Elotuzumab, pomalidomide, and dexamethasone is a very well tolerated regimen associated with durable remission even in very advanced myeloma: a retrospective study from two academic centers

Abstract

Background The anti-SLAMF7 monoclonal antibody, elotuzumab (elo), plus lenalidomide (len) and dexamethasone (dex) is approved for relapsed/refractory MM in the U.S. and Europe. Recently, a small phase 2 study demonstrated an advantage in progression-free survival (PFS) for elo plus pomalidomide (pom)/dex compared to pom/dex alone and resulted in licensing of this novel triplet combination, but clinical experience is still limited. Purpose To analyze the efficacy and safety of elo/pom/dex in a "real world" cohort of patients with advanced MM, we queried the databases of the university hospitals of Würzburg and Vienna. Findings We identified 22 patients with a median number of five prior lines of therapy who received elo/pom/dex prior to licensing within an early access program. Patients received a median number of 5 four-week treatment cycles. Median PFS was 6.4 months with 12-month and 18-month PFS rates of 35% and 28%, respectively. The overall response rate was 50% and 64% of responding patients who achieved a longer PFS with elo/pom/dex compared to their most recent line of therapy. Objective responses were also seen in five patients who had been pretreated with pomalidomide. Low tumor burden was associated with improved PFS (13.5 months for patients with ISS stage I/II at study entry v 6.4 months for ISS III), although this difference did not reach statistical significance. No infusion-related reactions were reported. The most frequent grade 3/4 adverse events were neutropenia and pneumonia. Conclusion Elo/pom/dex is an active and well-tolerated regimen in highly advanced MM even after pretreatment with pomalidomide.

Advances in the Treatment of Relapsed and Refractory Multiple Myeloma in Patients with Renal Insufficiency: Novel Agents, Immunotherapies and Beyond

“…Median progression-free survival with elotuzumab plus pomalidomide and dexamethasone was 10.3 months and the overall response rate amounted to 53%, which alone demonstrates the superiority of this treatment over pomalidomide and dexamethasone (4.7 months in the group with pomalidomide plus dexamethasone, HR 0.54 (95% CI 0.34-0.86); p = 0.0080) [84]. Another study proved a median PFS of 6.4 months, with PRS rates after 12 and 18 months being similar to those reported in a current update of the ELOQUENT-3 study [85]. An adjustment of the elotuzumab and pomalidomide doses is not required in patients with severe renal insufficiency, including kidney disease in the end stage.…”

CARAMBA: a first-in-human clinical trial with SLAMF7 CAR-T cells prepared by virus-free Sleeping Beauty gene transfer to treat multiple myeloma

“…tEGFR is recognized by the medicinal antibody cetuximab and serves three purposes: (i) quantification of CAR-transduced cells during manufacturing and formulation, (ii) detection of CAR-transduced cells in patient blood, and (iii) CAR-T-cell depletion with therapeutic doses of cetuximab in case of severe toxicity [ 50 ]. The targeting domain of the CAR is derived from the medicinal anti-SLAMF7-antibody elotuzumab the safety and tolerability of which was shown previously [ 51 ].…”

Elotuzumab spares dendritic cell integrity and functionality

“…Recently, the results from the ELOQUENT3 study have been supported by real-world data, underlining again that neutropenia and pneumonia are serious side effects of this therapeutic regime (Hose et al 2021 ).…”

“…Recently, the results from the ELOQUENT3 study have been supported by real-world data, underlining again that neutropenia and pneumonia are serious side effects of this therapeutic regime (Hose et al 2021). MM patients have been described to be per se sevenfold more susceptible to develop infections compared to population controls (Girmenia et al 2019).…”