Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended 3-year follow-up of a multicenter, retrospective clinical experience with 319 cases outside of controlled clinical trials.

The combination of elotuzumab, lenalidomide, and dexamethasone (EloRd) enhanced the clinical benefit over Rd with a manageable toxicity profile in the ELOQUENT-2 trial, leading to its approval in relapsed/refractory multiple myeloma (RRMM). The present study is a 3-year follow-up update of a previously published Italian real-life RRMM cohort of patients treated with EloRd. This revised analysis entered 319 RRMM patients accrued in 41 Italian centers. After a median follow-up of 36 months (range 6-55), 236 patients experienced disease progression or died. Median progression-free survival (PFS) and overall survival (OS) were 18.4 and 34 months, respectively. The updated multivariate analyses showed a significant reduction of PFS and OS benefit magnitude only in cases with International Staging System stage III. Major adverse events included grade 3/4 neutropenia (18.5%), anemia (15.4%), lymphocytopenia (12.5%), and thrombocytopenia (10.7%), while infection rates and pneumonia were 33.9% and 18.9%, respectively. No new safety signals with longer follow-up have been observed. Of 319 patients, 245 (76.7%) reached at least a partial remission. A significantly lower response rate was found in patients previously exposed to lenalidomide. In conclusion, our study confirms that EloRd is a safe and effective regimen for RRMM patients, maintaining benefits across multiple unfavorable subgroups.

Is re-challenge still an option as salvage therapy in multiple myeloma? The case of REal-life BOrtezomib re-Use as secoND treatment for relapsed patients exposed frontline to bortezomib-based therapies (the REBOUND Study).

Therapeutic re-challenge is currently a debated issue in the field of multiple myeloma (MM), given the recent availability of several new drugs and combinations. However, very few specific evidences are available about bortezomib re-use at first relapse. This multicenter, observational, retrospective study enrolled 134 MM patients with significant response after bortezomib-based frontline regimens and who had received a first salvage treatment containing bortezomib at relapse. The overall response rate was 71%, including 40% partial responses, 24% very good partial responses, and 7% complete responses. Re-treatment was well-tolerated, with no significant new or unexpected toxicities observed. The median duration of second progression-free survival (PFS) was 15 months, while median PFS2 was 55 months. With a median follow-up of 56 months, overall survival was 94 months for the entire series, without significant differences between patients undergoing or not undergoing transplant procedures. This real-life survey indicates that re-treatment including bortezomib as a first salvage therapy could be still considered in MM patients achieving durable response after initial exposure to bortezomib.

Combined use of free light chain and heavy/light chain ratios allow diagnosis and monitoring of patients with monoclonal gammopathies: Experience of a single institute, with three exemplar case reports.

Monoclonal gammopathies are characterized by serum monoclonal component (MC) plus an intact immunoglobulin and a free light chain (FLC), or a combination of both. The measurement of FLC with Freelite® is the standard practice recommended by International Myeloma Working Group guidelines. Recently, Hevylite® heavy/light chains (HLC) assays were introduced to specifically target junctional epitopes between the heavy and light chains of intact immunoglobulins, allowing the independent quantification of the involved (MC) and uninvolved (polyclonal immunoglobulin background) HLC isotype. Between January 2012 and March 2014, 90 patients were examined: 49 multiple myeloma (MM), 6 smoldering MM (SMM) and 35 monoclonal gammopathy of undetermined significance (MGUS). Of these 90 patients, 300 samples were collected at different times. The diagnostic and monitoring contribution of Hevylite A and G assays was assessed in all 90 patients examined. Additionally, 3 representative cases were selected. The Hevylite absolute values and ratio demonstrated high sensitivity and specificity with respect to serum protein electrophoresis and serum immunofixation. The combined use of Hevylite A and G with Freelite was particularly useful in dubious cases with more than one MC or with co-migrating components, as well as in the course of monitoring to assess the independent change of FLC and HLC, possibly reflecting the presence of clonal heterogeneity in the cohort. From this study, it can be concluded that FLC and HLC are independent, useful markers to monitor the MC and to assess with greater specificity and sensitivity the effect of therapy, thereby providing clinical support. Further studies are required to assess the prognostic potential of Hevylite in MGUS and SMM.