Triple Therapy Shows Promise for Elderly, Frail Patients With Previously Treated Multiple Myeloma

Xpovio (selinexor) with Velcade (bortezomib) and a low dose of dexamethasone demonstrates improved progression-free survival, overall response rate and safety in patients older and younger than 65 years of age with previously treated multiple myeloma regardless of frailty status, according to data published in the American Journal of Hematology.

Patients often receive a multiple myeloma diagnosis at a median age just under 70, and death occurs in patients at ages ranging from 65 years to 84 years. Although survival has increased for this population as a whole, older patients have not been able to benefit from newer therapies like younger patients.

“Elderly and frail patients with multiple myeloma are more vulnerable to the toxicity of the combination therapies, often resulting in treatment modifications and suboptimal outcomes,” the study authors wrote.

The researchers sought to compare efficacy and safety of Xpovio with Velcade and low-dose dexamethasone in 402 patients who were younger and older than 65 years of age, were either frail or not frail and had previously received between one and three lines of therapy. Patients were assigned one of two treatments:

• Triplet combination (195 patients) with 100 mg of oral Xpovio once per week, 1.3 mg/m2 of Velcade subcutaneously once per week and 40 mg of dexamethasone once per week
• Standard combination (207 patients) with 1.3 mg/m2 of Velcade subcutaneously twice per week with an 80-mg dose of dexamethasone until cycle 9, then Velcade was reduced to once per week with 40 mg of dexamethasone once per week.

Among the patients in this study, 60% (241 patients) were 65 years of age or older, with 109 patients receiving triplet combination therapy . In addition, 161 patients were younger than 65, of whom 86 patients were treated with the triplet combination regimen. There were 272 non-frail patients in the entire study, with 129 patients treated with triplet therapy and 143 patients who treated with combination therapy.

A prolonged progression-free survival (length of time after treatment the patients is still living with the disease without worsening) was seen in both age groups of patients treated with Xpovio. The same trend was also seen in both frail and non-frail patients. Non-frail patients specially had a significantly longer progression-free survival on Xpovio than without it (13.24 months versus 9.43 months). For frail patients, progression-free survival was 13.93 months with triplet therapy versus 9.46 months with standard combination therapy.

Patients who were at least 65 and were taking the treatment with Xpovio had a higher overall response rate (the percentage of people in the group who had a partial or complete response to treatment) than those not taking Xpovio, 76.1% versus 64.4%. This trend was also seen in those younger than 65 (76.7% versus 58.7%). Non-frail patients treated with standard combination therapy had a lower overall response rate compared with those treated with triplet therapy (62.9% versus 79.8%). This was not seen in frail patients (69.7% versus 60.9%, respectively).

All patient groups had higher rates of very good partial responses of better when treated with Xpovio compared to those treated without it.

Most patients had at least one treatment-related side effect. Compared with standard combination therapy, patients who received the triplet therapy had fewer moderate or worse peripheral neuropathy (numbness and weakness in the hands and feet from nerve damage) in those older than 65 years (22% versus 37%) and frail patients (15% versus 44%). Treatment-related side effects considered severe or worse did not occur more often in older patients compared with younger patients and in frail patients compared with non-frail patients.

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