Ninlaro Could Replace First-line Velcade in Older Myeloma Patients, Study Suggests

Older multiple myeloma patients who are unable to receive a stem cell transplant could receive Ninlaro (ixazomib) as part of their first line-therapy instead of standard Velcade (bortezomib), according to the results of a clinical trial.

While Ninlaro- and Velcade-based therapies showed similar response rates, oral dosing and a better safety profile make Ninlaro a more suitable approach for such patients.

The study, “A Phase I/II Dose-Escalation Study Investigating All-Oral Ixazomib-Melphalan-Prednisone Induction Followed By Single-Agent Ixazomib Maintenance In Transplant-Ineligible Newly Diagnosed Multiple Myeloma,” was published in the journal Haematologica.

Recent advances in the treatment of multiple myeloma are associated with significant improvements in both progression-free survival (PFS) — the time a patient lives without signs of disease progression — and overall survival (OS).

However, older patients who are unable to tolerate high-dose therapy followed by an autologous stem cell transplant (when the patient’s own blood-forming stem cells are collected) tend to experience significantly worse outcomes.

The current standard of care for elderly patients with newly diagnosed myeloma who are not eligible for stem cell transplants is the VMP regimen — a combination of Velcade, a proteasome inhibitor; melphalan, a chemotherapeutic agent; and prednisone, an immunosuppressant.

However, Velcade is administered parenterally, which refers to an injection or infusion. This can be difficult to tolerate for elderly patients, limiting its feasibility as a long-term treatment.

Therefore, there is a current unmet need for a tolerable, effective, and convenient proteasome inhibitor (PI) option for elderly patients with untreated, transplant-ineligible myeloma.

Ninlaro is a PI that is taken orally and has a safety profile that can allow for long-term dosing. It is approved in 50 countries for use in combination with Revlimid (lenalidomide) and dexamethasone for the treatment of myeloma patients who have received at least one prior form of therapy.

Researchers conducted this Phase 1/2 trial (NCT01335685) to investigate the effectiveness and safety of oral Ninlaro in combination with melphalan and prednisone (IMP) as an induction regimen, followed by long-term maintenance with single-agent Ninlaro in elderly, transplant-ineligible patients.

The goal of induction therapy — the first phase of multiple myeloma treatment — is to reduce the number of myeloma cells in the bone marrow. Maintenance therapy usually involves giving a drug at a low dose over a long period of time, which helps keep the person in remission and prevents relapse.

The objective of the Phase 1 part was to determine the safety and recommended Phase 2 dose of IMP.

Among the 38 patients evaluated for safety, 10 experienced severe adverse events, including low neutrophil and platelet levels.

The objective of the Phase 2 part was to determine the complete and very good partial response rates. Patients received the recommended Phase 2 dose, which was determined in the Phase 1 study.

Results showed that 48% of patients experienced either a complete or a very good partial response rate, including 28% (22% at the recommended dose) with a complete response or better.

The regimen also showed significant tolerability over a long treatment period, as more than half of patients proceeded to maintenance therapy. The duration of therapy lasted up to 4.8 years in some patients.

Patients were followed up for a median of 43.6 months, and showed a median PFS of 22.1 months and an overall survival of 54.4 months,  suggesting that this regimen can lead to good long-term outcomes.

The adverse events reported included hematologic and gastrointestinal events, and well as  peripheral neuropathy (damage to nerves). The majority occurred during the induction period.

Only 6% of patients discontinued Ninlaro maintenance therapy due to adverse events, and no on-study deaths occurred during the maintenance period.

“The data from this study suggests that all-oral IMP induction followed by single-agent ixazomib maintenance is an active and well-tolerated front-line regimen in transplant-ineligible patients with [newly-diagnosed multiple myeloma],” researchers wrote.