 97.5% had unilateral RCC; 66.3% had metastatic disease at initial diagnosis; 56.3% received previous treatment for RCC, among which 98.7% had undergone surgery; and 15.2% and 31.4% were classified in the favorable and poor-risk groups (expanded Memorial Sloan Kettering Cancer Center criteria), respectively. On treatment initiation, the mean total sunitinib dose was 48.1 mg, and 87.6% of patients were started on a sunitinib dose of 50 mg. The mean duration of sunitinib treatment was 9.6 months. Overall response rate was 20.8%, with a median duration of 8.2 months. Median time to progression was 5.7 months. Median follow-up time was 7.8 months. By months 12 and 24, 34.3% and 11.4% of patients, respectively, were still alive. Seventy-six patients (60.9%) experienced 314 adverse events. Twenty-three patients (8.0%) experienced 28 serious adverse events. Overall, 83 patients (28.7%) discontinued their sunitinib treatment. CONCLUSION The results are indicative of the general treatment outcomes of patients with mRCC in the Middle East using sunitinib in routine clinical practice. Reported adverse events are similar to those described in the literature but at lower frequencies.

scholarly journals Subcutaneous Administration of Bortezomib in Combination with Thalidomide and Dexamethasone for Treatment of Newly Diagnosed Multiple Myeloma Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Shenghao Wu ◽  
Cuiping Zheng ◽  
Songyan Chen ◽  
Xiaoping Cai ◽  
Yuejian Shi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Adverse Events ◽  
Subcutaneous Administration ◽  
Progression Free Survival ◽  
The Other ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Grade 3

Objective. To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma (MM) patients with the therapy of subcutaneous (subQ) administration of bortezomib and dexamethasone plus thalidomide (VTD) regimen.Methods. A total of 60 newly diagnosed MM patients were analyzed. 30 patients received improved VTD regimen (improved VTD group) with the subQ injection of bortezomib and the other 30 patients received conventional VTD regimen (VTD group).The efficacy and safety of two groups were analyzed retrospectively.Results. The overall remission (OR) after eight cycles of treatment was 73.3% in the VTD group and 76.7% in the improved VTD group (P>0.05). No significant differences in time to 1-year estimate of overall survival (72% versus 75%,P=0.848) and progression-free survival (median 22 months versus 25 months;P=0.725) between two groups. The main toxicities related to therapy were leukopenia, neutropenia, thrombocytopenia, asthenia, fatigue, and renal and urinary disorders. Grade 3 and higher adverse events were significantly less common in the improved VTD group (50%) than VTD group (80%,P=0.015).Conclusions. The improved VTD regimen by changing bortezomib from intravenous administration to subcutaneous injection has noninferior efficacy to standard VTD regimen, with an improved safety profile and reduced adverse events.

Response to Bortezomib in Combination after Relapse o Non-Response to First Treatment with Bortezomib Alone in Myeloma Multiple Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5094-5094
Author(s):  
Araceli Rubio-Martinez ◽  
Valle Recasens ◽  
Pilar Delgado ◽  
Juan Carlos Garcia-Zueco ◽  
Daniel Rubio-Felix ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Effects ◽  
Adverse Events ◽  
Second Line ◽  
Dexamethasone Group ◽  
Limited Experience ◽  
Grade 3 ◽  
Multiple Patients ◽  
Grade Iii

