LocoMMotion: a prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed and/or refractory multiple myeloma

Abstract

Despite treatment advances, patients with multiple myeloma (MM) often progress through standard drug classes including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies (mAbs). LocoMMotion (ClinicalTrials.gov identifier: NCT04035226) is the first prospective study of real-life standard of care (SOC) in triple-class exposed (received at least a PI, IMiD, and anti-CD38 mAb) patients with relapsed/refractory MM (RRMM). Patients (N = 248; ECOG performance status of 0–1, ≥3 prior lines of therapy or double refractory to a PI and IMiD) were treated with median 4.0 (range, 1–20) cycles of SOC therapy. Overall response rate was 29.8% (95% CI: 24.2–36.0). Median progression-free survival (PFS) and median overall survival (OS) were 4.6 (95% CI: 3.9–5.6) and 12.4 months (95% CI: 10.3–NE). Treatment-emergent adverse events (TEAEs) were reported in 83.5% of patients (52.8% grade 3/4). Altogether, 107 deaths occurred, due to progressive disease (n = 74), TEAEs (n = 19), and other reasons (n = 14). The 92 varied regimens utilized demonstrate a lack of clear SOC for heavily pretreated, triple-class exposed patients with RRMM in real-world practice and result in poor outcomes. This supports a need for new treatments with novel mechanisms of action.

Ciltacabtagene Autoleucel, an Anti–B-cell Maturation Antigen Chimeric Antigen Receptor T-Cell Therapy, for Relapsed/Refractory Multiple Myeloma: CARTITUDE-1 2-Year Follow-Up

“…Indirect treatment comparisons between the CARTITUDE-1 results and real-world SOC, in data sets comprising European and/or US patients (MAMMOTH study and the prospective LocoMMotion study), found that cilta-cel significantly improved outcomes versus real-world therapies in triple-class exposed patients with RRMM. 3,25 In a matching-adjusted indirect treatment comparison using data from the similarly designed CARTITUDE-1 14 and KarMMa 13 trials, cilta-cel appeared to have higher response rates and longer DOR and PFS than ide-cel. 26 After a MFU of 13.3 months, the ORR in the KarMMa trial was 73% across all dose cohorts (33% CR or better) and 81% with the highest dose evaluated (450 × 10 6 cells; 39% CR or better).…”

“…1 However, patients may eventually become resistant to these treatments. 2,3 Lower depth and durability of response have been reported with each successive line of therapy (LOT), 4 and patients who are refractory to multiple drug classes have suboptimal outcomes. The median overall survival (OS) with SOC is 11.2 months for patients who are refractory to < 3 prior LOT and 5.6 months for penta-refractory patients (refractory to anti-CD38 antibody, two PIs, and two IMiDs).…”

Real-World Outcomes of Belantamab Mafodotin for Relapsed/Refractory Multiple Myeloma (RRMM): Preliminary Results of a Spanish Expanded Access Program (EAP)

“…Patients who are refractory to the standard drug classes (PIs, IMiDs, and anti-CD38 mAbs), otherwise known as triple-class refractory MM, have a poor prognosis (limited overall survival [OS] and progression-free survival [PFS] outcomes), with an estimated OS of less than 1 year [ 3 , 5 ]. Therapeutic options for both triple-class refractory [ 5 ] and refractory MM patients who were triple-class exposed [ 11 ] are limited, representing a population with a fairly clear unmet medical need [ 3 ].…”

Adjusted comparison of outcomes between patients from CARTITUDE-1 <i>versus</i> multiple myeloma patients with prior exposure to proteasome inhibitors, immunomodulatory drugs and anti-CD38 antibody from the prospective, multinational LocoMMotion study of real-world clinical practice

“…Detailed safety findings for CARTITUDE-1 18 and LocoMMotion 20,21 have been previously reported elsewhere. Unadjusted comparison of all AEs shows higher rates of AEs for cilta-cel vs.…”

“…This was also the case for grade 3/4 events (93.8% vs. 49.2%, Table 4). Mateos et al 21 reported AEs as being underreported for RWCP in LocoMMotion due to its observational nature. Six (6.2%) patients treated with cilta-cel and nineteen (7.7%) patients with RWCP experienced an adverse event with an outcome of death.…”