The lymphocyte/monocyte ratio predicts the efficacy of isatuximab plus pomalidomide in multiple myeloma patients

Abstract

Background: Isatuximab, an anti-CD38 antibody, has been widely used in treatments for patients with relapsed/refractory multiple myeloma (MM). Despite its high efficacy, not all patients achieve a lasting therapeutic response with isatuximab.

Objective: We tried to identify biomarkers to predict the effectiveness of isatuximab by focusing on the host's immune status before treatment.

Methods: We retrospectively analyzed the cases of 134 relapsed/refractory MM patients in the Kansai Myeloma Forum database who had received only a first isatuximab treatment.

Results: Among the 134 patients, an isatuximab, pomalidomide and dexamethasone (Isa-PD) regimen, isatuximab, carfilzomib and dexamethasone (Isa-KD) regimen and isatuximab and/or dexamethasone (Isa-D) regimen were used in 112, 15 and 7 patients, respectively. The median age at treatment, number of prior treatment regimens, and progression-free survival (PFS) were 71, 6, and 6.54 months, respectively. Multivariate analysis showed that the PFS under the Isa-PD regimen was longer in patients with higher lymphocyte/monocyte ratio (LMR ≥ 4), fewer prior treatment regimens (< 6), and no use of prior daratumumab treatment. The OS under the Isa-PD regimen was longer in patients with higher white blood cell counts (WBC counts ≥ 3000/μL) and higher LMR. The PFS under the Isa-D regimen was longer in patients with fewer prior treatment regimens in univariate analysis, but no parameters were correlated with PFS/OS under the Isa-KD regimen.

Conclusion: We found that the patients with higher LMR (≥ 4) could obtain longer PFS and OS under the Isa-PD regimen. Other cohort studies of isatuximab treatment might be necessary to substantiate our results.

Keywords: Isatuximab; Lymphocyte/monocyte ratio; Multiple myeloma; Predictive markers.

Fig. 1

A The progression-free survival (PFS) of the multiple myeloma (MM) patients treated with isatuximab. The entire cohort was used to calculate PFS. Median PFS (months) values with the 95% CI (confidence interval) are shown. B The PFS of the MM patients under the following regimens: isatuximab, pomalidomide and dexamethasone (Isa-PD, black); isatuximab, carfilzomib and dexamethasone (Isa-KD, red); and isatuximab and dexamethasone (Isa-D, blue). One-year PFS values (%) with the 95% CI are shown. C The PFS of the MM patients under the Isa-PD regimen according to the lymphocyte/monocyte ratio (LMR): 4 or more (black) or less than 4 (red). The hazard ratio (HR) with the 95% CI is shown. The survival curves were adjusted by the significant factors in the multivariate analysis. D The PFS of the MM patients under the Isa-PD regimen according to the number of previous regimens: 6 or more (black) or less than 6 (red). The hazard ratio (HR) with the 95% CI is shown. The survival curves were adjusted by the significant factors in the multivariate analysis. E The PFS of the MM patients under the Isa-PD regimen according to the prior use of daratumumab (DARA): No (black) or Yes (red). The hazard ratio (HR) with the 95% CI is shown. The survival curves were adjusted by the significant factors in the multivariate analysis. F The PFS of the MM patients under the Isa-PD regimen according to the high risk cytogenic abnormalities: none (black) or at least one (red). The hazard ratio (HR) with the 95% CI is shown. The survival curves were adjusted by the significant factors in the multivariate analysis. The number of patients at risk in each group is shown in the lower panel of each figure

Fig. 2

A The overall survival (OS) of the MM patients for the entire cohort. Median OS (months) with the 95% CI is shown. B The overall survival (OS) of the MM patients under the Isa-PD regimen according to the white blood cell (WBC) counts: 3000/μl or more (black) or less than 3000/μl (red). The hazard ratio (HR) with the 95% CI is shown. The survival curves were adjusted by the significant factors in the multivariate analysis. C The OS of the MM patients under the Isa-PD regimen according to the lymphocyte/monocyte ratio (LMR): 4 or more (black) or less than 4 (red). The hazard ratio (HR) with the 95% CI is shown. The survival curves were adjusted by the significant factors in the multivariate analysis. The number of patients at risk in each group is shown in the lower panel of each figure

Fig. 3

A The PFS of the MM patients under the Isa-PD regimen according to prior use of DARA: No (black); Yes but treated with isatuximab less than 6 months after the last DARA treatment (red); and Yes but treated with isatuximab 6 months or later after the last DARA treatment (blue). One-year PFS (%) with the 95% CI, the HR with 95% CI, and the p-value are shown. B The OS of the MM patients under the Isa-PD regimen according to prior use of DARA: No (black); Yes but treated with isatuximab less than 6 months after the last DARA treatment (red); and Yes but treated with isatuximab 6 months or later after the last DARA treatment (blue). One-year PFS (%) with the 95% CI, the HR with 95% CI, and the p-value are shown. The number of patients at risk in each group is shown in the lower panel of each figure