A majority of patients with multiple myeloma (MM) relapse after therapy, and the duration of remission decreases with each line of therapy.1 Novel agents, including proteasome inhibitors (PIs) and immunomodulatory agents (IMIDs), have improved outcomes for patients with MM.2 However, treatment options are limited for patients who become refractory to PIs and IMIDs. The CD38 inhibitor daratumumab has demonstrated rapid, deep, and durable responses in patients with relapsed/refractory (R/R) MM, both as a single agent and in combination with the IMID, lenalidomide, or the PI, bortezomib.3–5 Daratumumab was also well tolerated, with manageable adverse events.

The phase III POLLUX study found improved out- comes with the combination of daratumumab, lenalidomide, and dexamethasone (DRd) over lenalidomide and dexamethasone (Rd) in patients with R/R MM4, while the phase III CASTOR study showed a similar benefit for daratumumab, bortezo- mib, and dexamethasone (DVd) over bortezomib and dexamethasone (Vd).5

Daratumumab has been approved as monotherapy for patients with heavily pretreated R/R MM by the Food and Drug Administration (FDA), the European Medicines Agency, Health Canada, Mexico, and Singapore. The FDA, in part due to data from the POLLUX and CASTOR studies, has also approved daratumumab in combination with standard of care regimens in patients with R/R MM after at least one prior therapy.

New Evidence reported on the results of five studies, presented at the 2016 American Society of Hematology (ASH) Annual Meeting, which reaffirmed the efficacy and safety of daratumumab in patients with R/R MM:

  • Updated results from the POLLUX study demonstrated improved outcomes with DRd over Rd in patients with R/R MM and 1–3 prior lines of treatment. Benefits with DRd were seen regardless of prior lenalidomide treatment, refractoriness to bortezomib, or cytogenetic profile. (Moreau P, et al. ASH 2016:489)
  • An additional analysis of the POLLUX study found that patients who received DRd experienced deeper responses than those who received Rd, regardless of the risk status or refractoriness to prior treatment. (Usmani SZ, et al. ASH 2016:1151)
  • An updated analysis of the CASTOR study reaf- firmed the superiority of the combination of DVd over Vd in patients with R/R MM. The superiority of DVd over Vd was observed regardless of prior lines of therapy, with the greatest benefit observed in patients with one prior line of therapy. (Mateos MV, et al. ASH 2016:1150)
  • Results from the Early Access Treatment Protocol (EAP), which provided patients with early access to daratumumab, showed that patients with R/R MM who received daratumumab experienced similar adverse events as previously reported while main- taining quality of life. (Chari A, et al. ASH 2016:2133)
  • A subanalysis of the EAP provided evidence that premedication with montelukast may mitigate infusion-related reactions associated with the first infusion of daratumumab. (Chari A, et al. ASH2016:2142)

References: 1. Kumar SK, Lee JH, Lahuerta JJ, et al. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: A multicenter international myeloma working group study. Leukemia 2012;26:149–57. 2. Rajkumar SV. Myeloma today: Disease definitions and treatment advances. Am J Hematol 2016;92:90–100. 3. Lonial S, Weiss BM, Usmani SZ, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet 2016;387:1551–60. 4. Dimopoulos MA, Oriol A, Nahi H, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med 2016;375:1319–31. 5. Palumbo A, Chanan-Khan A, Weisel K, et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med 2016;375:754–66.

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Contributors

Dr. Berinstein
Neil Berinstein, MD, FRCPC, ABIM
Dr. Neil Berinstein earned his premedical degree and medical doctorate from the University of Manitoba and received further specialty and research training at the University of Toronto and Stanford University. Dr. Berinstein currently holds multiple academic and professional positions, including Professor in the Department of Medicine at the University of Toronto, and is an active staff member of the Hematology Oncology Site Group in the Odette Cancer Program at the Sunnybrook Health Sciences Centre. He is currently the Director of Translational Research at the Ontario Institute for Cancer Research. Dr. Berinstein specializes in the management and research of patients with lymphoproliferative disorders, including non-Hodgkin lymphoma, chronic lymphocytic leukemia, Hodgkin lymphoma, and myeloma.

