Silver Spring, MD (Press Release) – On No­vem­ber 30, 2015, the U. S. Food and Drug Admin­istra­tion approved elotuzumab (EMPLICITI, Bristol-Myers Squibb Com­pany) in com­bi­na­tion with lena­lido­mide and dexa­metha­sone for the treat­ment of patients with mul­ti­ple myeloma who have re­ceived one to three prior ther­a­pies.

Elotuzumab is a mono­clonal anti­body directed against Signaling Lymphocyte Activation Molecule Family 7 (SLAMF7). SLAMF7 is present on myeloma cells and is also present on natural killer cells.

The ap­prov­al was based on a multi­center, ran­dom­ized, open-label, con­trolled trial eval­u­ating pro­gres­sion-free sur­vival (PFS) and over­all re­sponse rate (ORR) in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma who had re­ceived 1 to 3 prior lines of ther­apy. A total of 646 patients were ran­dom­ized (1:1) to re­ceive elotuzumab in com­bi­na­tion with lena­lido­mide and dexa­metha­sone (n=321) or lena­lido­mide plus dexa­metha­sone alone (n=325). Patients con­tinued treat­ment until dis­ease pro­gres­sion or the devel­op­ment of un­ac­cept­able toxicity.

The trial dem­onstrated a statistically sig­nif­i­cant im­prove­ment in both PFS and ORR, the trial’s co-primary end­points. The median PFS in the elotuzumab-containing arm was 19.4 months and 14.9 months in the lena­lido­mide plus dexa­metha­sone alone arm (hazard ratio 0.70, 95% CI: 0.57, 0.85; p = 0.0004). The ORR in the elotuzumab-containing arm was 78.5% (95% CI: 73.6, 82.9) com­pared to 65.5% (95% CI: 60.1, 70.7) in the lena­lido­mide plus dexa­metha­sone alone arm (p=0.0002).

The safety data reflect exposure in 318 patients to elotuzumab in com­bi­na­tion with lena­lido­mide and dexa­metha­sone and 317 patients to lena­lido­mide plus dexa­metha­sone. The most common adverse reac­tions (greater than or equal to 20%), with an in­­creased rate in the elotuzumab arm com­pared to the con­trol arm, were fatigue, diarrhea, pyrexia, con­sti­pa­tion, cough, periph­eral neu­rop­athy, nasopharyngitis, upper res­pira­tory tract in­fec­tion, de­creased appetite, and pneu­monia.

Other im­por­tant adverse reac­tions in­clude in­fusion reac­tions, in­fec­tions, sec­ond pri­mary malig­nan­cies, hepato­tox­ic­ity, and inter­fer­ence with deter­mi­na­tion of com­plete re­sponse. As elotuzumab is an IgG kappa mono­clonal anti­body, it can be detected in the serum pro­tein electrophoresis and immuno­fix­a­tion assays used to assess re­sponse.

Serious adverse events oc­curred in 65.4% of patients in the elotuzumab-containing arm com­pared to 56.5% in the lena­lido­mide plus dexa­metha­sone alone arm. The most common serious adverse reac­tions were pneu­monia, pyrexia, res­pira­tory tract in­fec­tion, anemia, pul­mo­nary embolism, and acute renal failure.

The rec­om­mended dose and schedule for elotuzumab is 10 mg/kg in­tra­venously every week for the first two cycles and every 2 weeks, there­after, until dis­ease pro­gres­sion or unacceptable toxicity with lena­lido­mide 25 mg daily orally on days 1 through 21. Dexa­metha­sone is admin­istered as follows: In weeks with elotuzumab in­fusion, dexa­metha­sone is to be admin­istered in divided doses, 8 mg in­tra­venously prior to in­fusion and 28 mg orally; in weeks without elotuzumab in­fusion, dexa­metha­sone is to be admin­istered 40 mg orally. Pre-medication with an H1 blocker, H2 blocker, and acet­amin­o­phen should be admin­istered prior to elotuzumab in­fusion.

Elotuzumab is being approved prior to the Prescription Drug User Fee Act (PDUFA) goal date of Feb­ru­ary 29, 2016. This appli­ca­tion was granted priority review and had break­­through ther­apy desig­na­tion. A description of these expedited pro­grams is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, avail­able at:

http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf

Full pre­scrib­ing in­­for­ma­tion is avail­able at:

http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/761035s000lbl.pdf

Healthcare professionals should report all serious adverse events sus­pected to be asso­ci­ated with the use of any med­i­cine and device to FDA’s MedWatch Reporting System by com­plet­ing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

Source: Food and Drug Admin­istra­tion.