Daratumumab and Len/Dex -- 'Standout' Myeloma Combo

Roxanne Nelson, BSN, RN

October 06, 2016

Daratumumab (Darzalex, Janssen Biotech) represents a "landmark advance" in myeloma therapy and will likely be incorporated into the treatment of all stages of the disease over the next several years, comment experts writing in an editorial in the October 6 issue of the New England Journal of Medicine.

That said, the "challenge will be to prevent unnecessary use, since it will be hard to isolate the effect of daratumumab when it is combined with multiple other active agents," say the editorialists, S. Vincent Rajkumar, MD, and Robert A. Kyle, MD, both from the Mayo Clinic, Rochester, Minnesota.

Daratumumab is the first monoclonal antibody approved for the treatment of myeloma. It received approval from the US Food and Drug Administration last year for use in patients who have received at least three previous lines of therapy. It targets the CD38 antigen, which is present on nearly all myeloma cells.

The editorial was prompted by the publication of results from the POLLUX trial, which show that the addition of daratumumab to lenalidomide (Revlimid, Celgene) and dexamethasone (multiple brands) significantly lengthened progression-free survival among patients with relapsed or refractory multiple myeloma.

The rate of progression-free survival at 12 months was 83.2% for patients who received daratumumab, compared with 60.1% in the control group.

Patients in the daratumumab group also had a significantly higher rate of overall response and complete response.

"This combination (daratumumab, lenalidomide, and dexamethasome) is the preferred treatment for patients who have failed frontline therapy and who are not resistant to lenalidomide," said lead author Meletios-Athanassios Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine, Greece.

He presented the results from POLLUX during a presidential symposium at the European Hematology Association (EHA) 2016 Congress. Some weeks earlier, the results from the companion study CASTOR were presented during a plenary session at the annual meeting at the American Society of Clinical Oncology.

The CASTOR study showed that daratumumab combined with bortezomib (Velcade, Millennium) and dexamethasone significantly increased progression-free survival in patients with relapsed or refractory disease, and that triplet combination was declared to be a "new standard of care" for relapsed myeloma.

"CASTOR and POLLUX trials included patients with different disease characteristics," Dr Dimopoulos told Medscape Medical News. "It appears that daratumumab may become a backbone treatment for the management of patients with relapsed myeloma," he said at the time.

Combo Is "Clear Standout"

In their editorial, Dr Rajkumar and Dr Kyle say that the combination of daratumumab-lenalidomide-dexamethasone "is the clear standout."

"The magnitude of benefit is impressive, and the regimen is relatively easy to administer, especially after the first 6 months of therapy," they write.

"It is therefore our treatment of choice for first relapse in patients whose disease is not refractory to lenalidomide," they note, adding that for patients whose conditions have become refractory to lenalidomide, "a regimen of daratumumab-bortezomib-dexamethasone becomes a major option given the results of the CASTOR trial, although the older regimen of bortezomib-cyclophosphamide-dexamethasone is a reasonable alternative."

The authors emphasize that all three of the new regimens recently studied are active and should be considered in the treatment of each subsequent relapse. "Given the chronic relapsing course of myeloma, the most pressing questions revolve around the appropriate sequence in which these regimens are used, rather than picking winners and losers or excluding a regimen from consideration," they write.

"It will be important for future randomized trials to compare the various triplet regimens so that we can make more informed decisions," the editorialist conclude.

The POLLUX and CASTRO studies received funding from Janssen, manufacturer of daratumumab. Dr Dimopoulos has received fees for serving on advisory boards for Janssen, Celgene, Amgen, and Novartis and grant support from Janssen. Several coauthors also report relationships with industry, as noted in the article. Dr Rajkumar has disclosed no relevant financial relationships. Dr Kyle has received fees from Celgene, Bristol-Myers Squibb, Onyx Pharmaceuticals (Amgen), Pharmacyclics, Novartis, Merck, and Aeterna Zentaris (Keryx) outside the submitted work.

N Engl J Med. 2016;375:1319-1331, 1390-1392. Abstract, Editorial


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.