Elotuzumab Added to Lenalidomide and Dexamethasone Fails to Improve PFS in Multiple Myeloma

Article

The combination of elotuzumab plus lenalidomide and dexamethasone did not demonstrate a statistically significant improvement in progression-free survival compared with lenalidomide and dexamethasone alone in newly diagnosed patients with multiple myeloma who are transplant ineligible, missing the primary end point of the phase III ELOQUENT-1 trial.<br /> &nbsp;

Meletios A. Dimopoulos, MD

Meletios A. Dimopoulos, MD

Meletios A. Dimopoulos, MD

The combination of elotuzumab (Empliciti) plus lenalidomide (Revlimid) and dexamethasone (ERd) did not demonstrate a statistically significant improvement in progression-free survival (PFS) compared with lenalidomide and dexamethasone alone in newly diagnosed patients with multiple myeloma who are transplant ineligible, missing the primary end point of the phase III ELOQUENT-1 trial (NCT01335399), Bristol Myers Squibb announced in a press release.

Following a full evaluation of ELOQUENT-1, the trial data will be presented at a future medical meeting. Thus far, the company, which is co-developing elotuzumab with AbbVie, has shared that the safety profile of ERd was consistent with previous reports.

&ldquo;Multiple myeloma is an aggressive disease characterized by relapse and the likelihood to be refractory to several therapies,&rdquo; investigator Meletios A. Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at Kapodistrian University of Athens School of Medicine, said in the press release. &ldquo;While the elotuzumab, lenalidomide and dexamethasone combination was unable to show a benefit in patients with newly diagnosed multiple myeloma at this time, it remains an important treatment option in the relapsed/refractory setting.&rdquo;

The secondary end points of the randomized, open-label trial included objective response rate (ORR) and overall survival (OS).

The randomized, open-label trial included approximately 750 patients. In the comparator arm, patients received oral lenalidomide, 25 mg, on days 1 through 21 and oral dexamethasone, 40 mg, on days 1, 8, 15, and 22, in 28-day cycles. In the experimental arm, elotuzumab was administered at 10 mg/kg intravenously on days 1, 8, 15, and 22 of the first 2 cycles followed by on days 1 and 15 of cycles 3 through 18 and 20 mg/kg on day 1 of cycle 19 and beyond. Dexamethasone was administered at 8 mg intravenous and 28 mg orally when given with elotuzumab. &nbsp;

To be eligible for ELOQUENT-1, patients could not have received any prior systemic anti-myeloma therapy, were required to have measurable disease, and could not be candidates for high-dose therapy plus stem cell transplantation (SCT) because of age (&ge;65 years) or comorbid conditions. The study excluded patients with non-secretory, oligo-secretory, or free light-chain only myeloma; smoldering multiple myeloma; Monoclonal Gammopathy of Undetermined Significance; active plasma cell leukemia; and known immunodeficiency virus, infection, or active hepatitis A, B, or C.

&ldquo;While we are disappointed that the ELOQUENT-1 trial did not meet its primary end point in these previously untreated, transplant-ineligible patients, the Empliciti, Revlimid, and dexamethasone combination remains a standard treatment for patients with relapsed/refractory multiple myeloma, providing the potential for improved survival in this population of patients who are in need of additional treatment options,&rdquo; said Noah Berkowitz, MD, PhD, senior vice president, Global Clinical Development, Hematology, Bristol Myers Squibb.

Although ELOQUENT-1 did not show promise in terms of PFS, a phase III study (ELOQUENT-2, NCT01239797), met its primary efficacy end points of PFS, ORR, and its secondary end point OS, according to data published inCancerin 2018.2Based on ELOQUENT-2, another phase III study was launched, and quality-of-life results were announced at the 2019 American Society of Hematology (ASH) Annual Meeting.3In ELOQUENT-3, lenalidomide is replaced by pomalidomide (Pomalyst) and the regimen did not impair health-related quality of life in the study subjects. The triplet regimen from the ELOQUENT-3 trial was approved by the FDA in November 2018 for use in the relapsed/refractory setting for patients who have received 2 or more prior therapies, including lenalidomide and a proteasome inhibitor.

The differences in results between these 3 studies may suggest that the combination of a monoclonal antibody, chemotherapy, and a corticosteroid serves better in the relapsed/refractory setting than the newly diagnosed, previously untreated setting for patients with multiple myeloma.

References

  1. Bristol Myers Squibb Reports Primary results of ELOQUENT-1 study evaluating empliciti (elotuzumab) plus revlimid (lenalidomide) and dexamethasone in patients with newly diagnosed, untreated multiple myeloma [news release]. Princeton, NJ: Bristol Myers Squibb; March 9, 2020.https://bit.ly/2Q2DPdr. Accessed March 10, 2020.
  2. Dimopoulos MA, KLonial S, Betts KA, et al. Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended 4‐year follow‐up and analysis of relative progression‐free survival from the randomized ELOQUENT‐2 trial.Cancer. 2018;20. doi: 10.1002/cncr.31680.
  3. Weisel K, Paner A, Engelhardt M, et al. Impact of elotuzumab plus pomalidomide and dexamethasone on health-related quality of life in patients with relapsed/refractory multiple myeloma enrolled in the ELOQUENT-3 study.Blood. 2019;134(suppl_1). doi: 10.1182/blood-2019-122232.
Recent Videos
Related Content