Before I pass along important information about Takeda’s new oral proteasome inhibitor, Ninlaro (ixazomib), I wanted to share an update about how I’m doing.
Much better, thank you very much! Squirting a shot of vancomycin liquid into the back of my mouth (yuck) every six hours seems to be doing the trick. Another antibiotic, Flagyl, is usually tried first in C. diff patients. But my doctors didn’t want to mess around and used the heavy artillery right away.
My fever is gone. I feel like myself again. Still need to hit the porcelain God every hour or two.
I’m scheduled to be discharged tomorrow around noon. A PET scan in the afternoon and I’ll hold up at one of the local hotels until I see Dr. Tricot on Thursday.
Now I remember why I’m here: Did the second transplant squash my myeloma–at least for a while? What maintenance therapy does Dr. Tricot have in mind?
Funny. We get caught up in the testing schedules, complications and side effects and lose sight of the big picture. Thursday is a reality check for me. Hopefully I’ll be back to normal by then; my bottom is getting pretty sore.
So what’s Ninlaro’s story. Another proteasome inhibitor? Ho hum. It may not be as “sexy.” as one of the new immunotherapies. Guess I’m as guilty as anyone in neglecting news about Ninlaro here at MMB. But that doesn’t mean I don’t think Ninlaro is going to be a great drug.
Preliminary data shows Ninlaro to be effective as a single agent; even better when combined with Revlimid. Although the numbers are in the same neighborhood as the current medical standard of care–Revlimid, Velcade and dexamethasone (RVD)–the prospect of an all oral therapy regimen does excite a lot of patients.
No more weekly trips to the infusion center. Instead, a patient can take one Ninlaro capsule, once a week, for three weeks on/one week off, along with their daily Revlimid or Thalomid for the same three weeks on/one week off.
Combining Ninlaro with Thalomid? My guess is docs won’t be shy trying the combination. Bet there are (or will be) a number of studies teaming the two drugs; thalidomide is still a standard of care for use against multiple myeloma in a number of budget conscious countries.
Even better? How about teaming Ninlaro up with Pomalyst (pomalidomide)? Turns out there is some early data about this. And it looks very promising for use in “experienced” or late stage patients that are refractory to Revlimid and/or Velcade.
Now that’s exciting!
Check out this article in Medpage Today yesterday:
Pomalidomide and Ixazomib Pair Up in Refractory Myeloma
December 13, 2015 – MEDPAGE TODAY
ORLANDO — Researchers are already using the new oral proteasome inhibitor ixazomib (Ninlaro), approved just prior to the American Society of Hematology meeting here, in combination with standard treatment backbones for people diagnosed with refractory and/or relapsed multiple myeloma.
Although the Phase 1 study’s goal was to find a tolerated treatment dose, Peter Voorhees, MD, associate professor of medicine at the University of North Carolina School of Medicine, Chapel Hill, said that of 20 evaluable patients, one patient achieved a very good partial response and 10 other patients achieved an objective partial response and another three patients achieved disease stabilization. Six of the patients progressed.
All five patients with standard risk characteristics achieved a partial response, and six of 13 patients with high-risk prognostic factors achieved partial responses, he reported at the annual meeting of the American Society of Hematology.
“Three of the 6 the patients who were refractory to lenalidomide (Revlimid) and dexamethasone achieved partial responses with ixazomib and pomalidomide (Pomalyst) with dexamethasone,” Voorhees said. “The preliminary efficacy is promising.”
The combination also appeared to allow eight partial responses among the 14 patients who were found to be refractory to sequential lenalidomide and proteasome inhibitor therapy.
“Pomalidomide, ixazomib and dexamethasone can be combined safely,” Voorhees said, “But moderate to severe hematologic toxicity is common and requires close monitoring and supportive care.”
He illustrated that some of the patients have remained on treatment after 22 cycles. “Many of these responses have proven durable, even at the lower dose cohorts,” he said. In the standard three plus three dose escalation design, patients tested three different doses of pomalidomide — 2 mg, 3 mg and 4 mg; and three different doses of ixazomib — 2.3 mg, 3 mg and 4 mg; dexamethasone was provided at a dose of 40 mg for patients less than 75 years of age; the dose was reduced to 20 mg for patients 75 years of age or older. Dose limiting toxicities — febrile neutropenia — emerged at dose level 3 and dose level 4, Voorhees said.
“Dose level 3 – 4 mg of pomalidomide and 3 mg of ixazomib was well tolerated,” he said.
The patients were about 65 years of age. They had been diagnosed with multiple myeloma for a median of 5.18 years; about 2/3 of the cohort were men, and 77% were Caucasian. All the patients were in ECOG Performance Status of 0-1. About 59% of the 22 patients studied at baseline were identified as having high-risk cytogenetics.
Voorhees said that the median number of prior therapies was three. He said 100% of the 22 patients had been exposed to bortezomib (Velcade), lenalidomide, and corticosteroids. Of the 22 patients evaluable for safety, 14 have come off study — 11 due to disease progression; two due to an adverse event (a grade 2 motor neuropathy and febrile neutropenia), and one patient just preferred to leave the study.
Ken Shain, MD, PhD, assistant member at the Moffitt Cancer Center and professor of oncologic sciences at the University of South Florida, Tampa, told MedPage Today, “Ixazomib has been approved about a week and it is already being combined with other drugs, as always happens, in treating relapsed or refractory multiple myeloma.
“Ixazomib as an oral drug is an exciting agent by itself and provides a novel way that we can dose our patients in a more convenient fashion while maintaining efficacy,” he said. “I think this is a great way to go. We know that proteasome and IMID (immunomodulatory drugs) are highly effective without significant toxicities. So to be able to provide an all-oral regimen is really a breakthrough.”
He said that researchers will have to “feel out” whether there is a difference in using ixazomib with pomalidomide or other agents such as lenalidomide. “There have been no studies comparing the 2 immunomodulatory agents. I would suggest they will serve 2 different patient populations — early treatment and relapses with lenalidomide combination; and later relapses with pomalidomide combination.”
Shain disclosed relevant relationships with Celgene, Amgen, and Takeda.
Vorhees disclosed relevant relationships with Millennium, Takeda, and Celgene.
A couple of things to think about. First, I’ll admit the numbers don’t knock you over. But remember that the primary purpose of a Stage 1 trial is to identify the maximum safe dose for patients. Since some of the patients were on lower doses than common sense tells us they should use, chances are they won’t respond as well. So the fact nearly every patient showed some improvement is encouraging.
Second, note that 8 out of 14 patients responded that were already refractory (resistant) to an IMiD (Thalomid, Revlimid) and a proteasome inhibitor (Velcade or Kyprolis).
That’s me! Something tells me I may be using Ninlaro soon.
My understanding is Takeda is doing ongoing maintenance studies featuring Ninlaro, too. That would be very helpful.
Feel good and keep smiling! Pat