[News Focus] Immunotherapies emerge as new blood cancer drugs

ATLANTA, Ga. -- By Kim Yun-mi/Korea Biomedical Review correspondent - Transplantation and chemotherapy used to be the standard treatment for lymphoma and myeloma, but immunotherapies including CAR-T therapy, bispecific antibodies, and monoclonal antibodies are being developed quickly to treat blood cancer.

At the American Society of Hematology (ASH 2021) meeting, being held at the Georgia World Congress Center in Atlanta, Georgia, from Saturday to Tuesday this week, four studies of immunotherapies have been selected to be introduced in the plenary and late-breaking session.

The American Society of Hematology holds an annual meeting at the Georgia World Congress Center in Atlanta, Ga., the U.S., from Saturday to Tuesday this week.

Immunotherapy refers to a treatment utilizing the patient’s immune system to kill cancerous cells.

The development of monoclonal antibodies, antibody-drug conjugates (ADC), and immune checkpoint inhibitors have raised the level of solid cancer treatment one notch.

However, it is quite recent that hematologists started to use immunotherapy to treat blood cancer.

The four studies of immunotherapies that the ASH paid attention to have a different mechanism of action, but they focus on non-Hodgkin’s lymphoma that affects white blood cells and multiple myeloma (MM) that affects plasma cells.

Sarclisa shows potential as 1st-line standard care for MM

The phase 3 GMMG-HD7 trial investigated Sanofi’s anti-CD38 monoclonal antibody Sarclisa (isatuximab) for the treatment of MM.

Sarclisa has been used to treat recurrent/refractory MM.

The latest study was used in combination with RVd -- lenalidomide, bortezomib, and dexamethasone – in patients with transplant-eligible MM. It showed that it could achieve minimal residual disease (MRD) negativity.

The study included 662 patients from 67 sites in Germany.

The results showed that half (50.1 percent) of patients who received the Sarclisa+RVd regimen for 18 weeks achieved MRD negativity, versus 35.6 percent of the conventional RVd therapy.

Professor Hartmut Goldschmidt of the Heidelberg University Hospital and National Center of Tumor Diseases Heidelberg in Germany, who led the study, said isatuximab works in two ways -- direct effects of antibodies on myeloma cells and immune stimulation.

The study started from an idea that isatuximab could be more effective in treating myeloma if it stimulates the immune system, he said.

“This study is the first phase 3 trial that challenged the standard therapy widely used in the U.S. and Europe and achieved success,” Goldschmidt said. “The results showed that this treatment (Sarclisa+RVd) could be a new standard of care in newly diagnosed, transplant-eligible MM patients.”

According to Goldschmidt, the GMMG-HD7 trial is ongoing. Later, the researchers will evaluate Sarclisa+RVd versus RVd after autologous stem cell transplantation and the potential of maintenance therapy using Sarclisa with lenalidomide.

Mosunetuzumab shows chance to improve recurrent/refractory follicular lymphoma

The second study that the ASH focused on was data from a phase 1/2 trial of mosunetuzumab, a CD3/CD20 targeting bispecific antibody being developed by Roche.

Mosunetuzumab monotherapy in patients with relapsed/refractory follicular lymphoma (FL) who had been previously treated twice or more showed deep and lasting remission maintenance.

In the study, 80 percent of 90 patients responded to mosunetuzumab during a follow-up period of 18 months or more, and 60 percent showed a complete response (CR), suggesting mosunetuzumab’s strong effect.

Elizabeth Budde, an oncologist and associate professor at City of Hope Comprehensive Cancer Center, who led the study, said mosunetuzumab was a bispecific antibody designed to recognize and bind both lymphoma cells and the patient's own immune T cell targets.

She explained that mosunetuzumab was a very effective and safe drug for patients who did not respond to conventional therapies.

“This study outcome provides strong evidence for the treatment’s unique mechanism of action.”

According to Budde, unlike CAR-T cell therapy, mosunetuzumab could be given directly into the bloodstream without removing or modifying the patient’s immune cells before drug administration.

Just like in CAR-T cell therapy, 44.4 percent of mosunetuzumab-treated patients experienced cytokine release syndrome (CRS). However, except for two cases, all the events were low-grade adverse reactions, recoverable and manageable, she said.

“The goal of the treatment is not only treating lymphoma but improving the patient’s quality of life,” Budde said. “Mosunetuzumab will offer a chemotherapy-free treatment opportunity by helping the patient’s immune system to recognize lymphoma cells.”

CAR-T cell therapy Breyanzi could work in 2nd-line large B-cell lymphoma

BMS’ CAR-T cell therapy Breyanzi (lisocabtagene maraleucel) and Gilead’s Yescarta (axicabtagene ciloleucel) were in the spotlight, proving their potential as the new second-line standard treatment for large B-cell lymphoma.

The TRANSFORM trial of Breyanzi and ZUMA-7 of Yescarta showed that the new treatment was effective with just one administration in relapsed large B-cell lymphoma, compared to conventional chemotherapy and transplantation. The studies signaled that there would be a breakthrough in the treatment paradigm in large B-cell lymphoma.

The TRANSFORM study compared Breyanzi with the existing standard therapy in 184 transplant-eligible patients with relapsed or refractory large B-cell lymphoma. The Breyanzi-treated group proved superiority in event-free survival, the primary endpoint.

The medial FDS of the Breyanzi treatment group was 10.1 months, compared with 2.3 months of the standard therapy group.

The company said that the complete response of the Breyanzi group was 66 percent, significantly high compared to 39 percent of the standard therapy group.

Among 92 patients randomly assigned to the standard therapy group, 50 patients crossed over to the Breyanzi group.

Manali Kamdar, the lead investigator at the University of Colorado Cancer Center, said the current standard of care consisting of chemotherapy and stem cell transplant is ineffective in treating patients with relapsed or refractory large B-cell lymphoma was a high unmet need.

Despite a relatively short follow-up period of just over six months, the study outcome was positive.

“This indicates that CAR-T cell therapy could become a new standard therapy for patients who do not respond to early chemotherapy or relapse within a year,” he said.