HemOnctoday posted an excellent review of the new, state of the art anti-myeloma induction therapy using a combination of Revlimid, Velcade and dexamethasone (RVD) last week. The article features a number of well known myeloma experts and is quite long.
Toward the end of the article, yesterday’s topic about whether to continue using stem cell transplant (SCT) as a standard of care for newly diagnosed patients is also discussed.
HemOnctoday is a members only, medical publication designed for physicians. But I found this article to be easy to follow. Here is the first part of the post, written by Cassandra Richards, followed by the concluding discussion about SCT:
Impressive response rate seen with three-drug regimen for multiple myeloma
For the first time ever, a three-drug regimen resulted in a 100% response rate and a favorable tolerability profile in patients with multiple myeloma, according to new findings.
The combination of lenalidomide (Revlimid, Celgene), bortezomib (Velcade, Millennium Pharm) and dexamethasone proved highly effective for previously untreated multiple myeloma, and these findings may change future standards of care in this setting, the investigators reported in their study recently published in Blood.
There are numerous exciting upfront treatment options that appear to be promising, said the study’s lead author, Paul G. Richardson, MD, clinical director, Jerome Lipper Center for Multiple Myeloma at Dana-Farber Cancer Institute and associate professor of medicine, Harvard Medical School, Boston.
Paul G. Richardson, MD and colleagues are evaluating the benefit of early autologous stem cell transplantation combined with the three-drug regimen for multiple myeloma.
“The bortezomib/lenalidomide combination is especially exciting because of the depth and quality of response, together with a manageable tolerability profile,” Richardson told HemOnc Today. “The bottom line is that the bortezomib-based or lenalidomide-based therapies show the greatest promise in my view, with the combination of the two generating the best results to date in several studies.”
The phase 1/2 study was the first prospective multicenter investigation of the lenalidomide/bortezomib/dexamethasone regimen, otherwise known as RVD, in newly diagnosed multiple myeloma patients. In addition to showing impressive activity in treated patients, RVD also demonstrated favorable tolerability over a lengthy period with no treatment-related mortality.
Patients received 3-week cycles of bortezomib dosed between 1 mg/m2 or 1.3 mg/m2 on days 1, 4, 8 and 11; lenalidomide 15 mg to 25 mg on days 1 to 14; and dexamethasone 40 mg or 20 mg given on the day of and day after bortezomib. Responding patients received maintenance therapy with weekly bortezomib and lenalidomide given on the same 2-week-on, 1-week-off schedule, or proceeded to transplantation, according to physician and patient choice. Phase 2 dosing was determined to be bortezomib 1.3 mg/m2, lenalidomide 25 mg and dexamethasone 20 mg.
The rate of partial response was 100% in both the phase 2 population and overall, with 74% and 67% each achieving very good partial response or better. Complete or near-complete response was seen in 54% of patients treated at the phase 2 dosing. Twenty-eight patients (42%) subsequently underwent transplantation successfully and without any unusual events reported.
The median length of follow-up was 21 months, with an estimated 18-month PFS and OS for the combination treatment with/without transplantation of 75% and 97%, respectively.
Now let’s jump ahead to the discussion about SCT:
Is transplant still necessary?
The goal of frontline therapy for multiple myeloma is complete remission and/or long-term disease control. While most centers in the United States offer transplant to younger patients, the issue of whether autologous stem cell transplantation contributes to the depth and duration of remission is being evaluated by Richardson and colleagues. The trial is designed to determine whether the new drug combination of RVD will benefit from early transplant or be sufficient with transplant being kept in reserve, Stewart said.
“I think that most people still think that auto transplant would be a standard of care and would automatically consider recommending it for a patient under 65 years,” Durie said. “We don’t know that in the era of novel agents. What is the added value of doing an auto transplant for someone who is already in a complete remission with something like Velcade, Revlimid and dexamethasone, for example? That combination is a top-of-the-line sort of treatment that some consider has the best response rate as a first-line choice.”
Although some patients may be considered eligible for transplant, the patient and/or clinician may not choose that treatment. Durie said the most recent numbers for the United States show that only one-third of eligible patients actually proceed with transplantation.
“That’s partly a physician preference in that the other treatments have improved so much that it’s not an absolute necessity,” he said. “Also, the patient must be considered. A transplant does help achieve a better response with drug therapy but it does not guarantee a longer remission. So many patients are willing to stay on drug therapy without transplant.”
Well done, Cassandra! Go to: Impressive response rate seen with three-drug regimen for multiple myeloma to read a candid exchange about therapy philosophies between Dr. James Berenson, Dr. Brian Durie, Dr. Kieth Stewart and Dr. William Bensinger. Good stuff!
Feel good and keep smiling! Pat