Clinical challenges associated with bortezomib therapy in multiple myeloma and Waldenströms Macroglobulinemia

Rapid development of the small molecule proteasome inhibitor bortezomib has yielded important clinical benefit for patients with multiple myeloma. Early phase clinical trials suggest the agent has similar efficacy in Waldenströms Macroglobulinemia. Optimization of bortezomib-based therapy, though, requires an understanding of the various challenges associated with use of the drug. This review highlights the rationale for bortezomib therapy in patients with multiple myeloma and Waldenströms Macroglobulinemia, mechanisms of bortezomib resistance, important therapy-related side effects, and new directions for the use of proteasome inhibitors in these disorders.

[1]  M. Dimopoulos,et al.  Treatment of light chain deposition disease with bortezomib and dexamethasone , 2009, Haematologica.

[2]  Michael L. Wang,et al.  Initial Results of PX-171-004, An Open-Label, Single-Arm, Phase II Study of Carfilzomib (CFZ) in Patients with Relapsed Myeloma (MM) , 2008 .

[3]  S. Jagannath,et al.  Initial Results of PX-171-003, An Open-Label, Single-Arm, Phase II Studyof Carfilzomib (CFZ) in Patients with Relapsed and Refractory Multiple Myeloma (MM) , 2008 .

[4]  M. Dimopoulos,et al.  Superior Outcomes Associated with Complete Response: Analysis of the Phase III VISTA Study of Bortezomib Plus Melphalan–Prednisone Versus Melphalan–Prednisone , 2008 .

[5]  M. Kersten,et al.  First Analysis of HOVON-65/GMMG-HD4 Randomized Phase III Trial Comparing Bortezomib, Adriamycine, Dexamethasone (PAD) Vs VAD as Induction Treatment Prior to High Dose Melphalan (HDM) in Patients with Newly Diagnosed Multiple Myeloma (MM) , 2008 .

[6]  M. Baccarani,et al.  Superior Complete Response Rate and Progression-Free Survival after Autologous Transplantation with up-Front Velcade-Thalidomide- Dexamethasone Compared with Thalidomide-Dexamethasone in Newly Diagnosed Multiple Myeloma , 2008 .

[7]  S. Amara.  Oral Glutamine for the Prevention of Chemotherapy-Induced Peripheral Neuropathy , 2008, The Annals of pharmacotherapy.

[8]  G. Peters,et al.  Molecular basis of bortezomib resistance: proteasome subunit beta5 (PSMB5) gene mutation and overexpression of PSMB5 protein. , 2008, Blood.

[9]  A. Argyriou,et al.  Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature. , 2008, Blood.

[10]  Krishna R. Kalari,et al.  Proteasome β Subunit Pharmacogenomics: Gene Resequencing and Functional Genomics , 2008, Clinical Cancer Research.

[11]  D. Chauhan,et al.  Dual targeting of the proteasome regulates survival and homing in Waldenstrom macroglobulinemia. , 2008, Blood.

[12]  Wolfgang Grisold,et al.  Chemotherapy‐induced neuropathy , 2008, Journal of the peripheral nervous system : JPNS.

[13]  K. Dellagi,et al.  Single autologous stem-cell transplantation followed by maintenance therapy with thalidomide is superior to double autologous transplantation in multiple myeloma: results of a multicenter randomized clinical trial. , 2008, Blood.

[14]  P. Hawkins,et al.  Efficacy of bortezomib in systemic AL amyloidosis with relapsed/refractory clonal disease , 2008, Haematologica.

[15]  M. Mohty,et al.  VELCADE/Dexamethasone (Vel/D) Versus VAD as Induction Treatment Prior to Autologous Stem Cell Transplantion (ASCT) in Newly Diagnosed Multiple Myeloma (MM): Updated Results of the IFM 2005/01 Trial. , 2007 .

[16]  D. Esseltine,et al.  Lenalidomide, Bortezomib, and Dexamethasone (Rev/Vel/Dex) in Patients with Relapsed or Relapsed/Refractory Multiple Myeloma (MM): Preliminary Results of a Phase II Study. , 2007 .

