Choice of Myeloma Posters
Niels Abildgaard, et al.
This ongoing, prospective, non-interventional study in pts with RRMM continues to demonstrate that POM-based Tx is generally well tolerated in the real-world setting and that the safety profile is not impacted by the Tx administered immediately before starting a POM-based Tx. Of all pts included in this trial, more pts were treated with LEN immediately before starting POM than any other drug. This analysis shows that AEs are almost similar in pts treated with LEN or BORT or both or any other drug immediately before starting POM Tx. In addition, the reported VTEs, PNs, and SPMs were generally low in all subgroups. Updated data will be presented at the meeting
Adeela Mushtaq, et al.
From results of pooled analysis, we can infer that triplet combinations of Pom yield almost double response rates (pooled ORR 61.9%) when compared to dual combination of Pom-LoDex (pooled ORR 35.7%). Among three drug combinations, Bort-Pom-LoDex (pooled ORR 83.5%) and CFZ-Pom-LoDex (pooled ORR 77.1%) seem to produce better outcomes. Our study provides useful insight into relative efficacy of various Pom regimens for treatment of RRMM patients. Several trials involving various MoAbs like nivolumab, daratumumab, elotuzumab, isatuximab and pembrolizumab in combination with Pom-LoDex are currently ongoing. Pomalidomide has an acceptable safety profile. Most common treatment emergent adverse events were myelotoxicity and infections that can be effectively managed with supportive care and dose modifications.
1992 Longer Term Follow up of the Â Randomized Phase III Trial SWOG S0777: Bortezomib, Lenalidomide and Dexamethasone Vs. Lenalidomide and Dexamethasone in Patients (Pts) with Previously Untreated Multiple Myeloma without an Intent for Immediate Autologous Stem Cell Transplant (ASCT)
Brian GM Durie, et al.
The addition of bortezomib to lenalidomide dexamethasone for induction therapy in previously untreated myeloma results in a statistically significant and clinically meaningful improvement in PFS as well as better OS with follow up of 7 years. VRd had an acceptable safety and tolerability profile and continues to represent an appropriate standard of care irrespective of age.
Christine I Chen, et al.
Enrollment is ongoing to evaluate once weekly selinexor in combination with Pd , (SPd). This all-oral SPd combination has clinical activity with an ORR 55% in pom-naive pts with heavily pretreated MM compared to previously published data of 30% ORR for Pd alone. Similarly, the PFS on SPd is 10.3 months vs. <4 months for Pd alone. No unexpected adverse events were noted. Phase 1 dose escalation of the combination of SPd is ongoing to define the optimal RP2D.
Sundar Jagannath, et al.
EPd was associated with a median PFS of 11.1 mo and ORR of 51% in pts with RRMM. Safety was consistent with prior reports of elotuzumab and pom, with no new safety signals. These data, coupled with findings from the randomized ELOQUENT-3 study, support EPd as a new, effective treatment option for pts with RRMM.
Study support: BMS. Medical writing: Adam Gill, Caudex, funded by BMS
3274 Cyclophosphamide, Pomalidomide and Dexamethasone Significantly Improves Response over Poma/Dex in Relapsed/Refractory Myeloma Patients Previously Treated with Cyclophosphamide Combination Therapy – Initial Results of the Randomised Multicentre Mukseven Trial
James Croft, et al.
The combination of cyclophosphamide, pomalidomide and dexamethasone significantly increases response rates and depth of response compared to pomalidomide and dexamethasone in RRMM patients, even those that have already been exposed to cyclophosphamide combination therapy in previous lines of therapy. Primary endpoint PFS data for CPd vs. Pd will be presented at the conference. Analyses of outcomes in the context of molecular profiles are ongoing and will be presented at the conference.
2008 Real-World Outcomes with Bortezomib-Containing Regimens and Lenalidomide Plus Dexamethasone for the Treatment of Transplant Ineligible MM Patients: A Multi-Institutional Report from the National Myeloma Canada Research Network (MCRN) Database
Victor Jimenez-Zepeda, et al.
1) OS was not significantly different in patients treated with either a bortezomib-containing triplet that includes an alkylator + steroid or continuous Ld. 2) The BCR triplets and Ld were more efficacious than the bortezomib + steroid doublet (VD/VP) for both OS and PFS although, the small sample size and adverse factors, such as frailty and comorbidities, may have influenced the findings. 3) The results in the real-world setting, i.e., a median PFS in the range of 1.5-2 years and median OS of 4.5-5.5 years, confirm triplet-based BCRs and Ld as current valid standards of care for frontline therapy in TIMM. 5) This study confirms the utility of a large comprehensive national database to benchmark current results for comparison with newer regimens as they are introduced into the Canadian therapeutic landscape.
David S Siegel, et al.
LEN-refractory pts with RRMM are in need of effective Tx options. MM-014 is the first prospective clinical trial to investigate a POM-based doublet or triplet regimen immediately after LEN-based Tx failure. In the context of a relatively short follow-up, the 9-mo PFS rate (86.3%) is promising. The ORR (77.7%) was higher than that previously reported with this triplet combination in heavily pre-treated pts with RRMM (≥ 2 prior lines [median, 4]; ORR, 60%), and the rate of grade 3/4 neutropenia in the present study was lower (61.6% vs 77%). These updated results from cohort B continue to demonstrate that POM + LoDEX + DARA is safe and effective following first- or second-line LEN-based Tx failure and further support earlier use of POM-based Tx in pts with RRMM
3278 Pomalidomide + Bortezomib + Low-Dose Dexamethasone Vs Bortezomib + Low-Dose Dexamethasone As Second-Line Treatment in Patients with Lenalidomide-Pretreated Multiple Myeloma: A Subgroup Analysis of the Phase 3 Optimismm Trial
Meletios A Dimopoulos, et al.
To date, OPTIMISMM is the only phase 3 trial to address Tx of pts with RRMM following LEN exposure in early lines and the first to report data in LEN-refractory pts after first relapse. PVd reduced the risk of progression and death by 45% and 46% vs Vd in LEN-refractory and -nonrefractory pts, respectively. Further, in both subgroups, 2L Tx with PVd significantly improved ORR and led to deeper responses compared with Vd. AEs with PVd therapy were generally consistent with the known AEs of POM, BORT, and DEX. These data further demonstrate that PVd is effective and tolerable in pts for whom LEN is no longer a Tx option, including LEN-refractory pts, supporting its use as 2L therapy in RRMM.
Mark Katz, et al.
Pomalidomide, bortezomib and dexamethasone exert synergistic anti-proliferative effects on tumor cells. Despite inhibiting proteasomal activity, bortezomib does not antagonize pomalidomide-mediated degradation of Cereblon substrates Aiolos, Ikaros and ZFP91 when used at therapeutically relevant concentrations. Pulsing experiments provide the advantage of mimicking bortezomib dosing regimens; under these conditions, pomalidomide-mediated degradation of substrates was still observed. In immune cells, the PV combination has an overall positive impact on T-cell proliferation despite inhibitory activity of single agent bortezomib. Our results suggest that in combination, pomalidomide can overcome the immunosuppressive effects of bortezomib, when bortezomib is used at therapeutic levels.
James Croft, et al.
We demonstrate for the first time in a randomised trial using systematic longitudinal immune profiling that addition of cyclophosphamide to pomalidomide and dexamethasone is significantly associated with altered T-cell profiles and an increased proportion of activated T-cells. MUKseven clinical endpoint data are reported separately, with improved response rates observed for CPd vs. Pd. Correlation of immune profiles with clinical outcomes and tumour genetics will be presented at the conference when PFS outcome data will be mature.