Maintenance therapy with Ninlaro and Revlimid in patients with recently diagnosed multiple myeloma who underwent a stem cell transplant may safely improve survival, although more research is needed especially in high-risk patients.
Maintenance therapy with Ninlaro (ixazomib) and Revlimid (lenalidomide) may improve progression-free survival compared with Revlimid alone in patients with myeloma who recently underwent a stem cell transplant, according to recent study results.
In addition, this combination maintenance therapy was safe and tolerable in patients, according to the study published in Clinical Cancer Research.
This phase 2 study started in 2012, when Revlimid maintenance was recently approved by the Food and Drug Administration for patients with myeloma. This approval was based on studies published a year or two before, which demonstrated that Revlimid maintenance after stem cell transplant improved progression-free survival (the length of time after stem cell transplant that a patient lives with cancer without disease progression) by at least a year and a half. Other studies showed that patients also had improvements in overall survival (the time a patient with cancer is still alive) with Revlimid maintenance compared with placebo.
“Our goal was how can we make that even better, so combination maintenance,” said Dr. Krina K. Patel, an associate professor and center medical director for the Department of Lymphoma-Myeloma at The University of Texas MD Anderson Cancer Center in Houston, in an interview with CURE®. “This is one of the first studies that looked at that combination.”
Maintenance Therapy After Stem Cell Transplant
In this study, researchers assessed the effects of maintenance therapy with Ninlaro and Revlimid in 64 patients (65.6% men; 64.1% aged 60 years and older) with newly diagnosed multiple myeloma who underwent autologous stem cell transplant. Of note, maintenance therapy was initiated within 60 to 180 days after stem cell infusion.
“(Ninlaro) is (an) oral (drug), which is really important when we’re doing maintenance because these patients have just gone through a stem cell transplant, they just had chemo right before that,” Patel said. “Their myeloma’s usually under control, and now we’re just trying to keep it controlled for longer before we have to treat it again. (An) oral (drug) makes a huge difference.”
Researchers monitored several factors throughout the study including progression-free survival, overall survival and duration of response (the time the disease responds to a treatment without growth or spread).
“We wanted to see if adding a (proteasome inhibitor) that’s easier to take, which is a once-a-week pill, or (else) patients will have to come into the hospital, etc., will be safe, No. 1, and it won’t cause more toxicity, but No. 2, is there a signal that this could actually be better than (Revlimid) maintenance,” Patel said.
In 39 patients, rates of response to maintenance therapy deepened over time. In particular, 43% of patients achieved a complete response (disappearance of all signs of cancer from treatment, although it does not denote a cure to the disease), and a median overall survival was not reached during a median follow-up of 62 months. Of note, when median overall survival is not reached, this means that at least half of patients in the study were alive at the time researchers assessed this factor.
Median progression-free survival in all patients in the study was 73 months and had not been reached in patients with stage 1 disease. The nine patients with stage 3 disease had a median progression-free survival of 34 months, and the 14 patients with high-risk disease had a median progression-free survival of 25 months.
“The high-risk patients, which is where we were hoping it would have the most benefit — unfortunately, we didn't have very many high-risk patients on the study,” Patel said. “High-risk patients still need better options (for maintenance therapy) out there.”
Progressive disease was observed in 22 patients, and 19 patients continued to receive maintenance therapy with this two-medication approach.
The most common severe or life-threatening side effects that occurred throughout the study included leukopenia (low white blood cell count), neutropenia (low counts of neutrophils, a type of white blood cell), lung infections, thrombocytopenia (low blood platelet count), maculopapular rash (a rash with flat and raised areas) and diarrhea. Nine patients developed second primary malignancy.
Toxicity led to a Ninlaro dose reduction in 20 patients and a Revlimid dose reduction in 31 patients. Four patients discontinued Ninlaro because of toxicity.
Mild or moderate neuropathy (weakness, pain and numbness from nerve damage in the hands and feet) was observed in 22 patients and led to a dose reduction or discontinuation of Ninlaro in two patients.
‘Phenomenal’ Safety and Ease With Combination Maintenance
“Most of these patients actually did well with both drugs,” Patel said. “The toxicities, we actually saw less neuropathy than you would with bortezomib (Velcade), for instance, which a lot of people do use in combination with (Revlimid) for maintenance, especially high-risk patients. … The safety and the ease were pretty phenomenal for most of these patients.”
There are several limitations to this study including the fact that it had 64 patients, making it a smaller study, and that most patients had standard risk compared with a higher risk.
“To be tolerated well and to be able to get this great (progression-free survival), of course, we need randomized trials to really prove that (progression-free survival) is significantly better than (Revlimid) maintenance alone,” Patel said. “I do think that there are patients that really would benefit (from this maintenance approach).”
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