scholarly journals Salvage therapy with “Dara‐KDT‐P(A)CE” in heavily pretreated, high‐risk, proliferative, relapsed/refractory Multiple Myeloma

2021 ◽  
Author(s):  
Xiang Zhou ◽  
Anna Ruckdeschel ◽  
Jessica Peter ◽  
David Böckle ◽  
Hannah Hornburger ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Salvage Therapy ◽  
Refractory Multiple Myeloma ◽  
Heavily Pretreated

scholarly journals Pmd-107: Marizomib, Pomalidomide and Low Dose-Dexamethasone Combination Study in Relapsed/Refractory Multiple Myeloma (NCT02103335): Full Enrollment Results from a Phase-1 Multicenter, Open Label Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3326-3326 ◽  
Author(s):  
Andrew Spencer ◽  
Simon Harrison ◽  
Jacob P. Laubach ◽  
Jeffrey Zonder ◽  
Ashraf Z Badros ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Low Dose ◽  
Employment Equity ◽  
Advisory Committees ◽  
Refractory Multiple Myeloma ◽  
Heavily Pretreated ◽  
Equity Ownership

Abstract Marizomib (MRZ) is a novel, irreversible, pan subunit proteasome inhibitor (PI) with preclinical evidence demonstrating in vitro and in vivo activity in multiple myeloma (MM). This study was designed to evaluate the safety and antimyeloma activity of pomalidomide (POM), MRZ and low dose dexamethasone (Lo-DEX) (PMD) in patients with relapsed and refractory multiple myeloma (RRMM). Thirty-eight heavily pretreated patients with RRMM were enrolled [dose-escalation cohort (n=14); recommended Phase 2 dose (RP2D) cohort (n=24)]. IV MRZ (0.3 to 0.5 mg/m2) was administered on Days (D) 1, 4, 8, 11; POM (3 or 4 mg) on D1 through 21; and Lo-DEX (5 or 10 mg) on D1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22, 23 of every 28-D cycle. Patients received a median of 4 (range 1-9) prior lines of therapy; 100% received prior lenalidomide (LEN) and bortezomib (BTZ), 34% carfilzomib (CFZ), and 50% thalidomide. 53% of patients were refractory to both LEN and BTZ and 21% were refractory to LEN, BTZ, and CFZ. There were no dose limiting toxicities during the study. The most common study treatment related ≥Grade 3 adverse events (AEs) were neutropenia (11/38 pts: 29%), pneumonia (4/38 pts 11%), anemia (4/38 pts; 11%), thrombocytopenia (4/38 pts; 11%), and febrile neutropenia (2/38 pts; 5%), with two grade 4 AEs (neutropenia related to POM and viral infection related to DEX), and one grade 5 AE (cardio-respiratory arrest from a suspected PE related to POM). Overall, MRZ was well tolerated, did not add to the incidence or severity of POM/Lo-DEX AEs and the regimen may have fewer hematological and infectious AEs compared to that observed with POM/Lo-DEX. MRZ pharmacokinetic analysis revealed that it was rapidly cleared with a short T1/2 (6.2-11mins) and a large volume of distribution (41-86L) suggesting extensive tissue distribution. Pharmacodynamic analysis demonstrated rapid and robust inhibition of chymotrypsin-like activity in both packed whole blood (PWB) and peripheral blood mononuclear cells (PMBCs), reflecting the irreversible binding nature of MRZ. Evolving inhibition of trypsin-like and caspase-like proteasome activity was also observed in PWB and PBMC with continued dosing. The overall response rate (ORR) and clinical benefit rate (CBR) for the 36 response evaluable patients was 53% (19/36) and 64% (23/36), respectively (Table 1). Subpopulation analysis demonstrated an ORR of 50% (5/10) in high risk cytogenetic patients, 56% (10/18) in LEN/BTZ refractory patients, 71% (5/7) in LEN/BTZ/CFZ refractory patients and 80% (8/10) in CFZ refractory patients. These data compare favorably against POM/Lo-Dex with a near doubling of ORR in both the total patient population and the double refractory patients. Substantial activity in high-risk patients that are triple refractory and in patients that are refractory to CFZ in prior last regimen was observed. MRZ activity in RRMM patients exposed and/or refractory to multiple PIs is likely a consequence of its unique pan proteasome subunit inhibitory actions. In conclusion, MRZ in combination with POM and Lo-DEX was well tolerated and demonstrated promising activity in heavily pretreated, high-risk RRMM patients. Table 1 Table 1. Disclosures Harrison: Janssen-Cilag: Research Funding, Speakers Bureau; Celgene: Honoraria. Zonder:Prothena: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Pharmacyclics: Other: DSMC membership. Khot:Amgen: Honoraria; Janssen: Consultancy; Pfizer: Speakers Bureau. Anderson:C4 Therapeutics: Equity Ownership; Millennuim: Membership on an entity's Board of Directors or advisory committees; Oncoprep: Equity Ownership; C4 Therapeutics: Equity Ownership; Gilead: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Acetylon: Equity Ownership; Acetylon: Equity Ownership; Oncoprep: Equity Ownership; Millennuim: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees. MacLaren:Triphase Accelerator: Employment, Equity Ownership. Reich:Triphase Accelerator: Consultancy. Trikha:Encycle Therapeutics: Consultancy, Equity Ownership; Triphase Accelerator: Employment, Equity Ownership. Richardson:Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals The role of idecabtagene vicleucel in patients with heavily pretreated refractory multiple myeloma

