Sex Differences Play a Role in Molecular Risk Factors but do not Impact Efficacy in Multiple Myeloma

Contemporary Concepts | <b>Contemporary Concepts in Hematologic Oncology</b>

Despite women with multiple myeloma being more likely to have certain cytogenetic risk factors vs men, sex did not appear to impact efficacy.

Although women with multiple myeloma were more likely to fall into high-risk or ultra–high risk cytogenetic classifications vs men, sex was not associated with efficacy outcomes such as progression-free survival (PFS) or overall survival (OS), according to an article published in Clinical Lymphoma, Myeloma, and Leukemia.

Patients who were female were found to be more at risk for molecular risk lesions t(14; 16) at 4.2% vs 1.8% for male patients (P = .004) and del(17p) at 10.6% in female patients vs 7.4% for male patients (P = .023). Women were also more likely to have high-risk disease (35% vs 33%) and ultra-high-risk disease (13% vs 9.8%), and less likely to have standard-risk disease vs men (51% vs 57%; P = .026).

A total of 3894 patients enrolled on the study, of whom 2268 were male and 1626 were female. Patients had significant differences in characteristics, including hemoglobin, platelet count, and renal function. Moreover, women appeared to have a higher disease burden than men with investigators reporting a bone marrow plasma cell rate of 20% or higher at initial randomization in 45.2% of male patients and 47.3% of female patients.

Following induction chemotherapy, the overall response rate was 82.1% in male patients vs 80.3% in female patients. The percentage of patients who achieved a very good partial response was 54.4% vs 51.0% in both respective arms. Investigators did not find any differences between sexes in terms of PFS and OS from induction randomization. Median PFS in male patients was 25 months (95% CI, 24-26) vs 24 months (95% CI, 22-25) for female patients (HR, 1.01; 95% CI, 0.94-1.09; P = .699). Median OS was 67 months (95% CI, 62-70) for male patients and 70 months (95% CI, 64-73) for female patients (HR, 0.96; 95% CI, 0.87-1.05; P = .372). Of note, there were no differences in PFS and OS between the sexes for those who were randomized to receive different regimens, or randomized to maintenance lenalidomide (Revlimid) or observation.

For male patients with standard-risk disease, the median PFS was 29 months, 23 months for high-risk disease, and 16 months for ultra-high-risk disease (P <.001); the median OS was 77 months, 59 months, and 34 months in each respective subgroup (P <.001). For female patients with standard-risk disease, the median PFS was 27 months, 18 months for high-risk disease, and 17 months for ultra-high-risk disease (P <.001); the median OS was 82 months, 54 months, and 41 months in each respective subgroup (P <.001).

When male and female patients were compared in terms of risk categories, there was no significant difference in PFS. However, when OS was analyzed, there were similar outcomes for standard-risk and high-risk disease, but for ultra–high risk disease, the median OS was 34 months for male patients and 41 months for female patients (HR, 0.74; 95% CI, 0.52-1.04; P = .083).

For those with a del(17p) molecular risk lesions, the median PFS for male patients was 16 months vs 15 months for female patients (HR, 1.09; 95% CI, 0.76-1.56; P = .648) and the median OS was 28 months vs 32 months for each group, respectively (HR, 0.98; 95% CI, 0.66-1.45; P = .913). Those with t(4:14) molecular risk lesions the median PFS was 16 months for male patients and 18 months for female patients (HR, 0.89; 95% CI, 0.64-1.22; P = .456) and the median OS was 45 months vs 50 months in both respective groups (HR, 0.86; 95% CI, 0.58-1.26; P = .438). Additionally, those with t(4:16), the PFS was 16 months for males and 21 months for female patients (HR, 0.85; 95% CI, 0.44-1.63; P = .624) and the OS was 35 months for both sexes, with a later survival benefit in females (HR, 0.60; 95% CI, 0.29-1.23; P = .161).

Regarding adverse effects, female patients were more likely to have a lower neutrophil count during induction chemotherapy vs male patients, but this did not correlate with a higher risk of infection. Female patients were also likely to have diarrhea, nausea, and vomiting, and male patients were more likely to have myalgia.

Reference

Bird S, Cairns D, Menzies T, et al. Sex differences in multiple myeloma Biology but not clinical outcomes: results from 3894 patients in the myeloma XI trial. Clin Lymphoma Myeloma Leuk. 2021;21(10):667-675. doi:10.1016/j.clml.2021.04.013