Vorinostat

Vorinostat, a histone deacetylase (HDAC) inhibitor, already received FDA approval in 2006 for the treatment of patients with cutaneous T-cell lymphoma. Numerous studies are evaluating vorinostat in various combinations, such as with lenalidomide plus or minus dexamethasone, with carfilzomib, lenalidomide, and dexamethasone, and in conjunction with bortezomib, for relapsed/refractory myeloma in phase 1, 2, and 3 studies.11-13

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This is the only drug mentioned in this article that is being evaluated in patients with newly diagnosed multiple myeloma, including a phase 3 trial assessing the combination of thalidomide, lenalidomide, bortezomib, and vorinostat, and in combination with bortezomib.14,15

“Vorinostat is in the same class of drugs as the recently approved panobinostat,” Dr Manasanch told Cancer Therapy Advisor. “It’s always good to have a new drug in the same class given that there may be some pharmacokinetic and tolerability differences. Further studies are needed to delineate the precise role of vorinostat in newly diagnosed and relapsed/refractory myeloma.

CAR T-cell Therapy

Another therapy worth noting is chimeric antigen receptor (CAR) T-cell therapy. Preliminary results of a phase 1 trial presented at the American Society of Hematology 57th Annual Meeting & Exposition showed a partial response that lasted 2 weeks in 1 patient, a very good partial response in 1 patient, responses of stable disease in 7 patients, a stringent complete remission after 2 months in 1 patient, and a complete response after 4 weeks in 1 patient. The findings underscore the strong anti-myeloma activity of a CAR targeting B-cell maturation antigen (BCMA); however, this was a small study that only included 11 very heavily pretreated patients with advanced multiple myeloma.16

“Although still in early stages, CAR T-cell therapy is very promising. Clinical trials evaluating safety and efficacy of this new form of therapy should be a priority,” said Dr Manasanch.

Editor’s Note: This article was updated April 4, 2016 to include the most recent scientific data.

Reference

  1. Phase 2b open-label single-arm study of selinexor & dexamethasone in patients exposed to bortezomib, carfilzomib, lenalidomide and pomalidomide (STORM). ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/study/NCT02336815. November 9, 2015. Accessed March 11, 2016.
  2. Phase 1b/2 study of selinexor (KPT-330) in combination w/ backbone treatments for relapsed/refractory multiple myeloma (STOMP). ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/study/NCT02343042. January 29, 2016. Accessed March 11, 2016.
  3. Selinexor, carfilzomib, and dexamethasone in treating patients with relapsed or refractory multiple myeloma (SINE). ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/study/NCT02199665?term=selinexor&rank=9. January 28, 2016. Accessed March 11, 2016.
  4. Jakubowiak A, Jasielec J, Rosenbaum CA, et al. Phase 1 MMRC trial of selinexor, carfilzomib, and dexamethasone in relapsed and relapsed/refractory multiple myeloma [abstract]. Blood. 2015; 126(23):4223-4223.
  5. Triphase Accelerator Corporation announces phase 1 study results with marizomib in combination with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma [news release]. San Diego, CA: Triphase. September 26, 2015. http://triphaseco.com/wp-content/uploads/2015/09/MRZ-107-Study-IMW-Press-Release-09223015_FINAL.pdf. Accessed March 11, 2016.
  6. Phase 1/2 clinical trial of NPI-0052 in patients with relapsed or relapsed/refractory multiple myeloma. ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/NCT00461045. December 20, 2014. Accessed February March 11, 2016.
  7. Harrison SJ, Catley L, Price T, et al. Phase 1 clinical trial of marizomib (MRZ, NPI-0052) in patients with advanced malignancies including multiple myeloma: study NPI-0052-102 (NCT00629473) final results. Clin Lymphoma Myeloma Leuk. 2015. 15;3:e269.
  8. Aplidin – dexamethasone in relapsed/refractory myeloma (ADMYRE). ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/study/NCT01102426. June 11, 2015. Accessed March 11, 2016.
  9. Study of plitidepsin (Aplidin®) in combination with bortezomib and dexamethasone in patients with multiple myeloma. ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/study/NCT02100657. July 23, 2015. Accessed February March 11, 2016.
  10. Aplidin® shows positive results in pivotal Phase III clinical trial for multiple myeloma [news release]. Madrid, Spain: Pharma Mar; March 31, 2016. https://www.pharmamar.com/wp-content/uploads/2016/03/PR_Positive-Results_ADMYRE.pdf. Accessed April 4, 2016.
  11. Vorinostat and lenalidomide after autologous stem cell transplant in treating patients with multiple myeloma. ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/NCT00729118. September 8, 2015. Accessed March 11, 2016.
  12. A study of carfilzomib, lenalidomide, vorinostat, and dexamethasone in relapsed and/or refractory multiple myeloma (QUAD). ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/NCT01297764. August 20, 2015. Accessed March 11, 2016.
  13. Vorinostat, lenalinomide and dexamethasone in multiple myeloma refractory to previous lenalinomide containing regimens (RZD). ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/NCT01502085. August 21, 2015. Accessed March 11, 2016.
  14. Study of vorinostat (MK-0683) an HDAC inhibitor, or placebo in combination with bortezomib in patients with multiple myeloma (MK-0683-088 AMN). ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/NCT00773747. August 20, 2015. Accessed March 11, 2016.
  15. Use of thalidomide, lenalidomide, bortezomib and vorinostat in the initial treatment of newly diagnosed multiple myeloma patients (Myeloma XI). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01554852. March 19, 2012. Accessed March 11, 2016.
  16. Abbas S, Shi V, Wang M, et al. Remissions of multiple myeloma during a first-in-humans clinical trial of T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor [abstract]. Blood. 2015; 126(23):LBA-1.

Topics:

Hematologic Cancers Multiple Myeloma