2021 ◽  
Vol 12 ◽  
pp. 204062072110196
Author(s):  
Albert Oriol ◽  
Laura Abril ◽  
Anna Torrent ◽  
Gladys Ibarra ◽  
Josep-Maria Ribera
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Safety Profile ◽  
Proteasome Inhibitors ◽  
Clinical Development ◽  
Phase Iii ◽  
Acceptable Safety Profile ◽  
Refractory Multiple Myeloma ◽  
High Risk Patients ◽  
Risk Patients

The development of several treatment options over the last 2 decades has led to a notable improvement in the survival of patients with multiple myeloma. Despite these advances, the disease remains incurable for most patients. Moreover, standard combinations of alkylating agents, immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies targeting CD38 and corticoids are exhausted relatively fast in a proportion of high-risk patients. Such high-risk patients account for over 20% of cases and currently represent a major unmet medical need. The challenge of drug resistance requires the development of highly active new agents with a radically different mechanism of action. Several immunotherapeutic modalities, including antibody–drug conjugates and T-cell engagers, appear to be promising choices for patients who develop resistance to standard combinations. Chimeric antigen-receptor-modified T cells (CAR-Ts) targeting B-cell maturation antigen have demonstrated encouraging efficacy and an acceptable safety profile compared with alternative options. Multiple CAR-Ts are in early stages of clinical development, but the first phase III trials with CAR-Ts are ongoing for two of them. After the recent publication of the results of a phase II trial confirming a notable efficacy and acceptable safety profile, idecabtagene vicleucel is the first CAR-T to gain regulatory US Food and Drug Administration approval to treat refractory multiple myeloma patients who have already been exposed to antibodies against CD38, proteasome inhibitors, and immunomodulatory agents and who are refractory to the last therapy. Here, we will discuss the preclinical and clinical development of idecabtagene vicleucel and its future role in the changing treatment landscape of relapsed and refractory multiple myeloma.

P-084: Venetoclax monotherapy is feasible and efficient in patients with bcl-2 overexpressing relapsed/refractory multiple myeloma at high-risk sites: a case series

2021 ◽  
Vol 21 ◽  
pp. S85
Author(s):  
David Cordas dos Santos ◽  
Elena Stauffer ◽  
Tanja Paul ◽  
Martina Rudelius ◽  
Sebastian Theurich
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Case Series ◽  
Refractory Multiple Myeloma

Efficacy of daratumumab monotherapy in real-world heavily pretreated patients with relapsed or refractory multiple myeloma

2019 ◽  
Vol 64 (2) ◽  
pp. 349-355 ◽  
Author(s):  
Aleksander Salomon-Perzyński ◽  
Adam Walter-Croneck ◽  
Lidia Usnarska-Zubkiewicz ◽  
Dominik Dytfeld ◽  
Patrycja Zielińska ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Refractory Multiple Myeloma ◽  
Heavily Pretreated ◽  
Pretreated Patients

Outcomes of VD-PACE With Immunomodulatory Agent as a Salvage Therapy for Relapsed/Refractory Multiple Myeloma