Abstract Background: Bortezomib has been shown to be effective in multiple myeloma (MM), but there is a limited experience in response to re-treatment. Aims: To evaluate the efficacy of Bortezomib in refractory/relapsed MM. Patients and methods: 41 patients treated with Bortezomib (1,3 mg/m2 on days 1,4,8,11 in a 21-day cycle) in second or more line as clinical practice protocol were included. The response was evaluated according EGBMT criteria (Bladé J, Samson D, Reece E et al). Patients that no have reached response after 4 courses or relapsed after CR or PR received a combination of: bortezomib+dexamethasone (group BD) or bortezomib+melphalan+prednisone (group BMP). Adverse effects were registered. Results: 39 valuable patients (males 43.0%). Mean age 59.9 years (34–82), over 65 years (66.6%). Bortezomib was administered in second line: 10 (25.6%), in third or more: 29 (74.3%). Overall Response: 76.4%: (CR+PR 70.5%, MR 5.9%), (CR 41.1%/CR-IFE negative 14.7%), Mean courses to reached response: 4.7. No relation to response and presence or not chromosomal aberrations. At 32 months on follow-up 9 patients had dead (26.4%) and 15 (44.1%) maintained response without therapy. In 17 patients (43.5%), a combination of BD (10 patients) or BMP (7 patients) were administrated by relapse or progression. Responses: group BD 6 PR, 3 NR; 1NV group BM P 3 PR, 3 NR, 1NV. Adverse events: thrombocytopenia 38.4 (grade III: 17.9), fatigue 38.5%, peripheral neuropathy 33.3, constipation 35.8%, diarrhea 20.5%, ZHV 12.8%, infection 33.3, pyrexia 10.2%, hypotension 5.1%, grade 3 leucopenia 12.8%. In 3 patients (7.6%) the therapy was disrupted by toxicity. We haven’t found any differences in adverse events in patients treated with bortezomib in combination. Conclusions: Related to the synergism of Bortezomib in combination, the re-treatment induces response (60%) in refractory MM without severe adverse effects. In spite of the scarce follow-up some patients could be benefit in re-treatment with Bortezomib. It is necessary to explore more combinations and to know the results of clinical trials. When there is not response after the 4th course of Bortezomib it is recommendable to use in combination

Bortezomib (Velcade ™) Observational Study in China: Efficacy and Safety of Bortezomib-Based Regimen in 395 Relapsed or Refractory Multiple Myeloma Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5179-5179
Author(s):  
Zhi-Xiang Shen ◽  
Hua Yan ◽  
Linna Wang
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Observational Study ◽  
Response Rate ◽  
Complete Response ◽  
Chinese Patients ◽  
Efficacy And Safety ◽  
Female Ratio ◽  
Bortezomib Treatment ◽  
Grade 3

Abstract Introduction: Multiple myeloma (MM) is a plasma-cell malignancy and overall survival for patients who have relapsed after initial therapy is approximately 2 years. Bortezomib (VELCADE TM) is a first-in-class proteasome inhibitor that has demonstrated significant anti-tumor activity in MM patients. Here we report the results of an observational study of the efficacy and safety of bortezomib-based regimens in Chinese relapsed/refractory MM patients. Methods: This was a multi-center, open-label, phase IV observational study designed to enroll 550 patients with relapsed or refractory MM. From Mar 2006 to May 2008, 500 patients with relapsed or refractory MM were enrolled from 43 medical centers in China and 395 of them were evaluated. Bortezomib (0.7 to 1.6 mg/m2 i.v.) was given on days 1, 4, 8, and 11 in in a 21-day cycle, up to a maximum of 8 cycles, combined with other agents, mainly with the addition of dexamethasone (60.1%). Major endpoint included response rate, safety and time to response. Responses of 62% patients were determined by European Group for Blood and Marrow Transplantation criteria (EBMT). Bortezomib withheld if patients developed neutropenia fever, grade 4 haematologic adverse events (AEs), or grade 3 non-haematologic AEs, and re-administered at 75% of the initial dosage after recovery. Results: In 395 evaluable cases, the median age was 59 years (range 35–82) and the male/female ratio was 1.5:1. 90% of patients were in late stage(stage II/III) and 50% of them were IgG subtype. Patients had received various prior therapies before bortezomib treatment, including VAD (31.3%), VBMCP (M2, 15.1%) and thalidomide-based regimens(14.9%), with best response rate of 10.4% complete response (CR) and 42.3% partial response (PR) from prior therapies. 311 (82%) cases of patients received 1.0–1.4mg/m2 bortezomib-based regimens treatment and 38.5% of them received at least 4 cycles of treatment. 364 patients were evaluable for response, the overall response rate was 287/364 (78.8%), 89 patients (24.5%) achieved a CR, 30(8.24%) had a nearly complete response (nCR), 168 (46.2%) had a PR, 39 (10.7%) had minimal response (MR), 24 (6.6%) had stable disease (SD), and the other 14 (3.9%) had progressive disease (PD). Median time to response was 1 cycle of treatment (range 1–6). Patients who received 4 or more cycles of bortezomib treatment achieved a higher response rate (CR+PR: 81.5%) compared to those who received fewer cycles (partly due to adverse events). And prognosis-related analysis showed that the dosage of bortezomib at 1.0 mg/m2 or more had a significant influence on the time to response and response rate, but no obvious effect on response duration, time to progress or the survival time. Drug related adverse events (AEs) were reported in 50.4% of patients during treatment, including hematologic AEs (mainly thrombocytopenia, 22.5%), gastrointestinal AEs (24.8%), and peripheral neuropathy (22.5%). The rates of grade 3–4 AEs of them were 46.1%, 11.2% and 15.7%, respectively. Serious AEs occurred in 33 (8.4%) cases and 23 (70%) patients recovered finally. Most AEs were predictable and manageable. Conclusion: Bortezomib-based regimen is effective treatment with higher response rate and is well tolerated in most Chinese patients with relapsed and refractory MM patients. Long-term follow-up is continuing.

