Carfilzomib, lenalidomide, and dexamethasone in patients with relapsed multiple myeloma categorised by age: secondary analysis from the phase 3 ASPIRE study

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Summary

A primary analysis of the ASPIRE study found that the addition of carfilzomib to lenalidomide and dexamethasone (carfilzomib group) significantly improved progression‐free survival ( PFS) compared with lenalidomide and dexamethasone alone (control group) in patients with relapsed multiple myeloma ( RMM). This post hoc analysis examined outcomes from ASPIRE in patients categorised by age. In the carfilzomib group, 103/396 patients were ≥70 years old, and in the control group, 115/396 patients were ≥70 years old. Median PFS for patients <70 years old was 28·6 months for the carfilzomib group versus 17·6 months for the control group [hazard ratio ( HR), 0·701]. Median PFS for patients ≥70 years old was 23·8 months for the carfilzomib group versus 16·0 months for the control group ( HR, 0·753). For patients <70 years the overall response rate ( ORR) was 86·0% (carfilzomib group) and 66·9% (control group); for patients ≥70 years old the ORR was 90·3% (carfilzomib group) and 66·1% (control group). Within the carfilzomib group, grade ≥3 cardiovascular adverse events occurred more frequently among patients ≥70 years old compared with patients <70 years old. Carfilzomib‐lenalidomide‐dexamethasone has a favourable benefit‐risk profile for patients with RMM, including elderly patients ≥70 years old. Trial Registration : clinicaltrials.gov identifier: NCT01080391.

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Most cited references 22

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A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma.

Andrzej Jakubowiak, Dominik Dytfeld, Kent Griffith … (2012)

This phase 1/2 study in patients with newly diagnosed multiple myeloma (N = 53) assessed CRd--carfilzomib (20, 27, or 36 mg/m2, days 1, 2, 8, 9, 15, 16 and 1, 2, 15, 16 after cycle 8), lenalidomide (25 mg/d, days 1-21), and weekly dexamethasone (40/20 mg cycles 1-4/5+)--in 28-day cycles. After cycle 4, transplantation-eligible candidates underwent stem cell collection (SCC) then continued CRd with the option of transplantation. The maximum planned dose level (carfilzomib 36 mg/m2) was expanded in phase 2 (n = 36). Thirty-five patients underwent SCC, 7 proceeded to transplantation, and the remainder resumed CRd. Grade 3/4 toxicities included hypophosphatemia (25%), hyperglycemia (23%), anemia (21%), thrombocytopenia (17%), and neutropenia (17%); peripheral neuropathy was limited to grade 1/2 (23%). Most patients did not require dose modifications. After a median of 12 cycles (range, 1-25), 62% (N = 53) achieved at least near-complete response (CR) and 42% stringent CR. Responses were rapid and improved during treatment. In 36 patients completing 8 or more cycles, 78% reached at least near CR and 61% stringent CR. With median follow-up of 13 months (range, 4-25 months), 24-month progression-free survival estimate was 92%. CRd was well tolerated with exceptional response rates. This study is registered at http://www.clinicaltrials.gov as NCT01029054.

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Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial.

Philippe Casassus, Claire Mathiot, Gaelle Guillerm … (2009)

Until recently, melphalan and prednisone were the standards of care in elderly patients with multiple myeloma. The addition of thalidomide to this combination demonstrated a survival benefit for patients age 65 to 75 years. This randomized, placebo-controlled, phase III trial investigated the efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed myeloma. Between April 2002 and December 2006, 232 previously untreated patients with myeloma, age 75 years or older, were enrolled and 229 were randomly assigned to treatment. All patients received melphalan (0.2 mg/kg/d) plus prednisone (2 mg/kg/d) for 12 courses (day 1 to 4) every 6 weeks. Patients were randomly assigned to receive 100 mg/d of oral thalidomide (n = 113) or placebo (n = 116), continuously for 72 weeks. The primary end point was overall survival. After a median follow-up of 47.5 months, overall survival was significantly longer in patients who received melphalan and prednisone plus thalidomide compared with those who received melphalan and prednisone plus placebo (median, 44.0 v 29.1 months; P = .028). Progression-free survival was significantly prolonged in the melphalan and prednisone plus thalidomide group (median, 24.1 v 18.5 months; P = .001). Two adverse events were significantly increased in the melphalan and prednisone plus thalidomide group: grade 2 to 4 peripheral neuropathy (20% v 5% in the melphalan and prednisone plus placebo group; P < .001) and grade 3 to 4 neutropenia (23% v 9%; P = .003). This trial confirms the superiority of the combination melphalan and prednisone plus thalidomide over melphalan and prednisone alone for prolonging survival in very elderly patients with newly diagnosed myeloma. Toxicity was acceptable.

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Population-based assessment of hospitalizations for toxicity from chemotherapy in older women with breast cancer.

