Impact of prior treatment on patients with relapsed multiple myeloma treated with carfilzomib and dexamethasone vs bortezomib and dexamethasone in the phase 3 ENDEAVOR study

Moreau, Philippe; Joshua, Douglas; Wj, Chng; Palumbo, Antônio; Goldschmidt, Hartmut; Hájek, Roman; Façon, Thierry; Ludwig, Heinz; Pour, Luděk; Niesvizky, Rubén; Oriol, Albert; Rosiñol, Laura; Suvorov, Aleksandr; Gaïdano, Gianluca; Pika, Tomáš; Weisel, Katja; Goranova-Marinova, Vesselina; Gillenwater, HH; Mohamed, Nehal; Aggarwal, Sanjay; Feng, Shibao; Dimopoulos, Meletios Α.

doi:10.1038/leu.2016.186

Cited by 68 publications

(77 citation statements)

References 19 publications

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“…Previous studies have investigated the efficacy of carfilzomib in subgroups of patients categorized by line of therapy and have demonstrated that patients benefit from receiving carfilzomib at first relapse (and this benefit may be greater than that obtained from use of carfilzomib at second or third relapse). In the ENDEAVOR trial, patients who received Kd at first relapse had a median PFS of 22.2 months, while patients who received Kd at second or third relapse had a median PFS of 14.9 months . In comparison with the control arm (Rd), risk of progression or death was reduced by approximately 55% among patients who received carfilzomib at first relapse and by approximately 40% among patients who received carfilzomib at second or third relapse .…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have investigated the efficacy of carfilzomib in subgroups of patients categorized by number of previous lines of therapy, and among subgroups of patients with or without prior exposure to a proteasome inhibitor. In both ASPIRE and ENDEAVOR, patients who received carfilzomib‐containing regimens had improved median PFS compared with control groups regardless of whether patients were previously exposed to proteasome inhibitors . Additionally, patients who received carfilzomib at first relapse had a significant and clinically relevant improvement in PFS compared with patients who received standard of care at first relapse in both ASPIRE and ENDEAVOR .…”

Section: Introductionmentioning

confidence: 98%

“…In both ASPIRE and ENDEAVOR, patients who received carfilzomib‐containing regimens had improved median PFS compared with control groups regardless of whether patients were previously exposed to proteasome inhibitors . Additionally, patients who received carfilzomib at first relapse had a significant and clinically relevant improvement in PFS compared with patients who received standard of care at first relapse in both ASPIRE and ENDEAVOR . In this study, we performed post hoc analyses of ENDEAVOR and ASPIRE to investigate the efficacy of carfilzomib among patients who had early or late relapse following the most recent therapy.…”

Section: Introductionmentioning

confidence: 99%

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Carfilzomib in relapsed or refractory multiple myeloma patients with early or late relapse following prior therapy: A subgroup analysis of the randomized phase 3 ASPIRE and ENDEAVOR trials

Mateos

Goldschmidt

Miguel

et al. 2018

Hematological Oncology

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We performed analyses of the randomized phase 3 ASPIRE and ENDEAVOR trials to investigate the efficacy of carfilzomib among subgroups of relapsed or refractory multiple myeloma patients who had early or late disease relapse following initiation of the immediately prior therapy. In ASPIRE and ENDEAVOR, patients had received 1 to 3 prior lines of therapy. Patients in ASPIRE received carfilzomib, lenalidomide, and dexamethasone (KRd) or lenalidomide and dexamethasone (Rd), and patients in ENDEAVOR received carfilzomib and dexamethasone (Kd) or bortezomib and dexamethasone (Vd). Patients with relapse ≤1 year after initiating the most recent prior line of therapy were categorized as early relapsers, and patients with relapse after >1 year were categorized as late relapsers. The median progression-free survival (PFS) in ASPIRE for early relapsers was 21.4 months for KRd vs 10.7 months for Rd (hazard ratio [HR]: 0.714; 95% confidence interval [CI]: 0.508-1.004; P = 0.0257), and for late relapsers was 29.7 months for KRd vs 18.2 months for Rd (HR: 0.675; 95% CI: 0.533-0.854; P = 0.0005). The overall response rate (ORR) for early relapsers was 83.2% for KRd vs 54.8% for Rd, and for late relapsers was 89.0% for KRd vs 69.7% for Rd. The median PFS in ENDEAVOR (Kd vs Vd) for early relapsers was 13.9 months vs 5.7 months (HR: 0.598; 95% CI: 0.423-0.846; P = 0.0017), and for late relapsers was 22.2 months vs 10.2 months (HR: 0.486; 95% CI: 0.382-0.620; P < 0.0001). The ORR (Kd vs Vd) for early relapsers was 63.4% vs 49.1% and for late relapsers was 81.8% vs 66.8%. In conclusion, patients with relapsed or refractory multiple myeloma who received carfilzomib-containing regimens had improved PFS and ORR compared with control groups, regardless of whether they had an early or late relapse following the most recent prior therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Carfilzomib in relapsed or refractory multiple myeloma patients with early or late relapse following prior therapy: A subgroup analysis of the randomized phase 3 ASPIRE and ENDEAVOR trials

