MedPage Today reported on a new, retrospective study involving Kyprolis over the weekend. It makes my myeloma specialist, Dr. Tricot, look pretty smart for using Kyprolis as part of my three drug post transplant consolidation therapy.
According to the study, close to 50% of patients who have previously used Velcade and/or Revlimid responded to Kyprolis as a salvage therapy. However, the study isn’t without controversy. Here’s the first part of the article:
Adding Carfilzomib to Myeloma Salvage Boosts Response Rate
Patients fare better with combo regimen than dose increase
The use of regimens containing carfilzomib (Kyprolis) for the treatment of relapsed and/or refractory multiple myeloma (RR-MM) in patients previously exposed to bortezomib (Velcade) and lenalidomide (Revlimid) yielded an overall response rate (ORR) of 47.2% with manageable toxicity, a retrospective multicenter study has shown.
Predictors of response included refractoriness to bortezomib (ORR 68% for bortezomib-sensitive patients versus 42.2% for bortezomib-resistant patients, P=0.02), and to lenalidomide (ORR 75% for lenalidomide-sensitive patients versus 40.8% for lenalidomide-resistant patients, P=0.003), said researchers. The number of prior lines of therapy also had an impact on response rate, as did albumin <35 g/L, according to Eli Muchtar, MD, of the Rabin Medical Centre in Petah Tikva, Israel, and colleagues.
This study provides important data on predictors of response to carfilzomib and supports combination treatment to improve response, although the optimal combination has yet to be determined,” the investigators reported online in the British Journal of Haematology. “As drug resistance is an important factor in determining response quality to carfilzomib in this study, a better understanding of the resistance mechanism(s) can help in both treatment selection as well as in creating ways to overcome it.”
This paper adds nothing to the literature, commented Ravi Vij, MD, of Washington University School of Medicine in St. Louis. As far as predictors of response are concerned, “they are already known and self-evident,” he told MedPage Today. “You need randomized controlled prospective studies with an independent response assessment committee. Why publish this rubbish?”
Dr. Noopur Raje, director of the Center for Multiple Myeloma at Massachusetts General Cancer Center in Boston, agreed. “I don’t think this paper adds a whole lot and I don’t think refractoriness to these two (bortezomib and lenalidomide) reflects response rate either,” she said. “This is not a practice-changing paper,” she told MedPage Today.
Raje pointed to the ENDEAVOUR trials and noted that carfilzomib is already proving efficacious in the relapsed setting, even in patients who are refractory to bortezomib and/or lenalidomide.
“We certainly have had a lot of new treatment options in the past year with four new drugs approved so we’re making improvements,” noted Vij. In addition, there are new trials in the works, including licensing trials, he said.
Use of a higher dose of carfilzomib has resulted in the emergence of a slightly different toxicity profile that includes renal insufficiency and cardiac toxicity, pointed out Vij. “We do see treatment related complications that need to be appropriately managed,” said Raje.
Dr. Raje spoke to our group at last year’s Pat’s Myeloma Beach Party. I understand her and Dr. Vij’s position about the redundancy of the study. However, I think this is a worthwhile report for hem/oncs and medical oncologists that aren’t myeloma specialists. I know some of them rely on their smart phones. They locate medical standard of care and prescribe it for their patient. This study is tailor made for them. Dr. Raje doesn’t need it, but these docs who aren’t as experienced do.
Dr. Tricot realizes that upping the Kyprolis dose increases the efficacy. He also gets that it has a good shot to work for someone like me. But a medical oncologist in a town of ten thousand in West Texas or Indiana? Using Kyprolis at a higher dose than originally approved by the FDA may be news to them. The fact it might work in patients that have previously used Velcade could be news, too.
Here’s a link to the balance of Kay Jackson’s article:
Feel good and keep smiling! Pat