Deborah S. Goodwin, Cynthia Osborne, X. Du (2002)

There are no population-based data on hospitalization rate for toxicity from breast cancer chemotherapy, and even large clinical trials often do not report this information. Medicare data, linked to the Surveillance, Epidemiology, and End-Results (SEER) tumor registries, are now used to assess rates of hospitalization for chemotherapy-related toxicity in a population-based setting. A total of 35,060 women diagnosed with stages I through IV breast cancer aged >or= 65 from 1991 through 1996 were identified from the SEER-Medicare linked program and studied. Patients were defined as being hospitalized for adverse effects of chemotherapy if there was a Medicare inpatient claim for neutropenia, fever, thrombocytopenia, or adverse effect of systemic therapy less than 7 months after diagnosis of breast cancer. More than 9% of women with breast cancer who received chemotherapy were admitted with the diagnosis of neutropenia, fever, thrombocytopenia, or adverse effect of systemic therapy, compared with 0.5% of women with breast cancer who did not receive chemotherapy. The rates for stage I to IV were 6.3%, 8.1%, 12.3%, and 13.2% in those treated with chemotherapy, and 0.4%, 0.6%, 0.7%, and 1.5% in women not treated with chemotherapy. The hospitalization rates for adverse effects increased significantly with comorbidity score and varied more than two-fold across the nine SEER areas but did not vary by age. Use of anthracycline-containing chemotherapy agents was associated with greater odds of these toxicities (eg, odds ratio, 2.53 for neutropenia; 95% confidence interval, 1.97 to 3.26). This study demonstrated the feasibility of using Medicare data to assess rates of hospitalization for serious toxicity associated with cancer chemotherapy. Rates in actual practice were higher than those reported in clinical trials and did not vary by age.

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Author and article information

Contributors

Meletios A. Dimopoulos: mdimop@med.uoa.gr

Journal

Journal ID (nlm-ta): Br J Haematol

Journal ID (iso-abbrev): Br. J. Haematol

Journal ID (doi): 10.1111/(ISSN)1365-2141

Journal ID (publisher-id): BJH

Title: British Journal of Haematology

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Print): 0007-1048

ISSN (Electronic): 1365-2141

Publication date (Electronic): 17 February 2017

Publication date (Print): May 2017

Volume: 177

Issue: 3 ( doiID: 10.1111/bjh.2017.177.issue-3 )

Pages: 404-413

Affiliations

[ ¹ ]National and Kapodistrian University of Athens AthensGreece

[ ² ]Mayo Clinic Scottsdale AZUSA

[ ³ ] St István and St Laszlo Hospital 3rd Dept. of Internal MedicineSemmelweis University BudapestHungary

[ ⁴ ] First Faculty of MedicineCharles University in Prague PragueCzech Republic

[ ⁵ ] Institut Català d'OncologiaHospital Germans Trias i Pujol BarcelonaSpain

[ ⁶ ] University Hospital Ostrava and Faculty of MedicineUniversity of Ostrava OstravaCzech Republic

[ ⁷ ]Hospital Clínic de Barcelona BarcelonaSpain

[ ⁸ ]John Theurer Cancer Center at Hackensack University Hackensack NJUSA

[ ⁹ ]Queen Joanna University Hospital SofiaBulgaria

[ ¹⁰ ]Haematology Clinic University Multiprofile Hospital for Active Treatment PlovdivBulgaria

[ ¹¹ ] Department of HaematologyMór Kaposi Teaching Hospital KaposvárHungary

[ ¹² ] Haematological DepartmentFirst Republican Clinical Hospital of Udmurtia IzhevskRussia

[ ¹³ ]Weill Cornell Medical College New York NYUSA

[ ¹⁴ ]University of Chicago Medical Center Chicago ILUSA

[ ¹⁵ ]Clinica Universidad de Navarra CIMA IDISNA PamplonaSpain

[ ¹⁶ ] Wilhelminen Cancer Research InstituteWilhelminenspital ViennaAustria

[ ¹⁷ ]University of Torino TorinoItaly

[ ¹⁸ ]Onyx Pharmaceuticals, Inc. an Amgen subsidiary South San Francisco CAUSA

[ ¹⁹ ]University of Nantes NantesFrance

Author notes

[*] [* ] Correspondence: Meletios A. Dimopoulos, M.D., National and Kapodistrian University of Athens Alexandra Hospital, 80 Vas Sofias Avenue, Athens 11528, Greece.

E‐mail: mdimop@ 123456med.uoa.gr

Author information

Péter Rajnics http://orcid.org/0000-0003-3985-5826

Article

Publisher ID: BJH14549

DOI: 10.1111/bjh.14549

PMC ID: 5412871

PubMed ID: 28211560

SO-VID: 97e2d045-a934-4b89-ac13-e44134e9667b

License:

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

History

Date received : 22 September 2016

Date accepted : 01 December 2016

Page count

Figures: 2, Tables: 3, Pages: 10, Words: 7521

Funding

Funded by: Onyx Pharmaceuticals, Inc

Custom metadata

source-schema-version-number 2.0

component-id bjh14549

cover-date May 2017

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:5.0.9 mode:remove_FC converted:02.05.2017

ScienceOpen disciplines: Hematology

Keywords: carfilzomib,lenalidomide,dexamethasone,relapsed multiple myeloma,clinical trial

Data availability:

ScienceOpen disciplines: Hematology

Keywords: carfilzomib, lenalidomide, dexamethasone, relapsed multiple myeloma, clinical trial

Carfilzomib, lenalidomide, and dexamethasone in patients with relapsed multiple myeloma categorised by age: secondary analysis from the phase 3 ASPIRE study

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Most cited references 22

A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma.

Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial.

Population-based assessment of hospitalizations for toxicity from chemotherapy in older women with breast cancer.

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