From March 24, 2022, to October 6, 2023, we examined 171 samples from 57 patients: 23 newly diagnosed and 34 who had at least one relapse. Patient demographics are summarized in Table 1. No outliers were observed for renal impairment (i.e. eGFR < 40 mL/min per 1·73 m2 or creatinine > 2 mg/dL). sBCMA was measurable in all patients, including those with solitary plasmacytoma and non-secretory disease (2 patients) and those receiving anti-BCMA-targeted therapies (5 patients, treated with belantamab mafodotin and teclistamab); further details on the treatments received are provided in Table 2.
Table 1
Patients’ baseline characteristics.
| Age—yr (range) | 68 (53–87) |
| Gender female/male no. (%) | 21 (36.8) / 36 (63.2) |
| ECOG | |
| 0 | 8 (14.1) |
| 1 | 28 (49.1) |
| 2 | 15 (26.3) |
| 3 | 6 (10.5) |
| M Protein | |
| IgG κ | 26 (45.6) |
| IgG λ | 5 (8.7) |
| IgA κ | 7 (12.3) |
| IgA λ | 5 (8.7) |
| Light chain κ or λ | 5 (8.7) / 4 (7.1) |
| IgD λ or IgM κ | 1 (1.8) / 1 (1.8) |
| IgG κ + IgM κ | 1 (1.8) |
| NS/SP | 2 (3.5) |
| Newly diagnosed pts. | 23 (40.4) |
| ASCT eligible | 10 (17.5) |
| Relapsed or refractory pts. | 34 (59.6) |
| 1st relapse | 18 (31.5) |
| 2nd relapse | 9 (15.8) |
| 3rd or higher relapse | 7 (12.3) |
| Renal impairment at T0 | 7 (12.3) |
Table 2
Summary of the different treatments received by patients during data analysis.
| Regimens | Patients no. | NDMM/RRMM |
| Belantamab | 3 | 0/3 |
| DaraRD | 22 | 8/14 |
| Daratumumab | 1 | 0/1 |
| DaraVD | 2 | 0/2 |
| DaraVTD | 11 | 10/1 |
| EloPD | 2 | 0/2 |
| IsaKD | 1 | 0/1 |
| IsaPD | 1 | 0/1 |
| IxaRD | 1 | 0/1 |
| KD56 | 2 | 0/2 |
| KRD | 1 | 0/1 |
| MP | 1 | 1/0 |
| PACE | 1 | 0/1 |
| PVD | 1 | 0/1 |
| RD | 3 | 2/1 |
| Teclistamab | 2 | 0/2 |
| VMP | 2 | 2/0 |
| DaraRD, daratumumab plus lenalidomide-dexamethasone. DaraVD, daratumumab plus bortezomib-dexamethasone. DaraVTD, daratumumab plus bortezomib, thalidomide-dexamethasone. EloPD, elotuzumab pomalidomide-dexamethasone. IsaKD, isatuximab plus carfilzomib-dexamethasone. IsaPD, isatuximab plus pomalidomide-dexamethasone. IxaRD, ixazomib plus lenalidomide-dexamethasone. KD56, carfilzomib plus dexamethasone. KRD carfilzomib plus lenalidomide-dexamethasone. MP, melphalan plus prednisone; NDMM, Newly Diagnosed Multiple Myeloma; PACE, cisplatin plus doxorubicin-cyclophosphamide-etoposide; PVD, pomalidomide plus bortezomib-dexamethasone; RD, lenalidomide plus dexamethasone; RRMM, Relapsed/Refractory Multiple Myeloma; VMP, bortezomib plus melphalan-prednisone. |
The sBCMA levels showed extensive diversity at T0: median sBCMA values at T0 were higher in newly diagnosed patients than in relapsed patients. Value distribution was normalized by log transformation and statistical analysis revealed a significant difference in sBCMA log at T0 both across 5 subgroups (OneWay ANOVA p = 0.0009) and on patients grouped in two categories at diagnosis (TE or nonTE) and at relapse (patients at first, second, third or more relapse: R1, R2 or R3 respectively) (t test p = 0.0335). Detailed analysis is reported in Supplementary Information 1 (SI 1A-1F).
The percentage decrease in sBCMA after the first month of theraphy (T1-T0) was analyzed both in 5 subgroups and in patients grouped as newly diagnosed or relapsed (data detailed in Supplementary Information 2; SI 2A-D). The analysis showed moderate differences within the 5 groups (p = 0.0117) confirmed by the difference between the low median of the R3 patients and nonTE and TE (Fig. 1A). When patients were grouped (newly diagnosed vs relapsed) the median reduction was higher for the former and the statistically significant difference was confirmed with a p = 0.0027 (Fig. 1B).
A similar analysis was performed on the percentage of sBCMA decrease after 6 month of theraphy (T2-T0). The percentage decrease in sBCMA from T0 to T2 was analyzed again both in 5 subgroups (Fig. 1C) and in patients grouped as newly diagnosed or relapsed (Fig. 1D), without showing a statistically significant difference between the groups, even if in the first-line therapy the median decrease was higher (90%) than in the salvage therapy (74.5%) and a moderate trend was observed. It is worthnote that the lack of significance at 6 months is mainly due to the only two negative sBCMA decrease occurred in the two newly diagnosed patients that experienced PD (data not shown). Quality of clinical response (QoR) was assessed after 1 month and after 6 months. After 6 months of therapy, 21 of the 57 patients had a complete or very good partial response (CR/VGPR), 27 had a partial response (PR); 9 experienced progressive disease (PD).
A possible relationship between the absolute levels of sBCMA (or their log) at T0 and QoR was sought but no correlation was found, demonstrating that the therapeutic response does not depend on the sBCMA level at the start of therapy
The QoR weakly correlated with the percentage of decrease of sBCMA after one month (Spearman's r=-0.2648; p = 0.0465). The median decreases were 78.1%, 78.5% and 43.5% in patients with CR/VGPR, PR and PD, respectively, and the only faint significant difference (p = 0.0315) appeared between patients with CR/VGPR and those with PD when analyzed separately (Fig. 2A).
When the percentage decrease in sBCMA after 6 months was evaluated in relation to response, a higher statistically significant correlation was found (Spearman's r=-0.5236; p < 0.0001). In CR/VGPR patients the median T2-T0 was 91.8%, while in PR and PD it was 80.9% and − 2.5%, respectively.
The further analysis of the data by Kruskal-Wallis showed a highly significant differences (p value = 0.0001). Subsequent multiple comparison analysis followed by Mann-Whitney did not show significant differences between the decrease in the CR/VGPR and PR groups (although a trend seemed to appear with a p = 0.0737) while demonstrated a high statistically significant differences between PD patients and the other two groups (CR/VGPR and PR), showing p < 0.0001 and p = 0.0005 respectively (Fig. 2B).