Ninlaro Maintenance Therapy Prolongs and Boosts Treatment Benefits in Myeloma Patients, Study Says

Maintenance therapy with Ninlaro (ixazomib) can prolong and boost therapeutic responses from initial treatment in multiple myeloma patients who did not undergo an autologous stem cell transplant, a study says.

The study, “Ixazomib maintenance therapy in newly diagnosed multiple myeloma: An integrated analysis of four phase I/II studies,” was published in the European Journal of Haematology.

“There is increasing evidence for the clinical benefit of long-term, continuous therapy in patients with newly diagnosed multiple myeloma (NDMM), irrespective of whether they undergo autologous stem cell transplantation (ASCT),” the investigators said.

Long-term maintenance therapy with proteasome inhibitors (PI) such as Velcade (bortezomib) have recently become a cornerstone of multiple myeloma therapy. Proteasome inhibitors are substances that block the activity of a cellular complex that breaks down unnecessary or faulty proteins called proteasome. However, long-term maintenance therapy with Velcade may not be viable in most cases due to toxicity side effects.

Revlimid (lenalidomide) — an oral medication that promotes immune responses to help slow tumor growth — is the only treatment approved as a maintenance therapy for people with multiple myeloma in the U.S. and in Europe. However, it has only been approved for patients who had received ASCT.

Takeda‘s Ninlaro is another proteasome inhibitor, and the only one approved for use in combination with Revlimid and dexamethasone, which is a corticosteroid. With its established safety profile, the oral medication Ninlaro is a promising maintenance treatment for people with myeloma. It has shown positive results in newly diagnosed myeloma patients after a stem cell transplant.

To examine the safety and efficacy of long-term maintenance therapy with Ninlaro in patients who had not received ASCT, researchers performed an integrative analysis based on findings from four previous clinical trials.

Clinical data was pooled from three Phase 1/2 clinical trials — C16005 (NCT01217957), C16008 (NCT01383928), and C16006 (NCT01335685) — and one Phase 2 trial, C16020 (NCT02046070). All study participants received initial therapy once or twice per week, with one of the following three combinations:

• Ninlaro plus Revlimid and dexamethasone (IRd)
• Ninlaro plus melphalan and prednisone (IMP)
• Ninlaro plus cyclophosphamide and dexamethasone (ICd)

Melphalan and cyclophosphamide are cancer medications that interfere with the growth and spread of cancer cells in the body.

Initial treatment was followed by maintenance therapy with oral Ninlaro given at the last-tolerated dose used during induction therapy, until disease progression, death, or unacceptable toxicity.

A total of 215 patients across the four studies completed initial therapy, with 121 (56%) achieving disease stabilization. These 121 individuals were included in the integrative analysis.

Results showed that after a median maintenance therapy period of 10.6 months, 19 patients (16%) required dose reductions. At data cutoff, 94 patients (78%) stopped maintenance therapy completely, mostly due to disease progression (55%), followed by adverse events (7%), and patient’s withdrawal (5%).

The most common adverse events reported were diarrhea (27%), joint pain (17%), nausea (17%), pain at the extremities (17%), and upper respiratory infections (47%). Severe adverse events were reported in 24% of the patients.

Efficacy data showed the mean rates of complete response — no signs of cancer — increased from 22% at initial treatment to 35% following Ninlaro maintenance therapy. In addition, according to the integrative analysis, 28 patients (23%) saw their response to treatment increase during maintenance therapy.

“The observation that ixazomib maintenance can prolong and deepen responses achieved during ixazomib-based induction suggests that long-term ixazomib therapy may be associated with clinical benefit in patients with NDMM not undergoing ASCT,” the researchers said.

“The positive safety and efficacy profile of single-agent ixazomib maintenance reported here is in line with what has been recently reported for ixazomib maintenance in the post-ASCT setting. The Phase 3 TOURMALINE-MM4 study (NCT02312258) will report results of ixazomib maintenance vs. placebo in the post-induction NDMM patient population,” they added.