Data presented at the International Myeloma Society (IMS) annual meeting held September 27–30 in Athens, Greece, focused on 3 main topics: (1) the use of newer agents, (2) optimizing outcomes, and (3) the use of minimal residual disease (MRD) measurements to predict long-term outcome for patients or to potentially stop maintenance therapy.
In a study evaluating 2 vs 4 years of monthly intravenous ZOL, 192 symptomatic NDMM patients were randomized after 2 years ZOL to either 2 additional years of monthly IV ZOL or observation. The 2 additional years of ZOL were significantly superior in protecting against progressive bone disease (PBD): 8 cases were reported in the ZOL arm and 18 cases in the observational arm (HR: 0.38, 95% CI [0.17-0.88], P=0.024). In addition, there was no statistically significant difference in either osteonecrosis of the jaw (ONJ) incidence or OS between the 2 groups. According to the researchers, 79% of patients had bone involvement at diagnosis and 59% experienced bone pain. ZOL may help prevent PBD but is associated with ONJ, particularly when administered over a longer duration or with greater potency.
The final OS analysis of the OPTIMISMM trial comparing PVd vs Vd alone in patients with lenalidomide-refractory RRMM was reported. This randomized open-label phase 3 trial showed a nonsignificant trend towards improved OS with PVd (35.6 vs 31.6 months, respectively). During the study, 71% vs 70% died in the PVd and Vd groups, respectively. However, PFS was significantly improved with PVd versus Vd (22.1 vs 16.9 months; HR [95% CI], 0.77 [0.64–0.94]; P=.008). Time to treatment failure was also longer with PVd versus Vd (8.8 vs 4.6 months). The most common TEAEs with PVd were neutropenia (54%), peripheral sensory neuropathy (48%), and thrombocytopenia (40%); with Vd, the most common TEAEs were thrombocytopenia (39%), peripheral sensory neuropathy (38%), and diarrhea (31%). Peripheral neuropathy was the most common TEAE that resulted in discontinuation (PVd, 11%; Vd, 8%). According to the researchers, these data support the use of PVd as an effective treatment option in patients with RRMM.
The GMMG-CONCEPT trial evaluated the quadruplet isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in both transplant-eligible (TE) and ineligible (TNE) patients with newly diagnosed high-risk MM (HRMM), defined International Staging System (ISS) stage 2 or 3 and HRCA such as del17p, t(4;14), t(14;16), or >3 copies 1q21 (amp1q21). Results presented at IMS indicated substantial MRD negativity after consolidation, with rates of 67.7% for TE patients and 54.2% for TNE patients. The current analysis includes 127 TE and 26 TNE patients with sustained MRD negativity and PFS. After a median follow-up of 40 months for TE patients and 33 months for TNE patients, the median PFS had not yet been reached in either study arm. Exploratory analyses revealed promising 1-year and 2-year PFS rates for both groups. Additional subgroup analyses showed that patients with elevated lactate dehydrogenase (LDH) or ≥2 HRCAs or del17p were least likely to reach MRD negativity and had shortened PFS. The researchers reported that Isa-KRd induces high rates of sustained MRD negativity in newly diagnosed HRMM, translating to a median PFS that was not yet reached. The results of this study are now published and can be found here.
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This educational activity is supported by educational grants from AbbVie Inc., Bristol Myers Squibb, and GSK, and sponsorship from Legend Biotech USA Inc.