Phase 1/2 Trial Of Lenalidomide In Combination With Cyclophosphamide and Prednisone (REP) In Patients With Lenalidomide-Refractory Multiple Myeloma (REPEAT-study)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 287-287 ◽  
Author(s):  
Inger S. Nijhof ◽  
Sonja Zweegman ◽  
Mark-David Levin ◽  
Harry R. Koene ◽  
Aart Beeker ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Dose Level ◽  
Research Funding ◽  
Phase 1 ◽  
Oral Cyclophosphamide ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Grade 3 ◽  
Dose Levels

Abstract Background The outcome of multiple myeloma (MM) patients who are no longer responding to thalidomide, lenalidomide (LEN) and bortezomib (BORT) is very poor, with a median event-free survival of 5 months and median overall survival (OS) of 9 months (Kumar SK et al, Leukemia 2012; 26;149-157). We have previously shown in a small retrospective study that the combination of continuous low dose oral cyclophosphamide (endoxan) and prednisone combined with lenalidomide (REP) had remarkable activity in heavily pretreated LEN-refractory multiple myeloma patients (median 6 lines of previous chemotherapy) (vd Donk et al; Br J Haematol 2010;148(2):335-7). To determine the optimal dose of lenalidomide with continuous cyclophosphamide and prednisone, we initiated a prospective study to evaluate the maximum tolerated dose (MTD) of the REP regimen and to assess its efficacy and safety in LEN-refractory MM patients. Here we report safety and efficacy data from the phase 1 dose-escalation part of the REPEAT-study (NCT01352338). Patients and Methods Patients aged ≥ 18 years with LEN-refractory MM, ECOG-performance status 0-3 and adequate kidney, liver and hematologic function were included. Five dose levels were evaluated using a standard 3+3 design, based on dose-limiting toxicities (DLTs) occurring in cycle 1. Patients received LEN in doses ranging from 10-25 mg/day on days 1-21 of 28-day cycle, while oral cyclophosphamide (50 or 100 mg) and prednisone (20 mg) were given continuously. Therapy was continued until progression. The MTD for the phase 2 part is defined as the highest dose level with 0 or 1 DLT's observed in 6 patients. Results Up till now, 35 patients were enrolled (22 in phase 1 and 13 in phase 2) from August 2011 to June 2013. The phase 2 part is still recruiting and data are not evaluable yet. One patient in phase 1 was excluded because of study violation and is not included in the analysis. The median age of the 21 evaluable patients in phase 1 was 69 years (range 41-73); 76% were male. The median duration of the disease from diagnosis was 41 months (range 18-96), median number of prior therapies was 3 (range 2-6), and 12 patients (57%) had previously received autologous SCT. All patients were LEN-refractory, 19 (90%) had prior BORT treatment, and 16 (76%) had BORT-refractory MM. Fifty-five % of the patients were considered high risk by FISH. At the time of analysis, 16 of 21 patients in phase 1 have discontinued treatment because of disease progression (13), alternative treatment (allo-SCT) (1), or adverse events (2). The MTD was defined as LEN 25 mg days 1-21 of a 28-day cycle, combined with oral cyclophosphamide 50 mg and prednisone 20 mg continuously (dose level 4), based on three patients experiencing a DLT: two developed pneumonia (in dose levels 4 and 5; CTC grade 3), and one patient at dose level 5 experienced CTC grade 3 dyspnea. Neutropenia (18%) and thrombocytopenia (18%) were the most common grade 3 hematological adverse events (AEs), which were managed with growth factor support and/or dose modification. There were no grade 4 hematologic AEs. Grade 3 respiratory tract infections (29%) and grade 2 fatigue (19%) were the most common non-hematological AEs. Venous thromboembolism occurred in 1 patient. Figure 1 shows a waterfall plot of the responses of the patients that participated in the phase 1 part of the study. Overall response rate (≥ PR) was 67% with 6 out of 21 (29%) patients achieving at least VGPR. In addition 2 patients achieved MR (≥ MR: 76%). Median PFS and OS were 6.3 and 15.5 months respectively. Similar results were achieved in the subset of patients with LEN- and BORT-refractory disease. Interestingly, laboratory experiments with purified myeloma cells from these patients suggest synergism between LEN and cyclophosphamide. Conclusions The REP regimen induces high response rates and prolonged PFS and OS in LEN-refractory patients with acceptable toxicity. The MTD is defined as LEN 25 mg days 1-21 of a 28-day cycle, combined with oral cyclophosphamide 50 mg and prednisone 20 mg continuously. Phase 2 is enrolling patients and evaluates efficacy and safety of the REP regimen at the MTD. REP should be considered a valuable salvage option for LEN-refractory MM patients. We will present an updated follow-up at ASH. Disclosures: Sonneveld: Onyx: Research Funding; Millenium: Research Funding; Janssen-Cilag: Research Funding; Onyx: Honoraria; Celgene: Honoraria; Janssen-Cilag: Honoraria; Celgene: Research Funding. Lokhorst:Genmab A/S: Consultancy, Research Funding; Celgene: Honoraria; Johnson-Cilag: Honoraria; Mudipharma: Honoraria. van de Donk:Celgene: Research Funding.

