Medical Technology

Isatuximab added to the RVd improves response in new myeloma patients.

A brand-new drug that was recently approved for treating refractory/relapsed multiple sclerosis appears to be suitable for treating newly diagnosed patients suffering from transplant-eligible sclerosis.

The drug is called isatuximab (Sarclisa Sanofi), an anti-CD38 antibody that was approved in the last year for use in patients suffering from advanced disease.

It has been demonstrated to be beneficial for patients who are newly diagnosed with the disease. When isatuximab is added to the standard triplet therapy for myeloma it increased the likelihood that patients would be positive for the minimal residual disease (MRD) at the end of the induction phase of treatment, which increases their chances of the success of an autologous stem cells transplant (ASCT).

The new results come from the GMMG HD7 trial. All patients were treated with the triplet combination lenalidomide, bortezomib(Velcade), dexamethasone [RVd(RVd).

After randomization, some patients also received isatuximab. The MRD-negativity percentage in this group was 50.1% at induction therapy, compared to 35.6 percent for patients treated with RVd alone.

Patients who are MRD-negative at the time of ASCT have significantly better outcomes than patients who remain MRD-positive, as previously reported by Medscape Medical News.

“Isa-RVd is the first regimen to show significant MRD-negativity improvement at the end of induction versus RVd during a phase 3 trial,” reported Hartmut Goldschmidt, MD, from University Hospital Heidelberg, Germany.

He stated that the advantages of adding Isa to RVd over RVd with regard to MRD negativeness after induction therapy were consistent across all subgroups.

Goldschmidt spoke to the press prior to his presentation of data at the 2021 American Society of Hematology annual meeting.

Ravi Vij, MD from the Siteman Cancer Center in St. Louis, Missouri, said that while the results are positive, they aren’t definitive. “We need more data to determine if this represents a major breakthrough in treatment.” Vij was not part of the study.

“We know that patients who are eligible for transplant who are eligible for transplants, for whom this study was conducted,” he stated in an interview with Medscape Medical News.

He pointed out that RVd was paired with the anti-CD38 antibody. daratumumab (Darzalex) was approved in the United States for this indication in January 2021.

Vij stated that isatuximab is slow to gain acceptance in the United States because it is administered intravenously and not subcutaneously like the most recent daratumumab formulation.

He said that daratumumab is more efficient than isatuximab which can take as long as an hour and a half each infusion.

MRD vs. the CR?

Goldschmidt was asked whether MRD-negativity and complete response rates were better predictors of PFS. (PFS) during the briefing. He explained that current sequencing techniques and sensitivity down 10 -6 make it easier to determine MRD negativeity. There is a constant discussion among colleagues from the myeloma research group and the Food and Drug Administration about how to merge the data to predict PFS and overall survival.

Laurie Sehn, MD, MPH, from the BC Cancer Centre for Lymphoid Cancer in Vancouver, Canada, who was the moderator of the briefing, stated that “we’re searching for surrogate markers to speed up answers to clinical trials, and I believe that MRD in myeloma is rapidly becoming a vital surrogate marker.”

GMMG-7 Results

For their study, Goldschmidt and colleagues enrolled 662 patients with newly diagnosed multiple myeloma that were candidates for high-dose therapy as well as ASCT, and after stratification according to revised International Staging System (r-ISS) criteria randomly assigned them six three-week cycles of initial therapy using Isa-RVd and RVd by itself.

Patients were randomly assigned to maintenance using isatuximab or lenalidomide by itself after ASCT.

As we have mentioned earlier, MRD rates at induction were 50.1 percent for Isa-RVd only and 35.6 percent with only RVd. This translated into an enticing hazard ratio that favors the combination of four drugs 1.83 ( P.001).

In a multivariate study IsaRVd treatment was the only significant predictor of MRD negative. This was based on treatment group, rISS status, performance status and.

Although the rate of complete responses at the end of induction was similar between the treatment groups, the rate of very good partial response or better was higher with the isatuximab-containing combination (77.3% vs 60.5%; P < .001).

The respective rates of disease progression at end of induction in the Isa-RVd and the RVd groups were 1.5 percent and 4.0 percent.

The incidence of adverse events was generally similar across the groups, with the exception that a greater proportion of patients had leukocytopenia or neutropenia in the Isa-RVd group than the RVdgroup (26.4% vs 9.1%). There were eight deaths in the RVd group and four deaths in the IsaRVd group. The majority of deaths were attributable to COVID-19, a COVID-related disease that progresses, said Goldschmidt.

Sanofi funded the study. Sanofi funded the. Goldschmidt disclosed research grants and honoraria from Sanofi and other companies. Vij has disclosed honoraria or advisory board activities from different companies including Sanofi. Sehn is consultant and has received honoraria not from Sanofi.

ASH 2021. Abstract 463. The presentation was made on December 12, 2021.

Neil Osterweil is an award-winning medical journalist as well as a regular contributor to Medscape.

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