[17]  D. Esseltine,et al.  Lenalidomide, Bortezomib, and Dexamethasone (Rev/Vel/Dex) as Front-Line Therapy for Patients with Multiple Myeloma (MM): Preliminary Results of a Phase 1/2 Study. , 2007 .

[18]  Anthony Boral,et al.  Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. , 2007, Blood.

[19]  M. Dimopoulos,et al.  Treatment of light chain (AL) amyloidosis with the combination of bortezomib and dexamethasone , 2007, Haematologica.

[20]  G. Cavaletti,et al.  Bortezomib-induced peripheral neurotoxicity: still far from a painless gain , 2007, Haematologica.

[21]  B. Barlogie,et al.  Incorporating bortezomib into upfront treatment for multiple myeloma: early results of total therapy 3 , 2007, British journal of haematology.

[22]  S. Demo,et al.  Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. , 2007, Cancer research.

[23]  M. Baccarani,et al.  Prospective, randomized study of single compared with double autologous stem-cell transplantation for multiple myeloma: Bologna 96 clinical study. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  R. Advani,et al.  Multicenter Clinical Trial of Bortezomib in Relapsed/Refractory Waldenstrom's Macroglobulinemia: Results of WMCTG Trial 03-248 , 2007, Clinical Cancer Research.

[25]  E. Eisenhauer,et al.  Bortezomib is active in patients with untreated or relapsed Waldenstrom's macroglobulinemia: a phase II study of the National Cancer Institute of Canada Clinical Trials Group. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  Jin-Hwang Liu,et al.  Oral glutamine is effective for preventing oxaliplatin-induced neuropathy in colorectal cancer patients. , 2007, The oncologist.

[27]  N. Munshi,et al.  High-dose therapy with single autologous transplantation versus chemotherapy for newly diagnosed multiple myeloma: A systematic review and meta-analysis of randomized controlled trials. , 2007, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[28]  A. O. Bayrak,et al.  PYRIDOXINE AND PYRIDOSTIGMINE TREATMENT IN VINCRISTINE-INDUCED NEUROPATHY , 2007, Pediatric hematology and oncology.

[29]  Anthony Boral,et al.  Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib. , 2006, Blood.

[30]  D. Reece,et al.  Bortezomib therapy response is independent of cytogenetic abnormalities in relapsed/refractory multiple myeloma. , 2006, Leukemia research.

[31]  S. Jagannath,et al.  Lenalidomide Plus Bortezomib (Rev-Vel) in Relapsed and/or Refractory Multiple Myeloma (MM): Final Results of a Multicenter Phase 1 Trial. , 2006 .

[32]  Serge Leyvraz,et al.  Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. , 2006, Blood.

[33]  C. Heussel,et al.  Effects of bortezomib on pro‐inflammatory cytokine levels and transfusion dependency in a patient with multicentric Castleman Disease , 2006, British journal of haematology.

[34]  D. Esseltine,et al.  Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[35]  John Crowley,et al.  Thalidomide and hematopoietic-cell transplantation for multiple myeloma. , 2006, The New England journal of medicine.

[36]  E. Terpos,et al.  No evidence of mutations of the PSMB5 (beta-5 subunit of proteasome) in a case of myeloma with clinical resistance to Bortezomib. , 2006, Leukemia research.

[37]  D. Esseltine,et al.  Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma. , 2005, Blood.

[38]  J. S. San Miguel,et al.  High-dose therapy intensification compared with continued standard chemotherapy in multiple myeloma patients responding to the initial chemotherapy: long-term results from a prospective randomized trial from the Spanish cooperative group PETHEMA. , 2005, Blood.

[39]  D. Esseltine,et al.  Clinical factors predictive of outcome with bortezomib in patients with relapsed, refractory multiple myeloma. , 2005, Blood.

[40]  Hiroshi Yasui,et al.  A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib. , 2005, Cancer cell.

