ASCO 2019: Dr. Rajkumar Highlights Practice-Changing Multiple Myeloma Studies

S. Vincent Rajkumar, MD, professor of medicine, consultant, Division of Hematology, Department of Internal Medicine, consultant, Division of Hematopathology, Department of Laboratory Medicine and Pathology, and 2019 Giant of Cancer Care^® in Multiple Myeloma, discussed the research surrounding multiple myeloma, including the ICARIA-MM, COLUMBA, and CASSIOPEIA studies, at the 2019 ASCO Annual Meeting.

The phase III ICARIA-MM showed that the combination of isatuximab, a novel anti-CD38 monoclonal agent, with pomalidomide (Pomalyst)/dexamethasone had improved progression-free survival (PFS) and overall response rate (ORR) compared with pomalidomide/dexamethasone alone. The combination also had a manageable safety profile, making the triplet a potential new treatment option for patients with relapsed/refractory multiple myeloma. If the isatuximab triplet gets FDA approval, it will compete with daratumumab (Darzalex), another CD38-directed monoclonal antibody, according.

“I’ve always been a fan of competitive drugs on the market which may reduce cost and reduce barriers for access,” Rajkumar said.

The phase III COLUMBA trial found that administering daratumumab subcutaneously versus the standard intravenous (IV) formulation was not inferior in patients with relapsed/refractory multiple myeloma. Currently, IV administration of daratumumab takes 4 to 6 hours and is a burden to patients, whereas subcutaneous administration only takes a few minutes, according to Rajkumar.

Part 1 of CASSIOPEIA, another phase III trial, is the first study to demonstrate clinical benefit for administering daratumumab with standard bortezomib (Velcade)/thalidomide (Thalomid)/dexamethasone in patients with transplant-eligible newly diagnosed multiple myeloma. DVTd in induction prior to and consolidation after autologous stem cell transplant (ASCT) improved the depth of response and PFS with acceptable safety. According to Rajkumar, there was also indication of an overall survival benefit, but the data are still immature.

The randomized, phase III E3A06 study compared single-agent lenalidomide (Revlimid) versus observation alone in patients with asymptomatic high-risk smoldering multiple myeloma. The ORR was 48.9% for lenalidomide and 0% for observation. Three-year PFS was 91% for lenalidomide and 66% for observation. There was no difference in the quality of life (QoL) score between arms. These data may support a change in clinical practice.

Additional promising research, according to Rajkumar, includes a study of t(11;14) in multiple myeloma in depth. Rajkumar explained that myeloma is “six or seven diseases [in] one disease…. [This study] is a start for the field to start looking at myeloma as multiple diseases.”