2020 ◽  
Author(s):  
Al-Ola Abdallah ◽  
Monia Sigle ◽  
Ghulam Rehman Mohyuddin ◽  
Emily Coggins ◽  
Cassie Remker ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Salvage Therapy ◽  
Refractory Multiple Myeloma ◽  
Immunomodulatory Agent

scholarly journals D(T)PACE as salvage therapy for aggressive or refractory multiple myeloma

2013 ◽  
Vol 161 (6) ◽  
pp. 802-810 ◽  
Author(s):  
Alina S. Gerrie ◽  
Joseph R. Mikhael ◽  
Lu Cheng ◽  
Haiyan Jiang ◽  
Vishal Kukreti ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Salvage Therapy ◽  
Refractory Multiple Myeloma

Phase II study of the combination of daratumumab, ixazomib, pomalidomide, and dexamethasone as salvage therapy in relapsed/refractory multiple myeloma

2019 ◽  
Vol 19 (10) ◽  
pp. e360
Author(s):  
Caitlin Costello ◽  
Edward Ball ◽  
Carolyn Mulroney ◽  
Michelle Padilla
Keyword(s):  
Multiple Myeloma ◽  
Phase Ii ◽  
Salvage Therapy ◽  
Phase Ii Study ◽  
Refractory Multiple Myeloma

scholarly journals Carfilzomib Based Treatment Strategies in the Management of Relapsed/Refractory Multiple Myeloma with Extramedullary Disease

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1035 ◽  
Author(s):  
Xiang Zhou ◽  
Patricia Flüchter ◽  
Katharina Nickel ◽  
Katharina Meckel ◽  
Janin Messerschmidt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Response Rate ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Serological Response ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Extramedullary Disease ◽  
Heavily Pretreated ◽  
Pretreated Patients

Published experience with carfilzomib in patients with relapsed/refractory multiple myeloma (RRMM) and extramedullary disease (EMD) is still limited. The current study aimed to assess the efficacy and safety of carfilzomib containing therapy regimens in EMD. We retrospectively analyzed 45 patients with extramedullary RRMM treated with carfilzomib from June 2013 to September 2019. The median age at the start of carfilzomib was 64 (range 40–80) years. Twenty (44%) and 25 (56%) patients had paraosseous manifestation and EMD without adjacency to bone, respectively. The serological overall response rate (ORR) was 59%. Extramedullary response was evaluable in 33 patients, nine (27%) of them achieved partial remission (PR) (ORR = 27%). In 15 (33%) patients, we observed no extramedullary response despite serological response. The median progression-free survival (PFS) and overall survival (OS) were five (95% CI, 3.5–6.5) and ten (95% CI, 7.5–12.5) months, respectively. EMD without adjacency to bone was associated with a significantly inferior PFS (p = 0.004) and OS (p = 0.04) compared to paraosseous lesions. Carfilzomib based treatment strategies showed some efficacy in heavily pretreated patients with extramedullary RRMM but could not overcome the negative prognostic value of EMD. Due to the discrepancy between serological and extramedullary response, evaluation of extramedullary response using imaging is mandatory in these patients.

MM-234: Outcomes of VDPACE with an Immunomodulatory Agent (IMiD) as a Salvage Therapy in Relapsed/Refractory Multiple Myeloma (RRMM) with Extramedullary Disease (EMD)

2020 ◽  
Vol 20 ◽  
pp. S302-S303
Author(s):  
Al-Ola Abdallah ◽  
Shebli Atrash ◽  
Zahra Mahmoudjafari ◽  
Joseph McGuirk ◽  
Siddhartha Ganguly
Keyword(s):  
Multiple Myeloma ◽  
Salvage Therapy ◽  
Refractory Multiple Myeloma ◽  
Immunomodulatory Agent ◽  
Extramedullary Disease

Salvage Therapy With Thalidomide In Patients With Advanced Relapsed/Refractory Multiple Myeloma

2002 ◽  
Vol 7 (3) ◽  
pp. 209-209 ◽  
Author(s):  
P Tosi ◽  
E Zamagni ◽  
C Cellini ◽  
S Ronconi ◽  
F Patriarca ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Salvage Therapy ◽  
Refractory Multiple Myeloma
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