Dr. Cheson
Bruce D. Cheson, MD, FACP, FAAS, FASCO
Dr. Bruce Cheson completed his internship and residency in Internal Medicine at the University of Virginia Hospitals and then a clinical and research fellowship in Hematology at New England Medical Center Hospital. He is former Editor-in-Chief of Clinical Advances in Hematology and Oncology and Clinical Lymphoma, Leukemia and Myeloma, and a former Associate Editor of the Journal of Clinical Oncology. From 2002 to 2006, he was on the Oncologic Drug Advisory Committee to the U.S. Food and Drug Administration. He is past-Chair of the Lymphoma Committee of the Cancer and Leukemia Group B/Alliance, the Scientific Advisory Board of the Lymphoma Research Foundation, and the American Joint Committee on Cancer (AJCC) Subcommittee on Lymphoma. Currently, Dr. Cheson is Professor of Medicine, Head of Hematology, and Deputy Chief of Hematology-Oncology at Georgetown University Hospital, Lombardi Comprehensive Cancer Center. Dr. Cheson’s clinical interests focus on the development and evaluation of new therapeutic approaches for hematologic malignancies.

Dr. Connors
Joseph Connors, MD, FRCPC
Dr. Joseph Connors earned his medical degree from Yale University. He completed his residency training in Internal Medicine and chief residency at the University of North Carolina in Chapel Hill. Prior to completing his Medical Oncology Fellowship at Stanford University, he worked at the Indian Health Service in Alaska for two years. In 1981, he accepted a position in Medical Oncology at the BC Cancer Agency. He has been a member of the Faculty of Medicine at the University of British Columbia since that time, reaching the position of Clinical Professor in 1997. At present, he is a Clinical Professor in the Department of Medicine, Division of Medical Oncology, at the University of British Columbia and the Chair of the Lymphoma Tumour Group for the BC Cancer Agency. Dr. Connors’ clinical activities and research efforts are focused in the area of lymphoid cancers. He is best known for his clinical investigations into the treatment of Hodgkin lymphoma, non-Hodgkin lymphoma, chronic lymphocytic leukemia, and multiple myeloma.

Dr. LeBlanc
Richard LeBlanc, MD, FRCPC
Dr. Richard LeBlanc is a hematologist and medical oncologist at Hôpital Maisonneuve-Rosemont in Montreal, Quebec. He is also a Clinical Assistant Professor of Medicine at the University of Montreal. Dr. LeBlanc obtained his medical degree at Laval University and is certified in Internal Medicine, Hematology, and Medical Oncology. He worked as a research fellow at the Dana Farber Cancer Institute in Boston from 2000 to 2002. Dr. LeBlanc was recruited by Hôpital Maisonneuve-Rosemont to help improve medical care, research, and teaching in multiple myeloma. Dr. LeBlanc holds the Myeloma Canada Chair at the University of Montreal. He is the Director of the Myeloma Cell Bank at Hôpital Maisonneuve-Rosemont, which is affiliated with the Quebec Leukemia Cell Bank. He is also the Medical Director of the Clinical Immunology Laboratory at Hôpital Maisonneuve-Rosemont. Finally, Dr. LeBlanc is a member of the Scientific Advisory Board of Myeloma Canada.

Dr. Owen
Carolyn Owen, MD, FRCPC
Dr. Carolyn Owen completed postgraduate training in internal medicine and hematology at the University of Ottawa and the University of British Columbia, respectively, followed by a research fellowship in molecular genetics at Barts and the London School of Medicine and Dentistry in London, U.K. Her research focused on familial myelodysplasia and acute myeloid leukemia. She is currently an Assistant Professor at the Foothills Medical Centre and Tom Baker Cancer Centre, University of Calgary, and her clinical interests are low-grade lymphoma and chronic lymphocytic leukemia. She is also the local principal investigator in Calgary for several clinical trials in these areas.

Dr. Peters
Anthea Peters, MD, FRCPC
Dr. Anthea Peters obtained her medical degree from the University of Saskatchewan in 2006. She then completed her residencies in Internal Medicine at the University of Alberta and in Hematology at the University of Calgary. Dr. Peters joined the Division of Hematology at the University of Alberta as a Clinical Scholar in July 2011. Her main area of interest is in lymphoma.