Phase II study of the c-MET inhibitor tivantinib (ARQ 197) in patients with relapsed or relapsed/refractory multiple myeloma

Muhamed Baljevic, Shadia Zaman, Veerabhadran Baladandayuthapani, Yan Heather Lin, Claudia Morales de Partovi, Zuzana Berkova, Behrang Amini, Sheeba K. Thomas, Jatin J. Shah, Donna M. Weber, Min Fu, Charles S. Cleeland, Xin Shelley Wang, Christine M. Stellrecht, Richard E. Davis, Varsha Gandhi, Robert Z. Orlowski

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The hepatocyte growth factor/c-MET pathway has been implicated in the pathobiology of multiple myeloma, and c-MET inhibitors induce myeloma cell apoptosis, suggesting that they could be useful clinically. We conducted a phase II study with the c-MET inhibitor tivantinib in patients with relapsed, or relapsed and refractory myeloma whose disease had progressed after one to four prior therapies. Tivantinib, 360 mg orally per dose, was administered twice daily continuously over a 4-week treatment cycle without a cap on the number of allowed cycles, barring undue toxicities or disease progression. Primary objectives were to determine the overall response rate and the toxicities of tivantinib in this patient population. Sixteen patients were enrolled in a two-stage design. Notable grade 3 and 4 hematological adverse events were limited to neutropenia in five and four patients, respectively. Nonhematological adverse events of grade 3 or higher included hypertension (in four patients); syncope, infection, and pain (two each); and fatigue, cough, and pulmonary embolism (one each). Four of 11 evaluable patients (36%) had stable disease as their best response, while the remainder showed disease progression. Overall, tivantinib as a single agent did not show promise for unselected relapsed/refractory myeloma patients. However, the ability to achieve stable disease does suggest that combination regimens incorporating targeted inhibitors in patients with c-MET pathway activation could be of interest.

Original languageEnglish (US)
Pages (from-to)977-985
Number of pages9
JournalAnnals of Hematology
Volume96
Issue number6
DOIs
StatePublished - Jun 1 2017

Fingerprint

Multiple Myeloma
Disease Progression
Aptitude
Hepatocyte Growth Factor
ARQ 197
Syncope
Neutropenia
Pulmonary Embolism
Cough
Fatigue
Apoptosis
Hypertension
Pain
Therapeutics
Infection
Population

Keywords

  • ARQ 197
  • Multiple myeloma
  • Relapsed
  • Tivantinib
  • c-MET

ASJC Scopus subject areas

  • Hematology

Cite this

Phase II study of the c-MET inhibitor tivantinib (ARQ 197) in patients with relapsed or relapsed/refractory multiple myeloma. / Baljevic, Muhamed; Zaman, Shadia; Baladandayuthapani, Veerabhadran; Lin, Yan Heather; de Partovi, Claudia Morales; Berkova, Zuzana; Amini, Behrang; Thomas, Sheeba K.; Shah, Jatin J.; Weber, Donna M.; Fu, Min; Cleeland, Charles S.; Wang, Xin Shelley; Stellrecht, Christine M.; Davis, Richard E.; Gandhi, Varsha; Orlowski, Robert Z.

In: Annals of Hematology, Vol. 96, No. 6, 01.06.2017, p. 977-985.

Research output: Contribution to journalArticle

Baljevic, M, Zaman, S, Baladandayuthapani, V, Lin, YH, de Partovi, CM, Berkova, Z, Amini, B, Thomas, SK, Shah, JJ, Weber, DM, Fu, M, Cleeland, CS, Wang, XS, Stellrecht, CM, Davis, RE, Gandhi, V & Orlowski, RZ 2017, 'Phase II study of the c-MET inhibitor tivantinib (ARQ 197) in patients with relapsed or relapsed/refractory multiple myeloma', Annals of Hematology, vol. 96, no. 6, pp. 977-985. https://doi.org/10.1007/s00277-017-2980-3
Baljevic, Muhamed ; Zaman, Shadia ; Baladandayuthapani, Veerabhadran ; Lin, Yan Heather ; de Partovi, Claudia Morales ; Berkova, Zuzana ; Amini, Behrang ; Thomas, Sheeba K. ; Shah, Jatin J. ; Weber, Donna M. ; Fu, Min ; Cleeland, Charles S. ; Wang, Xin Shelley ; Stellrecht, Christine M. ; Davis, Richard E. ; Gandhi, Varsha ; Orlowski, Robert Z. / Phase II study of the c-MET inhibitor tivantinib (ARQ 197) in patients with relapsed or relapsed/refractory multiple myeloma. In: Annals of Hematology. 2017 ; Vol. 96, No. 6. pp. 977-985.
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abstract = "The hepatocyte growth factor/c-MET pathway has been implicated in the pathobiology of multiple myeloma, and c-MET inhibitors induce myeloma cell apoptosis, suggesting that they could be useful clinically. We conducted a phase II study with the c-MET inhibitor tivantinib in patients with relapsed, or relapsed and refractory myeloma whose disease had progressed after one to four prior therapies. Tivantinib, 360 mg orally per dose, was administered twice daily continuously over a 4-week treatment cycle without a cap on the number of allowed cycles, barring undue toxicities or disease progression. Primary objectives were to determine the overall response rate and the toxicities of tivantinib in this patient population. Sixteen patients were enrolled in a two-stage design. Notable grade 3 and 4 hematological adverse events were limited to neutropenia in five and four patients, respectively. Nonhematological adverse events of grade 3 or higher included hypertension (in four patients); syncope, infection, and pain (two each); and fatigue, cough, and pulmonary embolism (one each). Four of 11 evaluable patients (36{\%}) had stable disease as their best response, while the remainder showed disease progression. Overall, tivantinib as a single agent did not show promise for unselected relapsed/refractory myeloma patients. However, the ability to achieve stable disease does suggest that combination regimens incorporating targeted inhibitors in patients with c-MET pathway activation could be of interest.",
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AU - Zaman, Shadia

AU - Baladandayuthapani, Veerabhadran

AU - Lin, Yan Heather

AU - de Partovi, Claudia Morales

AU - Berkova, Zuzana

AU - Amini, Behrang

AU - Thomas, Sheeba K.

AU - Shah, Jatin J.

AU - Weber, Donna M.

AU - Fu, Min

AU - Cleeland, Charles S.

AU - Wang, Xin Shelley

AU - Stellrecht, Christine M.

AU - Davis, Richard E.

AU - Gandhi, Varsha

AU - Orlowski, Robert Z.

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