Ninlaro Triple Combo Delays Progression of High-Risk Smoldering Multiple Myeloma, Trial Suggests

Early treatment with a triple combination therapy containing Ninlaro (ixazomib), Revlimid (lenalidomide), and dexamethasone in patients with high-risk smoldering multiple myeloma — a precursor of multiple myeloma — is safe and may halt the disease’s progression into the full-blown condition, a Phase 2 trial shows.

The results will be presented at the American Society of Hematology (ASH) 2019 Annual Meeting, Dec. 7–10 in Orlando, Florida, in a session titled “Phase II Trial of the Combination of Ixazomib, Lenalidomide, and Dexamethasone in High-Risk Smoldering Multiple Myeloma.”

Smoldering multiple myeloma is a preceding stage of multiple myeloma in which the patient does not have any symptoms but has a significantly higher risk of developing the full-blown condition than the general population.

Usually, patients with precursor conditions only receive treatment once symptomatic multiple myeloma develops, but studies have suggested that early treatment, particularly in smoldering multiple myeloma patients at high risk of progressing, may delay or even halt myeloma progression.

Researchers at the Dana-Farber Cancer Institute had already shown in a Phase 2 trial (NCT02279394) that a combination of Empliciti (elotuzumab), Revlimid, and dexamethasone reduces tumor burden in most patients (84%) with high-risk smoldering multiple myeloma, completely eliminating traces of precursor tumor cells in 6% of patients.

The combination also kept all patients from progressing into full-blown multiple myeloma after nearly two years of follow-up.

Now, the same team of researchers teamed up with Celgene and Takeda to investigate another triple combination — Ninlaro, Revlimid, and dexamethasone — in the same group of patients.

To date, the Phase 2 trial (NCT02916771) has included 53 patients with high-risk smoldering multiple myeloma — 22 men and 32 women, median age of 61 years — 45 of whom have received at least one treatment cycle.

The triple combination will be administered in nine four-week cycles, after which patients will be given maintenance therapy with Ninlaro and Revlimid for an additional 15 cycles.

The study’s primary goal is to determine whether the proportion of patients who did not progress two years after starting treatment is higher than 75%. Secondary endpoints include progression-free survival (time the patient lives with the disease without it getting worse), response rate, time to progression, overall survival, and safety of the combination therapy.

Among the 45 patients who completed at least one cycle of therapy, 91.1% experienced a reduction in disease burden after treatment. This included 31.1% complete responses (or the total absence of precursor myeloma cells), 20% very good partial responses, and 40% partial responses, and 10% minimal responses.

Responses were particularly promising in patients who completed the full nine cycles of induction therapy (97%), which included 42.4% complete responses and 27.2% very good partial responses.

To date, six patients have completed the treatment and are being followed. No patient has progressed to full multiple myeloma.

The treatment was well-tolerated with the most frequent severe (grade 3) adverse events being high blood pressure, low phosphate levels, and rash. Life-threatening (grade 4) adverse events included low levels of platelets and neutrophils, as well as high blood sugar.

Results from minimal residual disease testing, which refers to small numbers of cancer cells that remain in the person during or after treatment, is ongoing for patients who achieved complete or very good partial responses and will be presented at the meeting.

“The combination of ixazomib, lenalidomide, and dexamethasone is an effective and well-tolerated intervention in high-risk smoldering myeloma” with 91% overall response rate and 54.7% complete responses and very good partial responses to date, the researchers wrote.

“The high response rate, convenient schedule and manageable toxicity build on prior studies which have shown efficacy of lenalidomide and dexamethasone in high risk smoldering myeloma. Longer follow-up for disease outcome is ongoing,” they said.

In addition to this study, Dana-Farber researchers will present more than 40 studies relating to multiple myeloma, leukemia, and stem cell transplant at the ASH annual meeting, according to a press release.