The Efficacy and Safety of Immunomodulatory Drugs in Multiple Myeloma Maintenance Therapy: Results of a Meta-Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3477-3477
Author(s):  
Yucai Wang ◽  
Fang Yang ◽  
Wenwen Zhang ◽  
Xiaoxiang Guan ◽  
Neil Kothari ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
Random Effect Model ◽  
Immunomodulatory Drugs ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Grade 3

Abstract Objective: To evaluate the efficacy and safety of immunomodulatory drugs (IMiDs) in maintenance therapy of multiple myeloma through meta-analysis of randomized controlled trials (RCTs). Patients and methods: PubMed, Web of Science, ASCO, ESMO and ASH databases were searched for RCTs that investigated the treatment outcomes (overall survival [OS], progression-free survival [PFS] and/or event-free survival [EFS] and/or time to progression [TTP]) of maintenance therapy with IMiDs in patients with multiple myeloma. Study endpoints included OS, PFS/EFS/TTP, and grade 3 or 4 adverse events. Pooled hazard ratios (HRs) for survival outcomes and risk ratios (RRs) for dichotomous data with 95% confidence interval (CI) were calculated using Comprehensive MetaAnalysis (v2). The random-effect model was utilized in view of clinical heterogeneity in the study population. Results: Eighteen RCTs comprising a total of 6562 patients were included in this meta-analysis. IMiDs used in the RCTs included thalidomide (14 trials) and lenalidomide (4 trials). Overall, IMiD-based maintenance therapy significantly improved OS (HR = 0.91, 95% CI = 0.84 - 0.99, P = 0.027) and PFS (HR = 0.63, 95% CI = 0.60 - 0.68, P < 0.001). Notably, IMiDs maintenance therapy increased OS in the setting of ASCT but showed no OS prolongation without ASCT. On further stratification, thalidomide-based maintenance therapy demonstrated OS benefit only in the setting of ASCT, while lenalidomide-based maintenance therapy did not show OS benefit regardless of transplantation status. For PFS however, both thalidomide- and lenalidomide-based maintenance therapies demonstrated significant survival benefits, regardless of transplantation status (Table 1). IMiD-based maintenance therapy increased the risk of developing grade 3 or 4 neutropenia (RR = 3.04, 95% CI = 2.49 - 3.70, P < 0.001), thrombocytopenia (RR = 2.68, 95% CI = 1.90 - 3.79, P < 0.001), anemia (RR = 1.97, 95% CI = 1.23 - 3.15, P = 0.005), infection (RR = 1.53, 95% CI = 1.22 - 1.92, P < 0.001), fatigue (HR = 1.71, 95% CI = 1.24 - 2.36, P = 0.001), constipation (RR = 2.04, 95% CI = 1.15 - 3.62, P = 0.015), and peripheral neuropathy (RR = 2.02, 95% CI = 1.20 - 3.39, P = 0.008). Conclusions: IMiD-based maintenance therapy results in significant improvement in OS and PFS in multiple myeloma patients but increased the risk of developing some grade 3 or 4 adverse events. While thalidomide-containing maintenance therapy regimens showed OS benefits in the setting of ASCT, lenalidomide-containing maintenance therapy did not prolong OS regardless of transplantation status. Both thalidomide- and lenalidomide-based maintenance therapies increased PFS in multiple myeloma patients independent of transplantation status. When more data on lenalidomide and the newer agent pomalidomide become available, further analysis will be warranted to analyze the efficacy and safety of IMiDs in multiple myeloma maintenance therapy. Table 1. Effects of IMiD-based maintenance therapy on OS and PFS in multiple myeloma patients IMiD ASCT status Survival Number of trials HR 95% CI P value Thalidomide/Lenalidomide combined OS 18 0.91 0.84 - 0.99 0.027 with ASCT OS 10 0.88 0.78 - 0.99 0.036 without ASCT OS 9 0.94 0.83 - 1.06 0.299 Thalidomide combined OS 14 0.92 0.84 - 1.01 0.090 with ASCT OS 8 0.87 0.77 - 1.00 0.049 without ASCT OS 7 0.97 0.85 - 1.10 0.640 Lenalidomide combined OS 4 0.84 0.67 - 1.04 0.102 with ASCT OS 2 0.89 0.66 - 1.20 0.457 without ASCT OS 2 0.78 0.57 - 1.06 0.114 Thalidomide/Lenalidomide combined PFS 17 0.63 0.60 -0.68 < 0.001 with ASCT PFS 9 0.62 0.57 - 0.67 < 0.001 without ASCT PFS 9 0.66 0.60 - 0.73 < 0.001 Thalidomide combined PFS 13 0.67 0.63 - 0.72 < 0.001 with ASCT PFS 7 0.66 0.60 - 0.72 < 0.001 without ASCT PFS 7 0.69 0.62 -0.77 < 0.001 Lenalidomide combined PFS 4 0.50 0.43 - 0.58 < 0.001 with ASCT PFS 2 0.49 0.41 - 0.58 < 0.001 without ASCT PFS 2 0.52 0.40 - 0.67 < 0.001 Disclosures No relevant conflicts of interest to declare.

