The main purpose of the study is to evaluate the safety and tolerability of the combination
of elranatamab and carfilzomib and dexamethasone or elranatamab and maplirpacept.

There are 2 parts to this study. Part 1 will evaluate the safety and tolerability of
elranatamab when given in combination with carfilzomib plus dexamethasone. Part 2 has 2 arms.
The first will evaluate the safety and tolerability of elranatamab when given in combination
with maplirpacept. The second will identify the optimal dose(s) of elranatamab plus
maplirpacept.

All study medicines are given over 4-week cycles. Everyone taking part in this study will
receive elranatamab as a shot under the skin. Participants in Part 1 will also receive weekly
carfilzomib as an IV infusion (given directly into a vein) and dexamethasone either by mouth
(as a pill) or by IV infusion. Participants in Part 2 will receive elranatamab in combination
with maplirpacept as an IV infusion (given directly into a vein)

The investigators will examine the experiences of people receiving the study medicines. This
will help determine if the study medicines are safe and can be used for multiple myeloma
treatment. Participants will take part in this study for about 2 years after the first dose.

This phase III trial studies how well lenalidomide and dexamethasone works with or without daratumumab-hyaluronidase in treating patients with high-risk smoldering myeloma. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Anti-inflammatory drugs, such as dexamethasone lower the bodys immune response and are used with other drugs in the treatment of some types of cancer. Daratumumab-hyaluronidase is a monoclonal antibody, daratumumab, that may interfere with the ability of cancer cells to grow and spread, and hyaluronidase, which may help daratumumab work better by making cancer cells more sensitive to the drug. Giving lenalidomide and dexamethasone with daratumumab-hyaluronidase may work better in treating patients with smoldering myeloma.

This phase III trial compares the combination of four drugs (daratumumab-hyaluronidase, bortezomib, lenalidomide and dexamethasone) to the use of a three-drug combination (daratumumab-hyaluronidase, lenalidomide and dexamethasone) in patients with newly diagnosed multiple myeloma. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Daratumumab-hyaluronidase is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Anti-inflammatory drugs, such as dexamethasone lower the bodys immune response and are used with other drugs in the treatment of some types of cancer. Adding bortezomib to daratumumab-hyaluronidase, lenalidomide, and dexamethasone may be more effective in shrinking the cancer or preventing it from returning, compared to continuing on a combination of daratumumab-hyaluronidase, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma.