Several oral presentations at this year’s American Society of Hematology (ASH) Annual Meeting & Exposition highlighted encouraging outcomes in the treatment of smoldering multiple myeloma (SMM), newly diagnosed MM (NDMM), and relapsed/refractory MM (RRMM). Presentations included updated data on bispecific antibodies (bsAbs) and chimeric antigen receptor T (CAR T)–cell therapy, as well as several novel agents in development.
The use of the bsAb teclistamab in patients with high-risk SMM was evaluated as part of the Immuno-PRISM trial, which examined whether bsAb therapy provided greater benefit in SMM than RRMM patients due to SMM patients having a more intact immune system and lower disease burden. Patients (n=12) received teclistamab alone or lenalidomide and dexamethasone. Teclistamab was associated with grade ≥3 hematologic toxicities, including neutropenia in 4 patients and thrombocytopenia in 1. Grade ≥3 non-hematologic toxicities included an increase in alanine transaminase (ALT) in 3 patients and pancreatitis in 1. Infections of any grade occurred in 9 patients, with one grade 3 case of sinusitis in 1 patient. Cytokine release syndrome (CRS) occurred in 75% of patients, mostly grade 1. No patients experienced immune effector cell–associated neurotoxicity syndrome (ICANS) or delayed neurotoxicity. Overall response rate (ORR) was 100%, with 42% complete response (CR), 25% very good partial response (VGPR), and 33% partial response (PR).
Four patients with high-risk FISH receiving teclistamab achieved a CR within 5 cycles. These data were superior to those of a control arm of lenalidomide and dexamethasone (n=3), in which the ORR was 66% with no CRs so far. In patients treated with teclistamab, the minimal residual disease (MRD) negative rate at 10-6 was 100% with no progression on treatment.
The final analysis of the phase 2 CENTAURUS study demonstrated long-term efficacy and safety for daratumumab monotherapy in patients with intermediate- or high-risk SMM. Conducted over a follow-up period extending to approximately 7 years, the study highlights the potential for daratumumab to delay the progression to MM in SMM patients who had been diagnosed for <5 years. Patients were randomized to receive daratumumab on one of three dosing schedules: intense (weekly in cycle 1, every 2 weeks in cycles 2 and 3, every 4 weeks in cycles 4–7, and every 8 weeks in cycles 8–20), intermediate (weekly in cycle 1 and every 8 weeks in cycles 2–20), and short (weekly 1 cycle only). A higher ORR and ≥CR rate was observed in the intense and intermediate arms, with a combined ≥CR rate of 8.5%. In addition, the 84-month overall survival (OS) rate was >80% across all dosing arms, with median OS not reached in any arm. Grade 3/4 treatment-emergent adverse events (TEAEs) were most frequent in the intense arm but were generally manageable across all groups. No new safety concerns arose from the extended follow-up.
A phase 2 study conducted by the National Institutes of Health highlights promising long-term results in patients with high-risk SMM (HR-SMM) treated with a combination of carfilzomib, lenalidomide, and dexamethasone followed by lenalidomide maintenance (KRd-R). The study aimed to investigate the durability of responses off therapy, following all patients completing lenalidomide maintenance. Patients with HR-SMM were enrolled based on specific risk criteria and underwent an induction phase with KRd-R followed by a 2-year lenalidomide maintenance phase.
At a median follow-up of >60 months:
The researchers concluded from these findings that “patients who achieve MRD-negative remissions after induction therapy have prolonged biochemical PFS,” although further follow-up is needed to fully understand the rates of PFS and OS.
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Jointly provided by the MMRF and RedMedEd.
This educational activity is supported by educational grants from AbbVie Inc., Bristol Myers Squibb, and GSK and sponsorship from Genzyme Corporation and Legend Biotech USA Inc.
