A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma

David S. Siegel, Thomas Martin, Michael Wang, Ravi Vij, Andrzej J. Jakubowiak, Sagar Lonial, Suzanne Trudel, Vishal Kukreti, Nizar Bahlis, Melissa Alsina, Asher A Chanan Khan, Francis Buadi, Frederic J. Reu, George Somlo, Jeffrey Zonder, Kevin Song, Alexander Keith Stewart, Edward Stadtmauer, Lori Kunkel, Sandra WearAlvin F. Wong, Robert Z. Orlowski, Sundar Jagannath

Research output: Contribution to journalArticle

464 Citations (Scopus)

Abstract

Carfilzomib is a next-generation, selective proteasome inhibitor being evaluated for the treatment of relapsed and refractory multiple myeloma. In this open-label, single-arm phase 2 study (PX-171-003- A1), patients received single-agent carfilzomib 20 mg/m2 intravenously twice weekly for 3 of 4 weeks in cycle 1, then 27 mg/m2 for ≤ 12 cycles. The primary endpoint was overall response rate (≥ partial response). Secondary endpoints included clinical benefit response rate (≥ minimal response), duration of response, progression-free survival, overall survival, and safety. A total of 266 patients were evaluable for safety, 257 for efficacy; 95% were refractory to their last therapy; 80% were refractory or intolerant to both bortezomib and lenalidomide. Patients had median of 5 prior lines of therapy, including bortezomib, lenalidomide, and thalidomide. Overall response rate was 23.7% with median duration of response of 7.8 months. Median overall survival was 15.6 months. Adverse events (AEs) were manageable without cumulative toxicities. Common AEs were fatigue (49%), anemia (46%), nausea (45%), and thrombocytopenia (39%). Thirtythree patients (12.4%) experienced peripheral neuropathy, primarily grades 1 or 2. Thirty-three patients (12.4%) withdrew because of an AE. Durable responses and an acceptable tolerability profile in this heavily pretreated population demonstrate the potential of carfilzomib to offer meaningful clinical benefit. This trial was registered at www.clinicaltrials.gov as #NCT00511238.

Original languageEnglish (US)
Pages (from-to)2817-2825
Number of pages9
JournalBlood
Volume120
Issue number14
DOIs
StatePublished - Oct 4 2012

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Multiple Myeloma
Refractory materials
Proteasome Inhibitors
Thalidomide
Toxicity
Labels
Safety
Fatigue of materials
Survival
Peripheral Nervous System Diseases
Thrombocytopenia
Nausea
Disease-Free Survival
Fatigue
Anemia
Therapeutics
carfilzomib
lenalidomide
Bortezomib
Population

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Siegel, D. S., Martin, T., Wang, M., Vij, R., Jakubowiak, A. J., Lonial, S., ... Jagannath, S. (2012). A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood, 120(14), 2817-2825. https://doi.org/10.1182/blood-2012-05-425934

A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. / Siegel, David S.; Martin, Thomas; Wang, Michael; Vij, Ravi; Jakubowiak, Andrzej J.; Lonial, Sagar; Trudel, Suzanne; Kukreti, Vishal; Bahlis, Nizar; Alsina, Melissa; Chanan Khan, Asher A; Buadi, Francis; Reu, Frederic J.; Somlo, George; Zonder, Jeffrey; Song, Kevin; Stewart, Alexander Keith; Stadtmauer, Edward; Kunkel, Lori; Wear, Sandra; Wong, Alvin F.; Orlowski, Robert Z.; Jagannath, Sundar.

In: Blood, Vol. 120, No. 14, 04.10.2012, p. 2817-2825.

Research output: Contribution to journalArticle

Siegel, DS, Martin, T, Wang, M, Vij, R, Jakubowiak, AJ, Lonial, S, Trudel, S, Kukreti, V, Bahlis, N, Alsina, M, Chanan Khan, AA, Buadi, F, Reu, FJ, Somlo, G, Zonder, J, Song, K, Stewart, AK, Stadtmauer, E, Kunkel, L, Wear, S, Wong, AF, Orlowski, RZ & Jagannath, S 2012, 'A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma', Blood, vol. 120, no. 14, pp. 2817-2825. https://doi.org/10.1182/blood-2012-05-425934
Siegel, David S. ; Martin, Thomas ; Wang, Michael ; Vij, Ravi ; Jakubowiak, Andrzej J. ; Lonial, Sagar ; Trudel, Suzanne ; Kukreti, Vishal ; Bahlis, Nizar ; Alsina, Melissa ; Chanan Khan, Asher A ; Buadi, Francis ; Reu, Frederic J. ; Somlo, George ; Zonder, Jeffrey ; Song, Kevin ; Stewart, Alexander Keith ; Stadtmauer, Edward ; Kunkel, Lori ; Wear, Sandra ; Wong, Alvin F. ; Orlowski, Robert Z. ; Jagannath, Sundar. / A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. In: Blood. 2012 ; Vol. 120, No. 14. pp. 2817-2825.
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AU - Martin, Thomas

AU - Wang, Michael

AU - Vij, Ravi

AU - Jakubowiak, Andrzej J.

AU - Lonial, Sagar

AU - Trudel, Suzanne

AU - Kukreti, Vishal

AU - Bahlis, Nizar

AU - Alsina, Melissa

AU - Chanan Khan, Asher A

AU - Buadi, Francis

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AU - Somlo, George

AU - Zonder, Jeffrey

AU - Song, Kevin

AU - Stewart, Alexander Keith

AU - Stadtmauer, Edward

AU - Kunkel, Lori

AU - Wear, Sandra

AU - Wong, Alvin F.

AU - Orlowski, Robert Z.

AU - Jagannath, Sundar

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N2 - Carfilzomib is a next-generation, selective proteasome inhibitor being evaluated for the treatment of relapsed and refractory multiple myeloma. In this open-label, single-arm phase 2 study (PX-171-003- A1), patients received single-agent carfilzomib 20 mg/m2 intravenously twice weekly for 3 of 4 weeks in cycle 1, then 27 mg/m2 for ≤ 12 cycles. The primary endpoint was overall response rate (≥ partial response). Secondary endpoints included clinical benefit response rate (≥ minimal response), duration of response, progression-free survival, overall survival, and safety. A total of 266 patients were evaluable for safety, 257 for efficacy; 95% were refractory to their last therapy; 80% were refractory or intolerant to both bortezomib and lenalidomide. Patients had median of 5 prior lines of therapy, including bortezomib, lenalidomide, and thalidomide. Overall response rate was 23.7% with median duration of response of 7.8 months. Median overall survival was 15.6 months. Adverse events (AEs) were manageable without cumulative toxicities. Common AEs were fatigue (49%), anemia (46%), nausea (45%), and thrombocytopenia (39%). Thirtythree patients (12.4%) experienced peripheral neuropathy, primarily grades 1 or 2. Thirty-three patients (12.4%) withdrew because of an AE. Durable responses and an acceptable tolerability profile in this heavily pretreated population demonstrate the potential of carfilzomib to offer meaningful clinical benefit. This trial was registered at www.clinicaltrials.gov as #NCT00511238.

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