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]

Safety of a trastuzumab biosimilar, used under routine clinical practice conditions in adult HER2+ breast cancer patients in Morocco.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13024-e13024
Author(s):  
Hassan Errihani ◽  
Narjiss Berrada ◽  
Mouna Khouchani ◽  
Abdelkader Acharki ◽  
Kamal Lahbabi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Practice ◽  
Adverse Events ◽  
Early Breast Cancer ◽  
Real World ◽  
Safety Profile ◽  
Safety Data ◽  
Routine Clinical Practice ◽  
Her2 Breast Cancer

e13024 Background: Hertraz, the first trastuzumab biosimilar was approved in Morocco in 2017. Real world data on trastuzumab biosimilars are very limited or not available. HERLife is a prospective, non-interventional phase IV study program that investigated the experience of using Hertraz, a biosimilar for trastuzumab (Herceptin), under routine clinical practice conditions in Morocco. The primary aim of this study was to confirm the acceptable safety and tolerability of Hertraz. Methods: Ninety-nine patients with HER2-positive breast cancer treated with Hertraz were enrolled from 8 public and private sector hospitals and followed up for 12 months as part of this non-interventional study. Cardiac events (LVEF) and other unexpected or serious adverse events were monitored. The study arms consisted of patients with early breast cancer (Arm 1, n=70) and metastatic breast cancer (Arm 2, n=29) whose median age was 53 years in both groups. Results: Switching from Herceptin to Hertraz was observed in 45% of 29 MBC patients and 27% of 70 EBC patients. Switching was done at a median of 4th cycle. Pertuzumab was used in combination with Hertraz in 69% and 19% of patients in the metastatic and neoadjuvant settings, respectively. Two patients had a decline in LVEF. One patient treated with Hertraz alone and one patient treated with Hertraz and pertuzumab developed a decrease in LVEF requiring a three-week treatment discontinuation of Hertraz. Treatment of Hertraz was continued after 1 skipped cycle without occurrence of new side effects. No other trastuzumab related adverse events was observed. Four patients in the metastatic group and 2 patients in the early breast cancer arm had a relapse in the 12 months of clinical follow-up. Conclusions: The management of HER2+ breast cancer in Morocco follows the international recommendations. This is the first real world safety data of Hertraz from Morocco. The 12-month follow-up treatment with Hertraz showed an acceptable cardiac safety profile. In cases where there was a switch from Herceptin to Hertraz or Hertraz combined with pertuzumab, the safety profile was similar to that previously reported in other studies.

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