Isatuximab confers ‘impressive’ delay in multiple myeloma progression
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Key takeaways:
- Isatuximab plus a standard care regimen improved PFS among certain older individuals with multiple myeloma.
- Adding isatuximatb to the standard care regimen significantly improved response rates.
CHICAGO — Isatuximab combined with a standard first-line treatment regimen significantly reduced the risk for disease progression and death in certain older individuals with multiple myeloma, results from a randomized phase 3 study showed.
Additionally, patients with newly diagnosed, transplant-ineligible disease treated in the isatuximab (Sarclisa, Sanofi) arm of the IMROZ trial had superior PFS and response rates, including minimal residual disease (MRD) complete responses, according to findings presented at ASCO Annual Meeting and simultaneously published in The New England Journal of Medicine
“I think it will become a standard of care,” Thierry Facon, MD, professor of hematology at Lille University Hospital in France, told Healio.
“If you ask the same question to my U.S. colleagues, they will tell you that quadruplet regimens having a CD38 [monoclonal antibody], a proteasome inhibitor and an immunomodulatory agent are already standard of care for many patients in the U.S.,” he added. “That’s true for transplant-eligible patients. That’s true for younger patients, and that will become true — to a certain extent — for elderly patients as well.”
Background and methodology
New diagnoses of multiple myeloma surpass 180,000 globally every year, making it the second most common hematologic malignancy, according to data compiled by the International Agency for Research on Cancer.
Fonseca and colleagues published findings in BMC Cancer showing that individuals with multiple myeloma have a 5-year survival rate of just 52%.
Healio previously reported isatuximab, a CD38-directed monoclonal antibody, has improved outcomes for patients with transplant-eligible multiple myeloma.
Also, at ASH Annual Meeting last year, a presentation on the IsKia trial indicated isatuximab, in combination with carfilzomib, lenalidomide and dexamethasone, increased rates of MRD negativity.
“The purpose of the IMROZ study was to assess the clinical benefit of isatuximab in combination with [bortezomib, lenalidomide and dexamethasone (VRd)] in transplant-ineligible patients,” Facon said. “The IMROZ study is the first large phase 3 international study combining a CD38 monoclonal antibody on the VRd, and the VRd is a very well-known and very well-accepted standard of care for both transplant-eligible and transplant-ineligible patients.”
The open-label trial enrolled 446 adults aged 55 to 80 years (median age, 72), with 30% of the patient population aged 75 to 80 years, Facon said.
Researchers randomly assigned study participants in a 3:2 ratio to either the isatuximab treatment arm or control arm.
Patients in the treatment arm received four 6-week cycles of isatuximab with VRd and then continuous treatment of isatuximab, lenalidomide and dexamethasone. The control arm received the same therapies without isatuximab.
Facon and colleagues evaluated PFS as the study’s primary endpoint, with secondary endpoints that included complete response rate, MRD negativity for those who achieved complete response and OS, among others.
Results and next steps
Individuals in the treatment arm had more than a 40% decrease in disease progression and death compared with those in the control group (HR = 0.596; 98.5% CI, 0.406-0.876) at a median follow-up of 59.7 months.
Patients who received isatuximab did not reach median PFS, whereas those treated with standard VRd had a median PFS of 54.3 months.
Complete responses occurred in 74.7% of participants in the treatment arm and 64.1% in the control group (OR = 1.7; 95% CI, 1.09-2.5).
In the isatuximab group, 55.5% of patients had MRD-negativity and a complete response compared with 40.9% of patients in the control group (OR = 1.8; 95% CI, 1.22-2.64).
Also, 46.8% of individuals in the treatment arm had MRD negativity for at least 1 year compared with 24.3% in the standard VRd group (OR = 2.7; 95% CI, 1.79-4.14).
Nearly double the number of individuals in the isatuximab cohort remained on treatment as of the study’s data cutoff date compared with the control group (47.2% vs. 24.3%).
“I would say that the study results exceeded my expectations.” Facon said. “The PFS results are quite impressive.”
More patients in the treatment arm had grade 3 or worse treatment-related adverse events compared with the control arm (91.6% vs. 84%). Common adverse events included neutropenia, diarrhea, peripheral neuropathy, cataracts and infections, including pneumonia, and researchers observed more adverse events in patients aged 70 years and up, Facon said.
However, that “was consistent with the safety profile of each drug. Nothing was new and nothing was unexpected,” Facon said. “For example, neurological toxicity is related to bortezomib, cataracts are related to the long-term use of dexamethasone, and, of course, infections remain quite a usual complication with any kind of myeloma regimen.”
Facon also noted the significantly longer treatment duration for the isatuximab group (53.2 months vs. 31.3 months).
“The median number of cycles was 29 for VRd vs. 52 for isatuximab VRd,” he said. “When you look at safety, you also have to look at treatment exposure. You have to investigate exposure-adjusted incidence rates, and these exposure-adjusted incidence rates were quite similar in in both arms.”
The FDA granted isatuximab in combination with VRd priority review for treatment of patients with newly diagnosed multiple myeloma on May 27.
Future research could investigate if this regimen, or a different version of it, could work for individuals aged 80 years and older.
“Along with studies in transplant-eligible patients, IMROZ, conducted in certain elderly patients, is an important step forward in favor of these quadruplet regimens,” Facon said.
References:
- Facon T, et al. Abstract 7500. Presented at: ASCO Annual Meeting; May 31-June 4, 2024.
- Fonseca R, et al. BMC Cancer. 2020;doi:10.1186/s12885-020-07503-y.
- Gay F, et al. Blood. 2023;doi:10.1182/blood-2023-177546.
- Facon T, et al. New England Journal of Medicine. 2024;doi:10.1056/NEJMoa2400712
- International Agency for Research on Cancer. Global Cancer Observatory: Cancer today. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/35-multiple-myeloma-fact-sheet.pdf. Accessed May 31, 2024.
For more information:
Thierry Facon, MD, can be reached at thierry.facon@chu-lille.fr.
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Facon T, et al. Abstract 7500. Presented at: ASCO Annual Meeting; May 31-June 4, 2024: Chicago.
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