[41]  D. Esseltine,et al.  PAD combination therapy (PS‐341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma , 2005, British journal of haematology.

[42]  G. Morgan,et al.  Preclinical evaluation of the proteasome inhibitor bortezomib in cancer therapy , 2005, Cancer Cell International.

[43]  D. Esseltine,et al.  Phase 1 trial of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with advanced hematologic malignancies. , 2005, Blood.

[44]  J. Tchinda,et al.  Bortezomib in combination with dexamethasone for relapsed multiple myeloma. , 2005, Leukemia research.

[45]  N. Cherny.  The pharmacologic management of cancer pain. , 2004, Oncology.

[46]  D. Esseltine,et al.  A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma , 2004, British journal of haematology.

[47]  R. Bataille,et al.  Single versus double autologous stem-cell transplantation for multiple myeloma. , 2003, The New England journal of medicine.

[48]  C. N. Coleman,et al.  CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. , 2003, Seminars in radiation oncology.

[49]  Bart Barlogie,et al.  A phase 2 study of bortezomib in relapsed, refractory myeloma. , 2003, The New England journal of medicine.

[50]  N. Munshi,et al.  Molecular sequelae of histone deacetylase inhibition in human malignant B cells. , 2003, Blood.

[51]  K. Anderson,et al.  The proteasome inhibitor PS-341 potentiates sensitivity of multiple myeloma cells to conventional chemotherapeutic agents: therapeutic applications. , 2003, Blood.

[52]  M. Borad,et al.  The proteasome inhibitor PS-341 markedly enhances sensitivity of multiple myeloma tumor cells to chemotherapeutic agents. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[53]  N. Munshi,et al.  Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. , 2002, Blood.

[54]  K. Kraemer,et al.  Molecular aspects of lipoic acid in the prevention of diabetes complications. , 2001, Nutrition.

[55]  R. Champlin,et al.  Impact of complete remission with intensive therapy in patients with responsive multiple myeloma , 2001, Bone Marrow Transplantation.

[56]  Z Chen,et al.  Novel proteasome inhibitor PS-341 inhibits activation of nuclear factor-kappa B, cell survival, tumor growth, and angiogenesis in squamous cell carcinoma. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[57]  B. Barlogie,et al.  Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma. , 1997, Blood.

[58]  J. Rossi,et al.  A Prospective, Randomized Trial of Autologous Bone Marrow Transplantation and Chemotherapy in Multiple Myeloma , 1996 .

[59]  E. McFadden,et al.  Toxicity and response criteria of the Eastern Cooperative Oncology Group , 1982, American journal of clinical oncology.

[60]  T E Walsh,et al.  Reporting results. , 1969, Archives of otolaryngology.

[61]  A. Satterfield,et al.  TREATMENT , 1924, California and western medicine.

[62]  M. Gordon.  Bortezomib plus Melphalan and Prednisone for Initial Treatment of Multiple Myeloma , 2009 .

[63]  M. Gordon.  Randomized Phase III Study of Pegylated Liposomal Doxorubicin Plus Bortezomib Compared With Bortezomib Alone in Relapsed or Refractory Multiple Myeloma: Combination Therapy Improves Time to Progression , 2008 .

[64]  D. De Grandis.  Acetyl-L-carnitine for the treatment of chemotherapy-induced peripheral neuropathy: a short review. , 2007, CNS drugs.

[65]  P. Sonneveld,et al.  Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials , 2007, Leukemia.

[66]  M. Gordon.  Bortezomib or High-Dose Dexamethasone for Relapsed Multiple Myeloma , 2006 .

[67]  M. Dimopoulos,et al.  Treatment of relapsed or refractory Waldenström's macroglobulinemia with bortezomib. , 2005, Haematologica.

[68]  D. Cella,et al.  Quality of life evaluation in chronic illness across cultures: The Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System and its use in India , 2000 .

[69]  J. Rossi,et al.  A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. , 1996, The New England journal of medicine.

[70]  A. Miller,et al.  Reporting results of cancer treatment , 1981, Cancer.