To start with-Line Treatment in Freshly Diagnosed Various Myeloma
New success from a trial in individuals with newly diagnosed many myeloma provide some solutions to questions about which treatment route to pick out.
The demo, known as Willpower, discovered that newly diagnosed individuals treated with a triplet of medication had for a longer time progression-cost-free survival (PFS) if they been given an autologous stem cell transplant (ASCT) soon soon after the drug treatment than if they simply had their stem cells gathered for a attainable future transplant.
Sufferers who obtained the triplet of lenalidomide, bortezomib, and dexamethasone (RVD) in addition ASCT experienced a median PFS of 67.5 months, compared with 46.2 months for all those who received RVD but did not have a transplant soon immediately after.
Having said that, patients ended up just as probable to be alive a lot more than 6 several years immediately after cure irrespective of regardless of whether or not they underwent an quick stem cell transplant.
In addition, procedure-related adverse occasions of grade 3 or over had been increased in the group that been given the transplant right away soon after the triplet therapy.
The final results have been presented here in the course of a plenary session at the American Modern society of Scientific Oncology (ASCO) 2022 annual conference and simultaneously revealed in the New England Journal of Medicine.
“Our results validate the PFS reward of transplantation as 1st-line cure for clients with myeloma and confirms stem cell transplant as a normal of treatment with sure triplet treatment,” mentioned lead author Paul Richardson, MD, professor of medicine, Harvard Healthcare Faculty and medical software chief and director of scientific analysis at the Jerome Lipper Multiple Myeloma Heart at Dana Farber Cancer Institute, Boston, Massachusetts.
A further obtaining from the demo was that the use of upkeep lenalidomide in each teams continually till progression conferred substantial clinical reward.
“We can also say that the use of lenalidomide servicing treatment is also a normal of care,” he included.
Research Facts
In this trial, Richardson and colleagues randomly assigned 873 individuals newly diagnosed with multiple myeloma to the RVD-by yourself team (n = 357) or the transplantation group (n = 365). All people had been given a single cycle of RVD prior to randomization and then been given two additional RVD cycles as well as stem-mobile mobilization followed by either 5 more RVD cycles (the RVD-alone group) or large-dose melphalan as well as ASCT followed by two additional RVD cycles (the transplantation team). Lenalidomide was administered to all individuals till disease progression, unacceptable side results, or both equally.
At a median adhere to-up of 76. months, the threat of condition progression or demise was 53% larger between individuals who gained RVD by yourself vs . the transplantation team (hazard ratio [HR], 1.53 P < .001). The median duration of PFS among patients with a high-risk cytogenetic profile was 55.5 vs 17.1 months, favoring the transplantation group.
The percentage of patients who were alive without progression at 5 years was 58.4% vs 41.6%, respectively (HR, 1.66) and median duration of response was 56.4 vs 38.9 months, also favoring transplantation (HR, 1.45).
The estimated 5-year overall survival was similar between groups: 80.7% for transplantation and 79.2% for RVD alone (HR for death, 1.10 P> .99). For people with a significant-hazard cytogenetic profile, 5-calendar year survival was 63.4% compared to 54.3%, respectively.
“This tells us that for sufferers who experienced kept transplant in reserve, they experienced the exact same overall survival as those people who had experienced a transplant correct absent, in spite of there remaining these types of remarkable first disorder command for the patients in whom transplant was utilised early,” Richardson commented in a push launch from his institution.
Individuals who did not undertake rapid transplant obtained treatment when their disease progressed with more recent and lively therapies, this kind of as monoclonal antibodies and/or following-generation novel brokers, he famous. Only 28% of individuals made use of the reserve choice of a transplant.
“It demonstrates the extent to which sufferers now have possibilities and that we have new info to information them in balancing the pluses and minuses of each method,” he additional.
When seeking at protection, the authors observed that the most common remedy-associated adverse events of quality 3 or greater happened in 279 patients (78.2%) in the RVD-by itself team and 344 sufferers (94.2%) in the transplantation team. Of those individuals, 60.5% and 89.9%, respectively, documented hematologic gatherings of quality 3 or greater (P < .001). The 5-year cumulative incidence of invasive second primary cancers was similar in both cohorts (RVD-alone group, 4.9% transplantation group, 6.5%).
However, while the risk of secondary cancers was similar between groups, Richardson noted that there was a higher incidence of acute myeloid leukemia and myelodysplastic syndromes in the transplant cohort.
“There was also a significant drop in quality of life across transplant procedures, but the good news is that it was recoverable rapidly,” he said. “What is also really important is that we have prospective, multicenter, national comparative data on toxicity. That’s very important for providing patients with a choice as they move forward with their treatment plan.”
He also noted that treatment continues to evolve. “This study was designed in 2009, begun in 2010, and now there is mature data in 2022,” Richardson commented. “This is particularly relevant as we have now further improved the induction treatment for younger patients with newly diagnosed myeloma using quadruplet regimens incorporating monoclonal antibodies and novel next-generation therapies. The results from these studies are extremely exciting.”
“Now more than ever, treatment for multiple myeloma can be adapted for each patient,” Richardson commented. “Our study provides important information about the benefits of transplant in the era of highly effective novel therapies and continuous maintenance, as well as the potential risks, to help patients and their physicians decide what approach may be best for them. This is particularly relevant as we have now further improved the induction treatment for younger patients with newly diagnosed myeloma using quadruplet regimens incorporating monoclonal antibodies, such as RVD combined with daratumumab.”
Lack of Difference in Overall Survival
These new results further support an already established role of autologous hematopoietic stem cell transplantation in the management of patients with multiple myeloma, said Samer Al-Homsi, MD, MBA, clinical professor of medicine and director of the blood and marrow transplant program at Perlmutter Cancer Center, NYU Langone, New York City, who was approached for comment.
“The treatment regimen is applicable to patients who are determined by an expert in transplantation to be fit to receive autologous hematopoietic transplantation,” he added. “Although this study, like many others, establishes hematopoietic stem cell transplantation as part of the standard of care in multiple myeloma, only a fraction of patients are actually offered this important modality of treatment for a variety of reasons, including provider bias,” he noted. “In fact, although improvement in supportive care has enhanced the safety of the procedure, many patients are denied this therapy.”
Al-Homsi also noted that the lack of difference in overall survival might be due to the fact that some patients (28%) in the RVD alone group did end up undergoing transplantation at the time of progression. “Also, longer follow-up might reveal a difference in overall survival,” he said.
The toxicities are manageable, and the incidence of secondary malignancies was not significantly different between cohorts. “However,” he emphasized, “lenalidomide has been associated in other studies with increased incidence of secondary malignancies and it must be noted that this study used extended administration of lenalidomide until progression.”
Support for this study was provided by grants to the Blood and Marrow Transplant Clinical Trials Network from the National Heart, Lung, and Blood Institute, the National Cancer Institute, R. J. Corman Multiple Myeloma Foundation, Celgene/Bristol Myers Squibb, and Millennium/Takeda Pharmaceutical. Richardson has reported relationships with Celgene, Janssen, Jazz Pharmaceuticals, Karyopharm Therapeutics, Oncopeptides, Sanofi, Secura Bio, Takeda, and Bristol Myers Squibb. Al-Homsi has reported no relevant financial relationships.
ASCO 2022. Abstract LBA4. Presented June 5, 2022
N Engl J Med. Published online June 5, 2022. Full text
For more from Medscape Oncology, join us on Twitter and Facebook.