Mateos

Goldschmidt

Miguel

et al. 2018

Hematological Oncology

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“…In subgroup analyses of ENDEAVOR, for patients receiving carfilzomib plus dexamethasone, median PFS was 8.6 months for patients with lenalidomide-refractory disease and not estimable in those who were not refractory to lenalidomide. In individuals receiving bortezomib plus dexamethasone, median PFS was 6.6 months for patients with lenalidomide-refractory disease and 11.2 months for those who were not refractory to lenalidomide (Moreau et al, 2016c). It must be noted that for both PIs efficacy was greater in patients who were not refractory to lenalidomide than in those with refractory disease.…”

Section: Imid-refractory Diseasementioning

confidence: 99%

A question of class: Treatment options for patients with relapsed and/or refractory multiple myeloma

Cook

Mateos

Suzan

et al. 2018

Critical Reviews in Oncology/Hematology

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A B S T R A C TMultiple classes of agent with distinct mechanisms of action are now available for the treatment of patients with relapsed and/or refractory multiple myeloma (RRMM), including immunomodulatory agents, proteasome inhibitors, histone deacetylase inhibitors and monoclonal antibodies. Additionally, several different drugs may be available within each agent class, each with their own specific efficacy and safety profile. This expansion of the treatment landscape has dramatically improved outcomes for patients. However, as the treatment options for RRMM become more complex, choosing the class of agent or combination of agents to use in the relapsed setting becomes increasingly challenging. Furthermore, treatment options for specific patient populations such as the elderly, those with high-risk cytogenetic abnormalities and those with refractory disease are yet to be defined in the current treatment landscape. When choosing an appropriate treatment approach, physicians must consider multiple criteria including both patient-related and disease-related factors. The aim should be to provide patientspecific treatment in order to gain a clinical benefit while minimizing toxicity. This review provides an overview of the mechanism of action and efficacy and safety profiles of each class of agent and of treatment regimens that combine different classes of agent, with a special focus on treating specific patient populations.

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“…62 Carfilzomib, ixazomib, and daratumumab combinations are superior whatever the number of lines (1-3). 59,68,69 c The prior use and results of IMIDs and PIs are becoming important issues. Patients with prior treatment are bortezomib-or lenalidomide-exposed; others are bortezomib-or lenalidomide-naive.…”

Section: 55mentioning

confidence: 99%

How I treat first relapse of myeloma

Harousseau

Attal

2017

Blood

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The standard treatment of relapsed multiple myeloma has been either lenalidomide-dexamethasone (RD) or bortezomib-dexamethasone (VD) but it is changing rapidly for 2 reasons. First, lenalidomide and bortezomib are currently used in frontline treatment and many patients become resistant to these agents early in the course of their disease. Second, 6 second-line new agents have been recently developed and offer new possibilities (pomalidomide, carfilzomib and ixazomib, panobinostat, elotuzumab, and daratumumab). Recent randomized studies have shown that triple combinations adding 1 of these new agents (except pomalidomide) to the RD or VD regimens were superior to the double combinations in terms of response rate and progression-free survival (PFS). Their place in the treatment of first relapse is discussed here. Among these agents, daratumumab is clearly a breakthrough and daratumumab-based combinations might become the preferred option in the near future. However, all of these drugs are expensive and are not available or affordable in all countries. We propose a decision algorithm for first relapse in fit patients with the objective of achieving the best PFS. The choice of salvage regimen is based on lenalidomide/bortezomib resistance, daratumumab availability, and cost. Autologous transplantation should be considered in younger patients if not used upfront.

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Impact of prior treatment on patients with relapsed multiple myeloma treated with carfilzomib and dexamethasone vs bortezomib and dexamethasone in the phase 3 ENDEAVOR study

Cited by 68 publications

References 19 publications

Carfilzomib in relapsed or refractory multiple myeloma patients with early or late relapse following prior therapy: A subgroup analysis of the randomized phase 3 ASPIRE and ENDEAVOR trials

Carfilzomib in relapsed or refractory multiple myeloma patients with early or late relapse following prior therapy: A subgroup analysis of the randomized phase 3 ASPIRE and ENDEAVOR trials

A question of class: Treatment options for patients with relapsed and/or refractory multiple myeloma

How I treat first relapse of myeloma

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